• Availability of an eligible haploidentical donor
• Hematologic malignancy or solid tumor
• Patients with more than one malignancy (hematologic or solid tumor) are eligible
• Patients with hematologic malignancy must have no HLA identical sibling or suitable unrelated donor OR time needed to find an acceptable unrelated donor match would likely result in disease progression such that the patient may become ineligible for any type of potentially curative transplant
• Relapsed or primary therapy-refractory AML with bone marrow blast < 20%
• High-risk refractory or relapsed ALL in patients for whom transplantation is deemed indicated (relapse occurring < 30 months from diagnosis, patients relapsing after previous allogeneic transplant, relapse after 2nd remission, primary induction failure or hypodiploidy)
• Relapsed Hodgkin lymphoma unable to achieve 2nd remission or Very Good Partial Response (VGPR) and therefore ineligible to receive autologous hematopoietic stem cell transplant (auto-HSCT)
• Hodgkin lymphoma relapsing after auto-HSCT
• Primary refractory or relapsed non-Hodgkin lymphoma unable to achieve 2nd remission or VGPR and therefore ineligible to receive auto-HSCT
• Non-Hodgkin lymphoma relapsing after auto-HSCT
• Myelodysplastic Syndrome/Myeloproliferative Syndrome Solid Tumor
• Patients with solid tumor must have failed or have been ineligible to receive auto-HSCT or if auto-HSCT would not offer > 20% chance of cure
• Neuroblastoma
• high risk with relapsed or refractory disease
• Soft tissue sarcomas (Rhabdomyosarcoma, Ewing sarcoma, Primitive Neuroectodermal Tumor or other high-risk extracranial solid tumors)
• Relapsed or primary refractory metastatic
• 1st complete remission, but very high-risk features (i.e., < 20% survival with conventional therapy)
• Osteosarcoma
• Failure to achieve Complete Response (CR) following initial therapy
• Relapsed with pulmonary or bone metastases and did not achieve a CR with surgery and/or chemotherapy
• Karnofsky (patients > 16 years) or Lansky (patients 16 years or older) performance score of ≥ 60
• Life expectancy of ≥ 3 months
• Patient must have fully recovered from acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Study enrollment no earlier than 3 months after preceding HSCT
• Glomerular Filtration Rate (GFR) ≥ 60 ml/min/1.73m2
• Total bilirubin < 3 mg/dL
• ALT (alanine aminotransferase, SCPT) ≤ 5 x Upper LImit of Normal (ULN) for age
• Ejection fraction of > 40% by Multigated Acquisition Scan (MUGA) or echocardiogram
• No evidence of dyspnea at rest
• No supplemental oxygen requirement
• If measured, carbon monoxide diffusion capacity (DLCO) >50%
• No severe peripheral neuropathy, signs of leukoencephalopathy or active Central Nervous System (CNS) infection
• Patients with seizure disorders may be enrolled if seizures are well controlled on anticonvulsant therapy
• If of reproductive potential, negative pregnancy test and willing to use effective birth control method
• Informed consent from patient or legal guardian (if patient is minor) Inclusion Criteria for Donors:
• Donor must be 18 years of age minimum, 65 years of age maximum
• Donor must be in good general health as determined by evaluating medical provider
• Must meet donor criteria for human cells, tissues, and cellular and tissue-based products per Code of Federal Regulations 21 CFR 1271, subpart C. Specifically:
• Donor screening in accordance with 1271.75 indicates that the donor:
• Is free from risk factors for, and clinical evidence of, infection due to relevant communicable disease agents and diseases; and
• Is free from communicable disease risks associated with xenotransplantation; and
• The results of donor testing for relevant communicable disease agents in accordance with 1271.80 and 1271.85 are negative or nonreactive, except as provided in 1271.80(d)(1).
• Haploidentical by HLA-typing
• Preference will be given to donors who demonstrate KIR incompatibility with recipient HLA class I ligands defined as the donor expressing a KIR gene for which the corresponding HLA class I ligand is not expressed by the recipient.
• Negative testing for relevant communicable diseases:
• Hepatitis B surface antigen (HBsAg)
• Hepatitis B core antibody (Anti-HBc)
• Hepatitis C antibody (Anti-HCV)
• HIV 1 & 2 antibody (Anti-HIV-1, 2 plus O)
• HTLV I/II antibody (Anti-HTLV I/II)
• RPR (Syphilis TP)
• CMV (Capture CMV)
• MPX for: HepB (HBV-PCR), HepC (HCV-PCR), HIV (HIV-PCR)
• NAT for West Nile Virus (WNV-PCR)
• T. Cruzi
•EIA (Chagas)
• Pregnant or breast-feeding
• HIV infection
• Heart failure or uncontrolled cardiac rhythm disturbance
• Uncontrolled, Serious Active Infection
• Prior organ allograft
• Significant serious intercurrent illness unrelated to cancer or its treatment not covered by other exclusion criteria expected to significantly increase the risk of HSCT
• Any mental or physical condition, in the opinion of the PI (or PI designee), which could interfere with the ability of the subject (or the only parent or legal guardian available to care for the subject) to understand or adhere to the requirements of the study
• Enrollment in any other clinical study from screening up to Day 100 (unless PI judges such enrollment would not interfere with endpoints of this study) Exclusion Criteria for Donors:
• Lactating females
• Pregnant females

Major
• Able to understand and comply with study procedures, understand the risks involved, and provide written informed consent.
• For Phase 1, histologically and / or cytological confirmed unresectable or metastatic solid malignancy, refractory to standard therapies with no more than three prior lines of therapy (Completed).
• For Phase 2, seven cohorts will be enrolled: Cohort A-1: NSCLC EXON 14 skip mutation (c-Met naïve) for first line treatment, Cohort A-2: NSCLC EXON 14 skip mutation (c-Met naïve) pretreated subjects with no more than 3 lines of prior therapy, Cohort B: NSCLC EXON 14 skip mutation (c-Met experienced; radiographic progression on prior c-Met inhibitor), Cohort C: basket of tumor types with c-Met high level amplification (except Primary CNS tumors), Cohort C-1: NSCLC harboring MET amplification and wild-type epidermal growth factor receptor (EGFR) with no more than 3 lines of prior therapy (MET Naive), Cohort D: basket of tumor types except for primary CNS tumors harboring MET gene fusions (e.g., NSCLC, upper GI, colorectal, hepatobiliary cancer). Previously treated; or previously untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines in unresectable or metastatic setting). Met naive, Cohort E: Primary CNS tumors with MET alterations (single or co-occurred MET fusion including PTPRZ1-MET [ZM] fusion, MET Exon 14 skipping mutation, or MET amplification).Previously treated or previously untreated but refused standard treatment, or if treatment was unavailable or unfeasible (≤ 3 prior lines), Met naive.
•Local/archival result (tissue and/or plasma) of a positive c-Met dysregulation is required (except in Cohort A-1 in the US and Cohort C-1). In Phase 2, provision of either archival or a fresh tumor biopsy sample (if safe and feasible) either from the primary or a metastatic site is required for study entry for Cohorts A-1, A-2, C, C-1, and D.
• Measurable disease according to relevant criteria (RECIST v1.1, RANO for CNS tumors, or other relevant criteria per tumor type).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and/or Karnofsky Performance Scale (KPS) score.
• For all prior anticancer treatment, including radiotherapy, chemotherapy or targeted agents or hormonal therapy, a duration of more than 30 days or 5 half-lives of the agents used, whichever is shorter, must have elapsed, and any encountered toxicity must have resolved to levels meeting all the other eligibility criteria prior to the first dose of study treatment. Palliative radiotherapy to non-target lesions should be completed within 2 weeks prior to APL-101 administration.
• No planned major surgery within 4 weeks of first dose of APL-101
• Expected survival (life expectancy) ≥ 3 months from C1D1. Major
• Hypersensitivity to APL-101, excipients of the drug product, or other components of the study treatment regimen.
• Known actionable mutation/gene rearrangement of EGFR (except for Cohort C), ALK, ROS1, RET, NTRK, KRAS, and BRAF.
• Unstable angina or myocardial infarction within 1 year prior to first dose of APL-101, symptomatic or unstable arrhythmia requiring medical therapy, history of congenital prolonged QT syndrome, prolonged QT interval corrected by Fridericia formula (QTcF) at screening (> 450 msec based on the average of 3 measurements), or concurrent treatment with a medication that is a known risk for prolonging the QT interval.
• Unable to swallow orally administered medication whole.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., Crohn's, ulcerative colitis, active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome). Symptomatic and/or neurologically unstable CNS metastases, or who require an increase in steroid dose to control CNS disease. Subjects who have been receiving a stable steroid dose for at least 2 weeks prior to C1D1 may be allowed.
•Women who are breastfeeding.

• Subjects must be ≥ 18 years of age.
• Subjects must have histologically documented solid tumors (including lymphoma and multiple myeloma).
• Specific criteria for individual tumor types are as follows: 1. Participants with gliomas are eligible at any stage of disease 2. Participants with pancreatic carcinoma are eligible at any stage of disease 3. Participants with rare tumors (i.e. cancer started in an unusual place in the body, it is unusual type and requires special treatment) are eligible at stages II-IV. 4. Participants with other tumor types must have recurrent, relapsed, refractory, metastatic, or advanced stages III or IV cancer.
• Must have an adequate formalin-fixed paraffin-embedded tumor specimen for genomic sequencing.

• Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation
• Unresectable or metastatic disease
• Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts
• Adequate organ function
• History of intestinal disease or major gastric surgery or inability to swallow oral medications
• Other active cancer

• APEC1621SC: Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621A based on the presence of an actionable mutation as defined in APEC1621SC
• Patients must be >= than 12 months and =< 21 years of age at the time of study enrollment
• Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT; Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; Note: neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required time frame, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil [ANC] counts): >= 7 days after the last dose of agent; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor leukocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, NK cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial brain metastases (BM) radiation; Note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to other NTRK inhibitors including but not limited to LOXO-101 (larotrectinib), entrectinib (RXDX-101), DS6051, PLX7486
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment)
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment) or
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL); male: 0.6 female: 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL); male: 0.8 female: 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL); male: 1 female: 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL); male: 1.2 female: 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL); male: 1.5 female: 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL); male: 1.7 female: 1.4
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment); (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Patients with seizure disorder may be enrolled if on anti-convulsants and well controlled
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflect (DTR); any grade of DTR is eligible
• All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease (GVHD) post bone marrow transplant are not eligible for this trial
• Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study; Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
• Patients who have received prior therapy with a specific inhibitor of TRK (including but not limited to entrectinib [RXDX-101], DS-6051b, and PLX7486) are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

• Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621D based on the presence of an actionable mutation as defined in APEC1621SC; note that treatment assignment may be to primary cohort A for patients with TSC1 or TSC2 loss of function mutations or primary cohort B for patients with other PI3K/MTOR pathway mutations
• Patients accruing to dose level 1 must have a body surface area >= 0.52 m^2 at the time of study enrollment; patients accruing to dose level 2 must have a body surface area >= 0.37 m^2 at the time of study enrollment; patients accruing to dose level -1 must have a body surface area >= 0.75 m^2 at the time of study enrollment
• Patients must have radiographically measurable disease at the time of study enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Bone lesions without an associated soft tissue mass >= 10 mm in greatest diameter; bone lesions with an associated soft tissue mass >= 10 mm in greatest diameter imaged by CT or MRI are considered measurable
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive; >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 [131I-MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to LY3023414
• Patients must not have received prior exposure to an agent specifically directed at the PI3K/MTOR pathway (a PI3K inhibitor, an AKT inhibitor, an MTOR inhibitor, including rapalogs, or a combined PI3K/MTOR inhibitor)
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L; (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL
• Patients must have a normal blood sugar level for age; if an initial random draw (i.e. non-fasting) blood glucose value is out of range, it is acceptable to repeat this test as a fasting draw
• Patients must have a serum triglyceride level =< 300 mg/dL and serum cholesterol level =< 300 mg/dL; if an initial random draw (i.e. non-fasting) is out of range, it is acceptable to repeat this test as a fasting draw
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
• Nervous system disorders (by Common Terminology Criteria for Adverse Events version 5.0 [CTCAE V 5.0]) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR); any grade of DTR is eligible
• Corrected QT (QTc) interval =< 480 milliseconds
• Patients must be able to swallow intact tablets
• All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
• Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while receiving study treatment and for 3 months after the last dose of LY3023414
• Concomitant medications
• Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients who are currently receiving another investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who have an uncontrolled infection are not eligible
• Patients who have insulin dependent diabetes are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients with subependymal giant cell astrocytomas (SEGAs) are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

• Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F based on the presence of an actionable mutation
• Patients must be >= than 12 months and =< 21 years of age at the time of study enrollment.
• Patients must have a body surface area >= 0.5 m^2 at enrollment
• Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on a standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age
• Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell Infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial none marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to ensartinib; prior treatment with other ALK inhibitors is permitted given that at least 5 half-lives or 21 days have elapsed since therapy discontinuation, whichever is greater
• For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment)
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for female
• Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for female
• Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for female
• Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL for female
• Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL for female
• Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for female
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Patients must be able to swallow intact capsules
• All patients and/or their parents or legally authorized representatives must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines
• Pregnant or breast-feeding women will not be entered on this study because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study treatment and for one week after the last dose of ensartinib
• Concomitant medications
• Corticosteroids: patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients who are currently receiving another investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• CYP3A4 agents: patients who are currently receiving drugs that are strong inducers or strong inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study
• Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

• Subjects must be able to understand the nature of this trial and provide written informed consent, prior to any study specific procedures; patients with Impaired Decision Making Capacity (IDMC) who have a close caregiver or legally authorized representative (LAR) may be considered eligible for this study at the treating physician's discretion, provided that the physician is reasonably sure that the possible risks and benefits of the study are clear and that the patient will take the drug as prescribed
• Subjects must be diagnosed with a glioma, cholangiocarcinoma or other solid malignant tumor that has progressed despite standard therapy, or for which no effective standard therapy exists, with biopsy-confirmed evidence of an IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins; patients must have IDH1 or IDH2 mutation which must be detected in a clinical accredited laboratory using a Food and Drug Administration (FDA)-approved molecular test or a validated deoxyribonucleic acid (DNA)-based assay conducted in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; only specific mutations that lead to a neomorphic phenotype will be eligible for enrollment, and include IDH1: R132V, R132G, R132S, R132L, R132C and R132H; IDH2: R140W, R140L, R140Q, R172W, R172G, R172S, R172M, R172K
• Patients must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies (with a third biopsy upon evidence of disease progression); in case of multiple lesions, tumor biopsies will be performed on the most accessible site of disease; all possible precautions to avoid complications will be taken, including discussions in multidisciplinary meetings, if needed; patients affected by glioma will not be considered for study biopsies
• Patients must be willing to undergo extra blood sampling for correlative studies
• Subjects with extracranial disease must have evaluable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); subjects affected by glioma must have evaluable disease by Response Assessment in Neuro-Oncology Criteria (RANO) criteria
• For subjects with glioma, specific inclusion criteria are as follows:
• The disease should be recurrent or transformed glioma; subjects must not have had prior surgery (biopsy allowed) or radiation therapy within 3 weeks of enrollment
• There must be an enhancing component of disease, as evaluated on pre-treatment magnetic resonance imaging (MRI)
• For patients with World Health Organization (WHO) grade III or IV glioma and progressive disease < 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria:
• New enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line)
• If there is unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor areas. i.e., > 70% tumor cell nuclei in areas), high or progressive increase in MIB-1 proliferation index compared with prior biopsy, or evidence for histologic progression or increased anaplasia in tumor);
• Note: Given the difficulty of differentiating true progression from pseudoprogression, clinical decline alone, in the absence of radiographic or histologic confirmation of progression, will not be sufficient for definition of progressive disease in the first 12 weeks after completion of concurrent chemoradiotherapy
• For patients with WHO grade III or IV glioma and progressive disease >= 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria:
• New contrast-enhancing lesion outside of radiation field on decreasing, stable, or increasing doses of corticosteroids
• Increase by >= 25% in the sum of the products of perpendicular diameters between the first post-radiotherapy scan, or a subsequent scan with smaller tumor size, and the scan at 12 weeks or later on stable or increasing doses of corticosteroids
• For patients receiving antiangiogenic therapy, significant increase in T2/fluid attenuated inversion recovery (FLAIR) non-enhancing lesion may also be considered progressive disease; the increased T2/FLAIR must have occurred with the patient on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy and not be a result of comorbid events (e.g., effects of radiation therapy, demyelination, ischemic injury, infection, seizures, postoperative changes, or other treatment effects)
• Note: Clinical deterioration alone is not attributable to concurrent medication or comorbid conditions is sufficient to declare progression on current treatment but not for entry onto a clinical trial for recurrence
• For patients with WHO grade II glioma progression is defined by any one of the following:
• Development of new lesions or increase of enhancement (radiological evidence of malignant transformation)
• A 25% increase of the T2 or FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy, not attributable to radiation effect or to comorbid events
• For subject with extracranial disease, they must have at least one lesion, not previously irradiated, that can be accurately measured at baseline as >= 10 mm in the longest diameter (except lymph nodes which must have short axis >= 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) or >= 10 mm with calipers by clinical exam OR at least one lesion (measurable and/or non-measurable) that can be accurately assessed by CT/MRI/pain x-ray/clinical exam at baseline and follow up visits
• Subjects must have progressive cancer at the time of study entry; prior experimental (non-FDA approved) therapies (other than drugs that share the same target) and immunotherapies are allowed; patients must not have received these therapies for 30 days or five half-lives of the drug (whichever is less) prior to the initiation of study treatment; toxicities from these therapies should have recovered to =< grade 1, with the exception of stable chronic grade 2 that is not overlapping with presumed toxicities of olaparib
• Female/male of age >= 18 years. This is because no dosing or adverse event data are currently available on the use of olaparib in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >= 50%)
• Hemoglobin >= 10.0 g/dL with no blood transfusion in the past 28 days (within 28 days prior to administration of study treatment)
• Leukocytes >= 3,000/mcL (within 28 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 28 days prior to administration of study treatment)
• Platelet count >= 100 x 10^9/L (within 28 days prior to administration of study treatment)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be =< 5 x ULN (within 28 days prior to administration of study treatment)
• Creatinine clearance estimated using the Cockcroft-Gault equation of >= 51 mL/min (within 28 days prior to administration of study treatment)
• Patients must have a life expectancy >= 16 weeks
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• No previous treatment with the specific assigned study drug or any other PARP inhibitor
• Prior radiation therapy is allowed; patients must not have received radiation therapy within 3 weeks prior to the initiation of study treatment
• Women of child-bearing potential are expected to use highly effective contraception during the study and for 1 month after the last dose of study drug; postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1; postmenopausal is defined as one or more of the following:
• Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
• Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50
• Radiation-induced oophorectomy with last menses > 1 year ago
• Chemotherapy-induced menopause with > 1 year interval since last menses
• Surgical sterilization (bilateral oophorectomy or hysterectomy)
• Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 3 months after last dose of study drug(s) to prevent pregnancy in a partner
• Patients should not enter the study if any of the following exclusion criteria are fulfilled
• Involvement in the planning and/or conduct of the study
• Previous enrollment in the present study
• Participation in another clinical study with an investigational product during the last 30 days or five half-lives of the drug (whichever is less) prior to the initiation of study treatment (6 weeks for nitrosoureas or mitomycin C)
• Any previous treatment with PARP inhibitor, including olaparib
• Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment
• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma, or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for >= 5 years; patients with a history of localized triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
• Resting electrocardiogram (ECG) with corrected QT interval (QTc) > 470 msec or family history of long QT syndrome
• Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil); the required washout period prior to starting olaparib is 2 weeks; because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated drug information reference; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil); the required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents; because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated drug information reference; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
• Persistent toxicities caused by previous cancer therapy; toxicities should have recovered to =< grade 1, excluding alopecia and stable chronic grade 2 toxicity that is not overlapping with presumed toxicities of olaparib
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML
• Patients with symptomatic uncontrolled brain metastases; a scan to confirm the absence of brain metastases is not required; the patient can receive a stable dose of corticosteroids before and during the study if these were started at least 4 weeks prior to treatment; patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days; patients with known uncontrolled brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Major surgery within 2 weeks of starting study treatment; effects from surgeries should have recovered to =< grade 1, with the exception of stable chronic grade 2 that is not overlapping with presumed toxicities of olaparib
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection; examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent and would limit compliance with study requirements
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
• Women who are actively breast feeding
• Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV); HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Olaparib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
• Patients with a known hypersensitivity to olaparib or any of the excipients of the product; history of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib
• Patients with known active hepatitis (i.e. hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids
• Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
• Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable)
• Patients who are receiving any other investigational agents
• Pregnant women are excluded from this study because olaparib is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib, breastfeeding should be discontinued if the mother is treated with olaparib
• Patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), or features suggestive of MDS/AML

• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients with recurrent or refractory solid tumors, including non-Hodgkin lymphomas, histiocytoses (e.g. langerhans cell histiocytosis [LCH], juvenile xanthogranuloma [JXG], histiocytic sarcoma), and central nervous system (CNS) tumors are eligible; patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of cerebrospinal fluid (CSF) or serum tumor markers including alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); in cases where patient enrolls prior to histologic confirmation of recurrent disease, patient is ineligible and should be withdrawn from study if histology fails to confirm recurrence; please note: Patients with Hodgkin lymphoma and plexiform neurofibroma are not eligible
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor Testing Requirement: Tumor sample availability requirement for stage 1 of Pediatric MATCH (patients enrolled from start of study in July 2017 through 12/31/21); Patients must have an formalin-fixed paraffin-embedded (FFPE) tumor sample available for MATCH study testing from a biopsy or surgery that was performed at any point after initial tumor recurrence/progression, or be planned to have a procedure to obtain such a sample that is considered to be of potential benefit by the treating clinicians; a tumor sample from a clinically performed diagnostic (pre-treatment) biopsy will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus
• Please note: Samples that have been decalcified using standardly utilized acid-based decalcification methods are not generally suitable for MATCH study testing; the nucleic acids will have been degraded in the decalcification process
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Tumor molecular profiling report availability requirement for Stage 2 of Pediatric MATCH (patients enrolled starting 2022): In stage 2 of the study, no tumor samples will be submitted for centralized clinical tumor profiling; instead, a tumor molecular profiling report from a College of American Pathologists (CAP)/ Clinical Laboratory Improvements Amendments (CLIA)-approved testing laboratory must be submitted for review by the Molecular Review Committee (MRC)
• This molecular profiling must have been performed on a tumor sample that was obtained at any point after initial tumor recurrence/progression and must be accompanied by a pathology report for the same tumor specimen; a molecular profiling report for a diagnostic (pre-treatment) tumor sample will be acceptable for enrollment onto Pediatric MATCH only for children with high-grade gliomas of the brainstem (diffuse intrinsic pontine gliomas) or thalamus. In the event that molecular profiling reports are available from multiple timepoints, the most recent report should be prioritized for study submission
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); note: neurologic deficits in patients with central nervous system (CNS) tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• ELIGIBILITY CRITERIA FOR ENROLLMENT ONTO APEC1621SC: Patients must have radiographically measurable disease; measurable disease based on imaging obtained less than or equal to 56 days prior to enrollment; patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: NOTE: patient does not need to meet all subprotocol criteria at time of enrollment onto the APEC1621SC screening protocol, but will need to meet all criteria prior to enrollment on any assigned treatment subprotocol. Patients must be enrolled onto a subprotocol within 2 weeks (14 days) of treatment assignment
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age); Note: neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of treatment with subprotocol specified therapy, the patients must have radiographically measurable disease; patients with neuroblastoma who do not have measurable disease but have MIBG+ evaluable are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or CSF
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for RECIST 1.1
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: At the time of enrollment onto a subprotocol, the following general criteria for initiation of therapy will be required:
• Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy and must meet the following minimum duration from prior anticancer directed therapy prior to enrollment to the subprotocol; if after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anticancer agents known to be myelosuppressive: for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anticancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil counts [ANC]): >= 7 days after the last dose of agent; for agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total-body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer (NK) cells, dendritic cells, etc.)
• X-ray therapy (XRT)/External Beam Irradiation including Protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation; note: radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: For patients with solid tumors without known bone marrow involvement:
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions); these patients will not be evaluable for hematologic toxicity
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6
• Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8
• Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1
• Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2
• Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4
• Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Serum glutamate pyruvate transaminase (SGPT) (alanine transferase [ALT]) =< 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Patients must be able to swallow intact capsules/tablets, unless otherwise specified in the subprotocol to which they are assigned
• GENERAL INCLUSION CRITERIA FOR SUBPROTOCOLS: Agent specific limitations on prior therapy will be included with specific treatment subprotocols
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, or because there is currently no available information regarding human fetal or teratogenic toxicities; pregnancy tests must be obtained in females who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Concomitant medications
• Corticosteroids: at the time of consent and enrollment to regimen specific subprotocols, patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment to the subprotocol will not be eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Investigational drugs: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anticancer agents: patients must meet criteria for prior therapy at the time of consent and enrollment to a subprotocol; other investigational agents may not be administered to patients while they are receiving study drug as part of a subprotocol
• Anti-GVHD agents post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have an uncontrolled infection are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Patients who have had a prior solid organ transplant are not eligible
• GENERAL EXCLUSION CRITERIA FOR SUBPROTOCOLS: Additional agent specific criteria will be included with specific treatment subprotocols

• Patients must be enrolled on ANBL00B1 (NCT00904241) or APEC14B1 (NCT02402244) prior to enrollment on ANBL1531 (NCT03126916)
• Patient must be >= 365 days and =< 30 years of age at diagnosis
• Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma (nodular) verified by tumor pathology analysis or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; the following disease groups are eligible:
• Patients with International Neuroblastoma Risk Group (INRG) stage M disease are eligible if found to have either of the following features:
• MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), regardless of additional biologic features; OR
• Age > 547 days regardless of biologic features
• Patients with INRG stage MS disease with MYCN amplification
• Patients with INRG stage L2 disease with MYCN amplification
• Patients > 547 days of age initially diagnosed with INRG stage L1, L2 or MS disease who progressed to stage M without prior chemotherapy may enroll within 4 weeks of progression to stage M
• Patients >= 365 days of age initially diagnosed with MYCN amplified INRG stage L1 disease who progress to stage M without systemic therapy may enroll within 4 weeks of progression to stage M
• Patients initially recognized to have high-risk disease must have had no prior systemic therapy (other than topotecan/cyclophosphamide initiated on an emergent basis and within allowed timing); patients observed or treated with a single cycle of chemotherapy per a low or intermediate risk neuroblastoma regimen (e.g., as per ANBL0531, ANBL1232 or similar) for what initially appeared to be non-high risk disease but subsequently found to meet the criteria will also be eligible; patients who receive localized emergency radiation to sites of life-threatening or function-threatening disease prior to or immediately after establishment of the definitive diagnosis will be eligible
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/sex as follows:
• 1 to < 2 years: male = 0.6; female = 0.6
• 2 to < 6 years: male = 0.8; female = 0.8
• 6 to < 10 years: male = 1; female = 1
• 10 to < 13 years: male = 1.2; female = 1.2
• 13 to < 16 years: male = 1.5; female = 1.4
• >= 16 years: male = 1.7; female = 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, and
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 10 x ULN; for the purposes of this study, ULN for SGPT (ALT) is 45
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of > 50% by echocardiogram or radionuclide angiogram
• No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
• Patients with INRG stage L2 tumors without amplification of MYCN regardless of tumor histology (may meet criteria for high risk classification but are not eligible for this trial)
• Patients with bone marrow failure syndromes
• Patients for whom targeted radiopharmaceutical therapy would be contraindicated due to underlying medical disorders
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

• There is no age limit for the low risk stratum (stage I ovarian immature teratoma and stage I non-seminoma or seminoma malignant GCT [all sites])
• Standard risk 1: Patient must be < 11 years of age at enrollment
• Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
• Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I germ cell tumor; for the standard risk arms, patients must be newly diagnosed with metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary extracranial germ cell tumor in any of the categories outlined below is required of all patients at enrollment except for those who were initially diagnosed with stage I non-seminoma malignant GCT and later recur during observation post surgery off study; for these patients, if elevated tumor markers rise to > 5 x upper limit of normal (ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is not required for enrollment
• Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB; grade: 2 or 3; histology: pure immature teratoma (may contain microscopic foci of yolk sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT); tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; all ages
• Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage: COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA, IB and IS; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
• Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular stage IA IB, and IS; histology: must contain at least one of the following: may contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
• Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus Classification [IGCCC] criteria DO NOT apply); histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) < 11
• Standard risk 2 (SR2)
• Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) >= 11 and < 25
• Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; tumor markers: must be IGCCC good risk; post op: alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) < 3.0 x normal; age (years) >= 11 and < 25
• Site: extragonadal; stage: COG stage II; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) >= 11 and < 25
• Notes:
• IGCCC criteria only apply to SR2 patients with a testicular primary tumor
• Use post-op tumor marker levels to determine IGCCC risk group
• Stage 1 seminoma patients are not eligible for the standard risk arms of the study
• For the low risk stage I non-seminoma MGCT and the standard risk arms, components of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the only malignant component present, then it must be deemed by the pathologist to be greater than a "microscopic component" of yolk sac tumor
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
• Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients)
• Adequate renal function defined as:
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment): (mg/dL)
• 1 month to < 6 months male: 0.4 female: 0.4
• 6 months to < 1 year male: 0.5 female: 0.5
• 1 to < 2 years male: 0.6 female: 0.6
• 2 to < 6 years male: 0.8 female: 0.8
• 6 to < 10 years male: 1 female: 1
• 10 to < 13 years male: 1.2 female: 1.2
• 13 to < 16 years: male: 1.5 female: 1.4
• >= 16 years male: 1.7 female: 1.4
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT is 45 U/L) (within 7 days prior to enrollment)
• Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3 (within 7 days prior to enrollment) AND
• Platelet count >= 100,000/mm^3 (within 7 days prior to enrollment)
• Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
• Eligibility criteria to participate in the pilot study of the AYA-Hears instrument (patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be enrolled on the AGCT1531 SR2 arm in order to participate
• >= 11 and < 25 years old at enrollment
• Able to fluently speak and read English
• Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy including diagnoses other than germ cell tumor
• Followed for cancer or survivorship care at one of the following institutions:
• Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
• Dana Farber/Harvard Cancer Center
• Hospital for Sick Children
• Children's Hospital of Eastern Ontario
• Oregon Health and Science University
• Seattle Children's Hospital
• Yale University
• Patients with any diagnoses not listed including:
• Stage I testicular cancer patients who have undergone primary RPLND (retroperitoneal lymph node dissection)
• Pure dysgerminoma
• Pure mature teratoma
• Pure immature teratoma COG stage I, grade I
• Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) >= 1000 ng/mL
• Pure immature teratoma COG stage II
•IV or FIGO stage IC to IV
• "Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage III or IV EG, or IGCCC intermediate or poor risk testicular), or
• Primary central nervous system (CNS) germ cell tumor
• Germ cell tumor with somatic malignant transformation
• Spermatocytic seminoma
• Patients must have had no prior systemic therapy for the current cancer diagnosis
• Patients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain [stage IV disease] would be considered poor risk and therefore not eligible for this trial)
• Patients with significant, pre-existing co-morbid respiratory disease that contraindicate the use of bleomycin are ineligible for the standard risk arms of the trial
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
• Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])

• Enrollment must occur within 6 months of initial disease presentation OR within 6 months of refractory disease, disease progression, disease recurrence, second or secondary malignancy, or post-mortem
• Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome, Registry and Future Contact components of APEC14B1 any time after they reach age of majority
• Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent or young adult populations are eligible for enrollment as follows:
• All cancer cases with an International Classification of Diseases for Oncology (ICD-O) histologic behavior code of two "2" (carcinoma in situ) or three "3" (malignant)
• All neoplastic lesions of the central nervous system regardless of behavior, i.e., benign, borderline or malignant
• The following other benign/borderline conditions:
• Mesoblastic nephroma
• Teratomas (mature and immature types)
• Myeloproliferative diseases including transient myeloproliferative disease
• Langerhans cell histiocytosis
• Lymphoproliferative diseases
• Desmoid tumors
• Gonadal stromal cell tumors
• Subjects must be =< 25 years of age at time of original diagnosis, except for patients who are being screened specifically for eligibility onto a COG (or COG participating National Clinical Trials Network [NCTN]) therapeutic study, for which there is a higher upper age limit
• All patients or their parents or legally authorized representatives must sign a written informed consent and agree to participate in at least one component of the study; parents will be asked to sign a separate consent for their own biospecimen submission
• If patients or their parents or legally authorized representatives have not signed the Part A subject consent form at the time of a diagnostic bone marrow procedure, it is recommended that they initially provide consent for drawing extra bone marrow using the Consent for Collection of Additional Bone Marrow; consent using the Part A subject consent form must be provided prior to any other procedures for eligibility screening or banking under APEC14B1

• ELIGIBILITY CRITERIA
•CASES
• Diagnosis of primary cancer at age 21 or younger, irrespective of current age
• No prior history of allogeneic (non-autologous) hematopoietic cell transplant
• Development of one of the following key adverse events at any time following initiation of cancer therapy:
• Cardiac dysfunction; please note: case enrollment has been closed due to achievement of target accrual
• Ischemic stroke (IS)
• Subsequent malignant neoplasm (SMN)
• Avascular necrosis (AVN); please note: case enrollment has been closed due to achievement of target accrual
• Submission of a blood specimen (or in certain cases a saliva specimen) to the Coordinating Center at the University of Alabama at Birmingham as per the requirements; please note: if a patient is currently receiving active cancer treatment, it is preferable to obtain the blood sample at a time when the patient's white blood cell (WBC) is > 2,000
• Written informed consent from the patient and/or the patient's legally authorized guardian
• In active follow up by a COG institution; active follow up will be defined as date of last visit or contact by a COG institution within the past 24 months; any type of contact, including contact specifically for participation in ALTE03N1, qualifies as active follow-up; please note: treatment on a COG (or legacy group) therapeutic protocol for the primary cancer is NOT required
• ELIGIBILITY CRITERIA
•CONTROLS
• CONTROL: Diagnosis of primary cancer at age 21 or younger, irrespective of current age
• CONTROLS: No prior history of allogeneic (non-autologous) hematopoietic cell transplant
• CONTROLS: No clinical evidence of any of the following key adverse events:
• Cardiac dysfunction (CD); please note: if a patient is currently receiving active cancer treatment, it is preferable to obtain the blood sample at a time when the patient's WBC is > 2,000
• Ischemic stroke (IS)
• Avascular necrosis (AVN)
• Subsequent malignant neoplasm (SMN)
• CONTROLS: Submission of a blood specimen (or in certain cases a saliva specimen) to the Coordinating Center Laboratory at the University of Alabama at Birmingham as per the requirements
• CONTROLS: Written informed consent from the patient and/or the patient's legally authorized guardian
• CONTROLS: In active follow up by a COG institution; active follow up will be defined as date of last visit or contact by a COG institution within the past 24 months; any type of contact, including contact specifically for participation in ALTE03N1, qualifies as active follow-up; please note: treatment on a COG (or legacy group) therapeutic protocol for the primary cancer is NOT required

• Subjects must be able to understand the nature of this trial and provide written informed consent, prior to any study specific procedures. Patients with impaired decision making capacity (IDMC) who have a close caregiver or legally authorized representative (LAR) may be considered eligible for this study at the treating physician's discretion, provided that the physician is reasonably sure that the possible risks and benefits of the study are clear and that the patient will take the drug as prescribed
• Subjects must be diagnosed with a solid malignant tumor (other than cholangiocarcinoma primary central nervous system [CNS]) that has progressed despite standard therapy, or for which no effective standard therapy exists. Patients with cholangiocarcinoma are no longer allowed as this cohort has closed to accrual. Patients with CNS tumors, e.g. glioma, are not allowed
• Patients must have biopsy-confirmed evidence of an IDH1 or IDH2 mutation, confirmed in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory, associated with neomorphic activity of the encoded proteins
• Patients must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies. Tumor biopsies will be performed on the most accessible biopsiable site of disease. All possible precautions to avoid complications will be taken, including discussions in multidisciplinary meetings, if needed. If a patient opts out of a pre-treatment biopsy, biopsy is not possible, or if a pre-treatment biopsy does not yield sufficient tissue for analysis, the patient must be willing to provide an sufficient archival formalin-fixed paraffin-embedded (FFPE) specimen for liquid chromatography/mass spectrometry (LC/MS) analysis of 2HG in order to enroll on the study. Permission of the study principal investigator (PI) is required in all of the above scenarios
• In order to maximize the availability of newly obtained specimens for 2-HG analysis, at least 10 biopsies will be required in each group (cholangiocarcinoma and other solid tumors) of 14 patients treated in the first stage of this Simon two-stage design. Thus if 4 patients in an arm have already opted out, further patients may only enroll on that arm (in the first stage) if they agree to undergo the pre- and on-treatment biopsies. If a patient has agreed to undergo the two biopsies and undergoes the pre-treatment biopsy, he or she may not opt out of the second biopsy unless such a biopsy would not be safe (e.g. inaccessible tumor). Permission of the study PI is required in this scenario
• All patients must be willing to provide 5 unstained archival slides, if available, for pre-treatment 2-HG analysis and correlation with 2-HG levels in pre-treatment frozen specimens
• Patients must be willing to undergo extra blood sampling for correlative studies
• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Patients must have at least one lesion, not previously irradiated, that can be accurately measured at baseline as >= 10 mm in the longest diameter (except lymph nodes which must have short axis >= 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) or >= 10 mm with callipers by clinical exam OR at least one lesion (measurable) that can be accurately assessed by CT/MRI/clinical exam at baseline and follow up visits
• Subjects must have progressive cancer at the time of study entry
• Prior experimental (non-Food and Drug Administration [FDA] approved) therapies (other than drugs that target ATR) and immunotherapies are allowed. Patients must not have received these therapies for 30 days or five half-lives of the drug (whichever is less) prior to the initiation of study treatment
• Toxicities from prior therapies should have recovered to =< grade 1, with the exception of stable chronic grade 2 toxicities that are not overlapping with presumed toxicities of olaparib
• Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (MRI or CT scan) during the screening period
• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial
• If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated. If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load
• Female/male of age >= 18 years. This is because no dosing or adverse event data are currently available on the use of olaparib or AZD6738 in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
• Eastern Cooperative Oncology Group (ECOG) 0-1 (Karnofsky >= 70%)
• Hemoglobin >= 10.0 g/dL with no blood transfusion in < 14 days prior to starting therapy (measured within 14 days prior to administration of study treatment)
• Leukocytes >= 3,000/mcL (measured within 14 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (measured within 14 days prior to administration of study treatment)
• Platelet count >= 100 x 10^9/L (measured within 14 days prior to administration of study treatment)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (measured within 14 days prior to administration of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be =< 5 x ULN (measured within 14 days prior to administration of study treatment)
• Creatinine clearance estimated using the Cockcroft-Gault equation of >= 51 mL/min or based on a 24 hour urine test (measured within 14 days prior to administration of study treatment)
• No features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) on peripheral blood smear when performed as clinically indicated
• Patients must have a life expectancy of >= 16 weeks, in the opinion of the treating physician
• Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
• Prior radiation therapy is allowed. Patients must not have received radiation therapy within 3 weeks prior to the initiation of study treatment
• Women of child-bearing potential are expected to use highly effective contraception during the study and for 6 months after the last dose of study drug. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1
• Postmenopausal is defined as:
• Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
• Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the post-menopausal range for women under 50
• Radiation-induced oophorectomy with last menses > 1 year ago
• Chemotherapy-induced menopause with > 1 year interval since last menses
• Surgical sterilization (bilateral oophorectomy or hysterectomy)
• Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 6 months after last dose of study drug(s) to prevent pregnancy in a partner
• Patients with human immunodeficiency virus (HIV) on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial
• Involvement in the planning and/or conduct of the study
• Previous enrollment in the present study
• Participation in another clinical study with an investigational product during the last 30 days or five half-lives of the drug (whichever is less) prior to the initiation of study treatment
• Any previous treatment with a PARP inhibitor
• Any previous treatment with AZD6738 or any other ATR inhibitor
• Patients receiving any systemic chemotherapy or radiotherapy within 3 weeks prior to study treatment
• Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma, or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for >= 5 years. Patients with a history of localized triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
• Resting electrocardiography (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, Fridericia's corrected QT [QTcF] prolongation > 500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome
• Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks
• Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
• Persistent toxicities caused by previous cancer therapy. Toxicities should have recovered to =< grade 1, excluding alopecia, or should be stable chronic grade 2 toxicities that do not overlap with presumed toxicities of olaparib and/or AZD6738
• Patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) or features suggestive of MDS/AML
• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are not eligible if the treating physician determines that immediate CNS specific treatment is required, and a risk-benefit analysis (discussion) by the patient and the investigator does not favor participation in the clinical trial. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study if these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• Major surgery within 2 weeks of starting study treatment. Major surgeries typically require general anesthesia, are associated with an estimated blood loss of > 500 mL, and require an overnight hospital stay. Examples include laparoscopic surgery, open resection of organs, joint replacements and other orthopedic surgeries, and vascular or intracranial surgeries. Examples of minor surgeries include those performed on an ambulatory basis, cataract surgery, dental surgeries, cutaneous, endoscopic, and arthroscopic procedures. Effects from major surgeries should have recovered to =< grade 1, with the exception of stable chronic grade 2 toxicities that are not overlapping with presumed toxicities of olaparib and/or AZD6738
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent and would limit compliance with study requirements
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
• Women who are actively breast feeding
• Patients with a known hypersensitivity to olaparib or AZD6738 or any of the excipients of the products. History of allergic reactions attributed to compounds of similar chemical or biologic composition to olaparib or AZD6738
• Previous allogeneic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
• Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable within the last 28 days)
• Patients who are receiving any other investigational agents
• Pregnant women are excluded from this study because olaparib is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib, breastfeeding should be discontinued if the mother is treated with olaparib
• Receiving, or having received during the 14 days prior to first dose, corticosteroids (at a dose > 10 mg prednisone/day or equivalent) for any reason
• Any of the following cardiac diseases currently or within the last 6 months (by New York Heart Association (NYHA) >= class 2 where applicable):
• Unstable angina pectoris
• Congestive heart failure or known reduced left ventricular ejection fraction (LVEF) < 55%
• Acute myocardial infarction
• Conduction abnormality not controlled with pacemaker or medication e.g. complete left bundle branch block, third degree heart block
• Significant ventricular or supraventricular arrhythmias e.g. (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
• Patients at risk of brain perfusion problems, e.g., medical history of carotid stenosis or pre-syncopal or syncopal episodes, history of transient ischemic attacks (TIAs)
• Uncontrolled hypertension (grade 2 or above) requiring clinical intervention
• Any factors that increase the risk of corrected QT (QTc) prolongation or risk of arrhythmic events such as congestive heart failure, unstable angina pectoris, acute myocardial infarction, hypokalemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age, conduction abnormality not controlled with pacemaker or medication
• Patients with relative hypotension (< 90/60 mm Hg) or clinically relevant orthostatic hypotension, including a fall in blood pressure of > 20 mm Hg
• Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection, with clinically significant sequelae that would preclude adequate absorption of AZD6738

• Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621K based on the presence of an actionable mutation as defined in APEC1621SC
• Patients must be >= than 12 months and =< 21 years of age at the time of study enrollment
• Patients must have a body surface area >= 0.78 m^2 at enrollment
• Patients must be able to swallow intact tablets
• Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG)+ evaluable disease are eligible. Measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular Therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam Irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to AG-120 (ivosidenib) or other IDH1 inhibitors
• For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment)
• For patients with solid tumors without known bone marrow involvement: Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood count (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment), or
• A serum creatinine based on age/gender (within 7 days prior to enrollment)
• Age 1 to < 2 years, maximum serum creatinine (mg/dL) male 0.6, female 0.6
• Age 2 to < 6 years, maximum serum creatinine (mg/dL) male 0.8, female 0.8
• Age 6 to < 10 years, maximum serum creatinine (mg/dL) male 1, female 1
• Age 10 to < 13 years, maximum serum creatinine (mg/dL) male 1.2, female 1.2
• Age 13 to < 16 years, maximum serum creatinine (mg/dL) male 1.5, female 1.4
• Age >= 16 years, maximum serum creatinine (mg/dL) male 1.7, female 1.4
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamate-pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. (For the purpose of this study, the ULN for SGPT is 45 U/L) (within 7 days prior to enrollment)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Corrected QT (QTc )interval =< 450 milliseconds (within 7 days prior to enrollment)
• Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause Torsades de Pointes. Patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are available
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
• All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
• Pregnant or breast-feeding women will not be entered on this study due to risks because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective non-hormonal contraceptive method for the duration of study treatment and for at least 1 month after last dose of AG-120 (ivosidenib). Since AG-120 (ivosidenib) may decrease concentrations of hormonal contraceptives, hormonal contraceptives are not considered effective contraception when co-administered with AG-120 (ivosidenib)
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are currently receiving drugs that are strong inducers or moderate to strong inhibitors of CYP3A4 are not eligible. Strong inducers or moderate to strong inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed. In addition, patients receiving sensitive or narrow therapeutic range substrates of CYP3A4 are not eligible
• Patients with a history of progressive multifocal leukoencephalopathy are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

• Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621M based on the presence of an actionable mutation as defined in APEC1621SC
• Patients must be >=12 months and =< 21 years of age at the time of study enrollment
• Patients must have a body surface area >= 0.29 m^2 at enrollment
• Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible. Measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebral spinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50 for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive.
• >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent.
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radio-pharmaceutical therapy
• Patients must not have received prior exposure to tipifarnib
• For patients with solid tumors without known bone marrow involvement (within 7 days prior to enrollment):
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• For patients with solid tumors without known bone marrow involvement (within 7 days prior to enrollment):
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment) or
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age: Maximum serum creatinine (mg/dL)
• 1 to < 2 years: male (0.6), female (0.6)
• 2 to < 6 years: male (0.8), female (0.8)
• 6 to < 10 years: male (1), female (1)
• 10 to < 13 years: male (1.2), female (1.2)
• 13 to < 16 years: male (1.5), female (1.4)
• >= 16 years: male (1.7), female (1.4)
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. (For the purpose of this study, the ULN for SGPT is 45 U/L.) (within 7 days prior to enrollment)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
• Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0) resulting from prior therapy must be =< grade 2
• Patients must be able to swallow intact tablets or crushed tablets mixed in water, orange juice, apple juice, tomato juice, ginger ale, applesauce, yogurt, protein shake, or a dietary supplement drink (such as Ensure). Percutaneous endoscopic gastrostomy (PEG)-tube or nasogastric tube administration is permitted
• All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective contraceptive methods for the duration of study treatment. Both female subjects and male subjects with female partners of child-bearing potential must agree to use a highly effective method of contraception for 2 weeks prior to protocol therapy, during, and at least 4 weeks after last dose of tipifarnib. In addition, since tipifarnib could induce toxicity of male reproductive organs and cause impairment of fertility, sperm cryopreservation should be recommended for male subjects wishing to preserve their fertility following tipifarnib treatment
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4/5 or UGT are not eligible. Strong inducers or inhibitors of CYP3A4/5 or UGT should be avoided from 14 days prior to the 1st dose of tipifarnib to the end of the study. In addition, patients receiving agents that are sensitive or narrow therapeutic range substrates of CYP3A4/5 are not eligible. Note: CYP3A4/5 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
• Patients with known hypersensitivity to tipifarnib or any components of the tablet are not eligible
• Patients with hypersensitivity to imidazoles, such as clotrimazole, ketoconazole, miconazole and others in this drug class are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

1. Participant is able and willing to provide informed consent (≥18 years), or informed consent is obtained by the parent or legal guardian for minor participants, with the minor providing age appropriate assent, according to local law and regulations; 2. Life expectancy ≥ 12 weeks; 3. Known high-risk neuroblastoma OR previously intermediate-risk neuroblastoma that has relapsed or progressed to high-risk, with failure to achieve complete response with standard therapy (defined as at least 4 cycles of aggressive multi-drug induction chemotherapy with or without radiation and surgery, or according to a standard high-risk treatment/neuroblastoma protocol), OR who are medically ineligible to receive standard treatment OR who are intolerant to standard treatment; 4. Adequate recovery from acute toxic effects of any prior therapy, as deemed by the Investigator or treating Sub-Investigator; 5. Adequate liver function as defined by the following laboratory values obtained within 28 days prior to administration of 64Cu-SARTATE: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN); 6. Adequate renal function; 7. Adequate laboratory parameters: Absolute neutrophil count > 1.0 x 10 9/L; Platelet count > 50 x 10 9/L; Total bilirubin <1.5 x ULN; 8. Karnofsky or Lansky performance status ≥50; 9. All participants must have a hematopoietic stem cell product available (minimum CD34+ cell dose is ≥2 x 10 6 cells/kg); 10. Sexually active participants of reproductive potential must practice an effective method of birth control while participating on this study, to avoid possible damage to the fetus. Abstinence is considered acceptable; 11. 64Cu-SARTATE uptake on the 4 hour scan (SUVmax) of any lesion equal to or higher than that of the liver in order to move on to the therapy phase of the study. 1. Participants with disease of any major organ system that would compromise their ability to tolerate therapy, as deemed by the Investigator or treating Sub-Investigator; 2. Any other active malignancy, or a history of prior malignancy within the past 3 years; 3. History of cardiac failure as evidenced by: dyspnea at rest, exercise intolerance, oxygen requirement, clinically significant cardiac dysfunction; 4. Planned administration of chemotherapy, anti-cancer cytokine therapy, immunotherapy or radiotherapy within 2 weeks prior to the administration of 64Cu-SARTATE; 5. Administration of therapeutic dose of 131I-MIBG within 8 weeks prior to the administration of 64Cu-SARTATE; 6. External beam radiation therapy (EBRT) to both kidneys or a single functioning kidney within 12 months prior to the administration of 64Cu-SARTATE; 7. Administration of any investigational agents within 21 days prior to administration of 64Cu-SARTATE; 8. Treatment with long acting somatostatin analogues (administered within 28 days prior to the administration of 64Cu-SARTATE), or short acting somatostatin analogues (administered within 24 hours prior to the administration of 64Cu-SARTATE); 9. Known sensitivity or allergy to somatostatin analogues; 10. Previous peptide receptor radionuclide therapy (PRRT); 11. Female participants who are pregnant or lactating; 12. Participants who are on hemodialysis; 13. QTc interval ≥ 0.45 seconds as measured by Screening ECG; 14. Participants with uncontrolled infection(s); 15. Any medical condition which the Investigator feels may interfere with the procedures or evaluations of the study; 16. Participants 12 months and younger will be excluded from cohorts where the planned single or cumulative administered activity is modelled to deliver a radiation dose to the marrow that exceeds 2 Gy.

• Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621N based on the presence of an actionable mutation
• Patients must be >= 12 months and =< 21 years of age at the time of study enrollment
• Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible. Measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard MRI or CT
• Note: The following do not qualify as measurable disease:
• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
• Elevated tumor markers in plasma or cerebral spinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
• Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive.
• >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
• Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil [ANC] counts): >= 7 days after the last dose of agent.
• Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
• Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator
• Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
• Stem cell infusions (with or without total body irradiation [TBI]):
• Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
• Autologous stem cell infusion including boost infusion: >= 42 days
• Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
• Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
• Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
• Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
• Patients must not have received prior exposure to selpercatinib (LOXO-292) or other specific RET inhibitors
• For patients with solid tumors without known bone marrow involvement (within 7 days prior to enrollment):
• Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
• For patients with solid tumors without known bone marrow involvement (within 7 days prior to enrollment):
• Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment) or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age: Maximum serum creatinine (mg/dL)
• 1 to < 2 years: male (0.6), female (0.6)
• 2 to < 6 years: male (0.8), female (0.8)
• 6 to < 10 years: male (1), female (1)
• 10 to < 13 years: male (1.2), female (1.2)
• 13 to < 16 years: male (1.5), female (1.4)
• >= 16 years: male (1.7), female (1.4)
• Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. (within 7 days prior to enrollment) (For the purpose of this study, the ULN for SGPT is 45 U/L.)
• Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
• Corrected QT (QTc) interval =< 480 milliseconds (within 7 days prior to enrollment)
• All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
• Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two (2) highly effective contraceptive method for the duration of study treatment and for at least 2 weeks after the last dose of selpercatinib (LOXO-292). Male study participants are to refrain from sperm donation during treatment and for 2 weeks after the last dose of selpercatinib (LOXO-292)
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anti-cancer agents are not eligible
• Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
• Patients who are currently receiving drugs that are moderate or strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
• Proton pump inhibitors (PPIs), H2 receptor antagonists and antacids: Concomitant use of PPIs during selpercatinib (LOXO-292) therapy should be avoided if feasible. If co-administration of selpercatinib and PPI is necessary, administer selpercatinib with a meal. If H2 receptor antagonist is necessary, administer selpercatinib 2 hours before or 10 hours after H2 receptor antagonist administration. If antacid use is necessary, administer selpercatinib 2 or more hours before or 2 or more hours after antacid administration
• Patients who have major surgery within 14 days prior to cycle 1 day 1 (C1D1) are not eligible. (Central line placement or subcutaneous port placement is not considered major surgery)
• Patients with known clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of selpercatinib (LOXO-292) are excluded
• Patients with known hypersensitivity to any of the components of the investigational agent, LOXO 292 are excluded
• Patients with uncontrolled hypertension are excluded
• Patients with uncontrolled symptomatic hyperthyroidism and hypothyroidism (i.e. the patient required a modification to current thyroid medication in 7 days prior to enrollment) are excluded
• Patients with uncontrolled symptomatic hypercalcemia and hypocalcemia are excluded
• Patients who have an uncontrolled infection are not eligible
• Patients who have received a prior solid organ transplantation are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

• At study entry patients must be > 1 year
• Relapsed or refractory high risk neuroblastoma (as defined by International Neuroblastoma Risk Group (INRG) criteria)
• MIBG avid disease on imaging within 4 weeks to study entry.
• ≥ 3 months since any myeloablative chemotherapy / stem cell rescue
• ≥ 42 days since any other immunotherapy e.g. tumour vaccines. At least 3 half lives since last dose of any monoclonal antibody therapy.
• Patients must have a performance status greater or equal 60% (Lansky Score or Karnofsky)
• Estimated life expectancy ≥ 12 weeks
• Adequate bone marrow function: Absolute Neutrophil Count (ANC) >1.0 x 10/L, platelets, 20 x 10/L and haemoglobin > 8.0 g/dL.
• Adequate renal function: serum creatinine <1.5 mg/dL or a estimated creatinine clearance or radioisotope Glomerular Filtration Rate Study (GFR) of > 60 mL/minute/1.73m2.
• Adequate cardiac function: shortening fraction of 28 % by echocardiogram.
• Adequate hepatic function: Alanine transaminase (ALT) or Aspartate transaminase (AST) < 5 x ULN and a total bilirubin < 1.5 x Upper Limit of Normal (ULN)
• Adequate lung function: Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) >60% of the predicted by pulmonary function tests. Children unable to do Pulmonary Function Tests (PFTs) should have no dyspnea at rest and a pulse oximetry >94% on room air.
• Adequate pancreatic function: serum lipase < 1.5 x upper limit normal
• Patients may have had prior Central Nervous System (CNS) metastasis at point of entry to study, but patients with mIBG avid parenchymal brain lesions will be excluded. All CNS disease must be treated and stable prior for at least 4 weeks prior to starting trial 131-I mIBG therapy (see section 4). Patients with extra-axial disease (e.g. skull (bone) metastasis that do not invade the dura) may be enrolled providing there is no evidence of brain oedema.
• Patients must consent to the placement of a central venous line, if one has not already been placed.
• Patients must have no immediate requirements for palliative chemotherapy, radiotherapy or surgery.
• Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
• Patients with seizure disorders may be enrolled if seizures are well controlled.
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional and national requirements for clinical trials must be met.
• Expression of PD-L1 by tumour is not a pre-requisite
• Parents or carers willing and able to comply with radiation safety measures needed for 131-I mIBG administration.
• Patient must be judged capable of tolerating isolation procedures associated with 131-I-mIBG therapy Exclusion Criteria
• Patients who have previously received ch14.18 (CHO or SP2/0) will not be excluded unless they have had severe or life threatening toxicity necessitating withdrawal of treatment previously or if they have a strong/neutralizing Human Antichimeric Antibody (HACA) (≥ 10 μg/ml)
• Patients who have had previous 131-I mIBG therapy will not be excluded
• Patients previously treated with Nivolumab or any other PD-1 or PD-L1 targeting antibodies will be excluded from the study
• Previous allogeneic stem cell transplant or solid organ transplant
• Patients should be excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
• Patients receiving systemic corticosteroids (other than physiological replacement) or other immunosuppressive agents within 14 days prior to study entry
• Unable to maintain platelets ≥ 50 x 109/l without transfusion
• HIV or Hepatitis B or C infection
• Patients with significant intercurrent illnesses and/or any of the following:
• Patients with symptoms of congestive heart failure or uncontrolled cardiac rhythm disturbance.
• Patients with significant psychiatric disabilities or uncontrolled seizure disorders.
• Patients with active infections.
• Patients with a clinically significant neurologic deficit or objective peripheral neuropathy (Grade >2) are ineligible.
• Patients with clinically significant, symptomatic, pleural effusions.
• Patients who require, or are likely to require, corticosteroid or other immunosuppressive drugs.

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Male or female participants ≥ 18 years of age (or age ≥ regionally approved age of consent for participation in investigational clinical studies) at the time of signing the informed consent.
• Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
• Adequate organ and marrow function
• History of trauma or major surgery within 28 days prior to the first dose of study treatment.
• Prior treatment with an anti-TIGIT antibody.
• Any active or prior autoimmune disease that required treatment within 3 years of the first dose of study treatment.
• Prior chemotherapy, targeted small-molecule therapy, immunotherapy, or biologic agents, or use of other investigational drugs within 28 days before first dose of study treatment.
• Discontinued prior immunotherapy for immune related adverse events with a high severity. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Inclusion Criteria
• Histologically or cytologically confirmed diagnosis of locally-advanced unresectable or metastatic solid tumor, including primary brain tumors
• Participants with non-squamous NSCLC must have progressed during or after standard treatment or for which no standard treatment is available
• Participants with other disease types must have progressed during or after ≥1 prior line of systemic therapy for locally-advanced unresectable or metastatic disease
• Disease progression during or after, or intolerance of, the most recent line of systemic therapy
• Disease demonstrating HER2 alterations (overexpression/amplification or HER2 activating mutations), as determined by local or central testing processed in a Clinical Laboratory Improvement Amendments (CLIA)- or International Organization for Standardization (ISO) accredited laboratory, according to one of the following:
• HER2 overexpression/amplification from fresh or archival tumor tissue or blood
• Known activating HER2 mutations detected in fresh or archival tumor tissue or blood
• Have measurable disease per RECIST v1.1 criteria according to investigator assessment
• Have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Exclusion Criteria
• Participants with breast cancer, gastric or gastroesophageal junction adenocarcinoma, or CRC whose disease shows HER2 amplification/overexpression.
• Previous treatment with HER2-directed therapy; participants with uterine serous carcinoma or HER2-mutated gastric or gastroesophageal junction adenocarcinoma without HER2-overexpression/amplification may have received prior trastuzumab
• Known hypersensitivity to any component of the drug formulation of tucatinib or trastuzumab (drug substance, excipients, murine proteins), or any component of the drug formulation of fulvestrant in participants with HR+ HER2-mutated breast cancer
• History of exposure to a 360 mg/m² doxorubicin-equivalent or >720 mg/m^2 epirubicin-equivalent cumulative dose of anthracyclines
• Treatment with any systemic anti-cancer therapy, radiation therapy, major surgery, or experimental agent within ≤3 weeks of first dose of study treatment or are currently participating in another interventional clinical trial. There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

• First diagnosis of malignant neoplasm (International Classification of Diseases for Oncology [ICD-O] behavior code of "3") in first and continuous remission at the time of enrollment
• Curative cancer treatment must have included chemotherapy (including cellular therapy) and/or radiation (including radioactive iodine)
• Note: Childrens Oncology Group (COG) therapeutic trial participation is not required
• All cancer treatment must have been completed within 3-36 calendar months prior to enrollment
• Patients must have a life expectancy of > 1 year
• Self-report of < 420 minutes of moderate-to-vigorous physical activity per week as assessed via the study-specific Physical Activity Worksheet
• Note: See COG Study Web Page for the Godin-Shephard Leisure Time Physical Activity Questionnaire or link to online calculator
• Ambulatory and no known medical contraindications to increasing physical activity
• Note: Patients with amputation, rotationplasty, or other prothesis are not automatically excluded as long as they are ambulatory and have no known medical contraindications to increasing physical activity and all other eligibility criteria are satisfied
• No known significant physical or cognitive impairment that would prevent use of the electronic devices used for the protocol intervention (e.g. Fitbit, smartphone, tablet, or computer)
• Able to read and write English
• Note: For patients < 18 years, consenting parent/legal guardian does not have to be able to read and write English
• All patients and/or their parents or legal guardians must sign a written informed consent
• Note: Informed consent may be obtained electronically/online if allowed by local site policy and Institutional Review Board (IRB)/Research Ethics Board (REB) of record
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Post-menarchal female patients who are pregnant or planning to become pregnant in the next year are excluded
• Note: Pregnancy status can be established by clinical history with patient. Post-menarchal female patients are eligible as long as they agree to use an effective contraceptive method (including abstinence) during study participation
• Patients with previous hematopoietic stem cell transplant (HSCT) are excluded
• Note: Patients with previous autologous HSCT, chimeric antigen receptor T-cell (CAR T-cell) therapy, and other cellular cancer therapies can participate as long as all other eligibility criteria are satisfied

• Subjects with advanced or metastatic solid tumor in subjects whose disease has progressed despite standard therapy, or who has no further standard therapy, or who is unsuitable for available standard treatment options.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with adequate organ function For dose expansion study only:
• Advanced or metastatic gastric cancer, gastroesophageal junction carcinoma, esophageal adenocarcinoma, and pancreatic ductal adenocarcinoma without further standard therapy or unsuitable for available standard treatment options.
• Must have CLDN18.2-positive tumor expression as determined by the CLDN18.2 IHC assay Exclusion Criteria
• Prior exposure to CLDN18.2 -targeted therapy
• Prior exposure to 4-1BB agonists
• Known active or chronic Hepatitis B or Hepatitis C, other hepatitides
• Unstable/active ulcer or digestive tract bleeding within 6 weeks
• Active autoimmune disease requiring systemic treatment within the past 2 years
• Active interstitial lung disease (ILD) or pneumonitis or a history of ILD or pneumonitis requiring treatment
• Known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment;
• New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, severe/unstable angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack (TIA), arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), deep vein thrombosis, or coronary artery bypass grafting (CABG) in the previous 6 months
• Diagnosis of immunodeficiency such as known active HIV

• STEP 0 (PRE-REGISTRATION) INCLUSION CRITERIA
• Patient must be >= 18 years of age on day of consent
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Patient must have a diagnosis of pancreatic cancer and have successfully undergone a curative intent surgical resection and must have no evidence of recurrent disease as determined by the investigator
• NOTE: This includes patients with adenocarcinoma, acinar carcinoma, squamous cell carcinoma adenosquamous and variants thereof. Patients with neuroendocrine tumors are excluded from enrolling
• Patient must (1) be planning to receive, (2) be receiving or (3) have received at least three combined months (i.e., 12 weeks) of perioperative (neoadjuvant, adjuvant or a combination of both) systemic, multi-agent chemotherapy. Patients may have had up to 6 months of perioperative systemic therapy as deemed appropriate by their primary treating medical team (patients can have received radiation or chemoradiation in addition to this 6 month course)
• Patient must be no more than 12 weeks from their most recent treatment (this may be chemotherapy, radiotherapy or surgery)
• Patient must have a known pathogenic or likely pathogenic germline or somatic mutation in BRCA1, BRCA2, or PALB2, as determined by a Clinical Laboratory Improvement Amendments (CLIA) certified or equivalently-accredited laboratory. Mutations must be considered pathogenic or likely pathogenic by a reference database such as ClinVar or OncoKb.org
• STEP 1 (RANDOMIZATION) INCLUSION CRITERIA
• Patient must have met the eligibility criteria outlined above
• Patient must have undergone at least 3 combined months (i.e., 12 weeks) of perioperative (neoadjuvant, adjuvant or a combination of both) systemic, multi-agent chemotherapy. Patients may have had up to 6 months of perioperative systemic therapy as deemed appropriate by their primary treating medical team (patients can have received radiation or chemoradiation in addition to this 6 months course)
• Central expert reviewer must have determined the patient eligible for randomization after review of local genetic testing reports
• If mutation in BRCA1, BRCA2 or PALB2 was identified in tumor tissue and the patient has not previously undergone germline testing, the patient must agree to undergo germline testing
• Patient must be >= 21 days (three weeks) from their last treatment (including chemotherapy radiotherapy or surgery) but =< 84 days (twelve weeks) from their last treatment at the time of Step 1 randomization. Patients who have received neoadjuvant and/or adjuvant radiotherapy are eligible
• Patient must have recovered from any adverse events due to prior anti-cancer therapy (i.e., have no residual toxicities > grade 1 with the exception of alopecia and/or neuropathy)
• Leukocytes >= 3,000/mcL (obtained =< 28 days prior to Step 1 randomization)
• Absolute neutrophil count >= 1,500/mcL (obtained =< 28 days prior to Step 1 randomization)
• Platelets >= 100,000/mcL (obtained =< 28 days prior to Step 1 randomization)
• Hemoglobin >= 9.0 g/dL with no blood transfusion in the past 28 days (obtained =< 28 days prior to Step 1 randomization)
• Total bilirubin =< 1.5 institutional upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin =< 2.5 x ULN of the direct bilirubin (obtained =< 28 days prior to Step 1 randomization)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 institutional ULN (obtained =< 28 days prior to Step 1 randomization)
• Creatinine =< 1.5 institutional ULN OR calculated Cockcroft Gault creatinine clearance > 50 mL/min/1.73 m^2 (obtained =< 28 days prior to Step 1 randomization)
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patient must have the ability to understand the willingness to sign a written informed consent document, or have legally authorized representative provide authorization to participate
• STEP 1 (RANDOMIZATION) EXCLUSION CRITERIA
• Patient must have no evidence of recurrent or metastatic pancreatic cancer at the time of randomization as documented by baseline scans obtained =< 4 weeks prior to Step 1 randomization
• Patient must not have previously had evidence of progressive pancreatic cancer while receiving platinum-based therapy
• Patient must not be receiving any other investigational agents at the time of Step 1 randomization and while on protocol treatment
• Patient must not have any history of allergic reactions attributed to compounds of similar chemical or biological composition to olaparib
• Patient must not have any personal history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
• Patient must not have any uncontrolled gastrointestinal disorder that would, in the opinion of the investigator, interfere with the ingestion or absorption of olaparib
• Patient must not be pregnant or breast-feeding due the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 14 days prior to Step 1 randomization to rule out pregnancy. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 6 months after the last dose of protocol treatment for female patients and for 3 months after the last dose of protocol treatment for male patients. Patients must also not donate sperm while on protocol treatment and for 3 months after the last dose of protocol treatment. Patients must also not breast-feed while on protocol treatment and for 1 month after the last dose of protocol treatment
• Patient must not have resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT (QTc) prolongation > 500 ms, electrolyte disturbances, etc.) or have congenital long QT syndrome
• Concomitant use of known potent CYP3A4/5 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir is prohibited
• Patients who are being actively treated for an ongoing concurrent malignancy are ineligible, with the exception of those receiving adjuvant hormone therapies and those receiving topical therapies for skin cancers
• Patient must not have, in the opinion of the investigator, any other concurrent medical condition that would prevent the patient from complying with the study procedures
• Patient must not be considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
• Patient must not have had major surgery within 2 weeks prior to Step 1 randomization and patients must have recovered from any effects of any major surgery

Monotherapy Inclusion Criteria (Parts A and B)
• Histologically- or cytologically-confirmed advanced or metastatic malignancy, defined as:
• One of the following tumor types:
• Unresectable locally-advanced or metastatic non-small cell lung cancer (NSCLC), gastric/gastroesophageal (GE) junction carcinoma, cutaneous melanoma, head and neck squamous cell carcinoma (HNSCC), bladder cancer, cervical cancer, ovarian cancer, or triple negative breast cancer (TNBC)
• Lymphomas, including:
• cHL
• Diffuse large B-cell lymphoma (DLBCL)
• Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS)
• Lymphoma: Participants should have disease progression on or after treatment with standard therapies expected to provide benefit in the judgement of the investigator.
• cHL: Participants must have received at least 3 prior systemic therapies. Participants should have had disease recurrence or progression following brentuximab vedotin therapy or have been ineligible to receive brentuximab vedotin. Participants who have not received autologous stem cell transplant (SCT) must have refused or been deemed ineligible. Participants should have received or not be eligible to have received an anti-PD-1 agent.
• DLBCL: Participants must have received at least 2 prior systemic chemo-immunotherapy regimens, including an anti-CD20 agent and combination chemotherapy. Unless clinically contraindicated, participants should have had disease that has relapsed after or be refractory to intensive salvage chemotherapy, including autologous SCT.
• PTCL-NOS: Participants must have had at least 1 prior systemic therapy. Participants must have received or have been ineligible to receive the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy. Participants with CD30-positive disease must have received or be ineligible to receive brentuximab vedotin. Participants must have also received intensive salvage therapy (defined as combination chemotherapy ± autologous SCT) unless they refused or were deemed ineligible.
• Measurable disease defined as:
• Solid tumors: Measurable disease according to RECIST V1.1
• Lymphomas: Fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET) and measurable disease of ≥15 mm in the greatest transverse diameter by computed tomography (CT) scan, as assessed by the site radiologist.
• A representative archival tumor tissue sample should be available as follows: Participants must provide archived tumor tissue, if available, from the most recent biopsy (less than or equal to [≤] 12 months from screening). If archived tissue is not available, a fresh baseline tumor biopsy will be requested for any participant enrolled in Part B whose tumors are considered accessible and appropriate in the opinion of the investigator.
• ECOG Performance Status score of 0 or 1 Combination Inclusion Criteria (Part C)
• ECOG Performance Status score of 0 or 1
• NSCLC: histological or cytological confirmed metastatic disease. Participants must have received no prior anti-PD-1/PD-L1 therapy allowed.
• HNSCC: histological or cytological confirmed metastatic disease. Participants must have received no prior exposure to anti-PD-1/PD-L1 therapy.
• Cutaneous Melanoma: histological or cytological confirmed metastatic disease. Participants must not have received anti-PD-1/PD-L1 targeted therapy.
• Measurable disease by CT or magnetic resonance imaging (MRI) as defined by RECIST V1.1
• Participants must provide archival tumor tissue from the most recent biopsy (≤12 months from screening). If archival tissue is not available, a fresh baseline tumor biopsy that has not been previously irradiated is required for any participant whose tumors are considered accessible and appropriate in the opinion of the investigator. Combination Inclusion Criteria (Part D)
• Histologically- or cytologically-confirmed advanced stage cHL
• cHL patients that have failed standard of care for R/R disease including prior treatment with BV.
• FDG PET emission tomography avid and bidimensional measurable disease of at least 1.5 cm in longest axis as documented by radiographic technique
• ECOG performance status of ≤ 2
• Participants are required to have tumor tissue, if available, from the most recent biopsy (≤12 months from screening) prior to start of study treatment. If archival tissue is not available, a fresh screening tumor biopsy is required for any participant whose tumors are considered accessible and appropriate in the opinion of the investigator. Monotherapy Exclusion Criteria (Parts A and B)
• History of another malignancy within 2 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.
• Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment that has not been completed before the first dose of study drug within the timeframe as follows:
• Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks
• Palliative radiotherapy (≤2 weeks of radiotherapy to non-central nervous system [CNS] disease): ≤7 days prior to start of SEA-TGT
• Immune-checkpoint inhibitors: 4 weeks
• Monoclonal antibodies, antibody-drug conjugates (ADC), or radioimmunoconjugates: 4 weeks (2 weeks with documented disease progression)
• T-cell or other cell-based therapies: 12 weeks
• Known CNS metastases
• Participants with a history of CNS metastases are allowed if they have undergone treatment for the CNS disease, symptoms have resolved, and steroids have been discontinued.
• Leptomeningeal involvement by malignant disease is excluded regardless of prior treatment.
• Previous allogeneic stem cell transplant (SCT). Participants with prior autologous SCT may be eligible if they are >100 days from autologous SCT and fulfill all other inclusion criteria.
• Prior use of any anti-TIGIT mAb.
• Participants with a condition requiring systemic treatment with either corticosteroids (greater than [>]10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids and adrenal replacement steroid doses >10 mg daily prednisone or equivalents are permitted in the absence of active immune disease.
• Known hypersensitivity to any excipient contained in the drug formulation of SEA-TGT Combination Exclusion Criteria (Part C)
• History of another malignancy within 2 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.
• Active, non-infectious pneumonitis, pulmonary fibrosis, or known history of immune mediated pneumonitis.
• Previous therapy with an anti-PD-1 or anti-PD-L1 inhibitor.
• Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment that has not been completed before the first dose of study drug within the timeframe as follows:
• Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks
• Palliative radiotherapy (≤2 weeks of radiotherapy to non-CNS disease): ≤7 days prior to start of SEA-TGT.
• Immune-checkpoint inhibitors: 4 weeks
• Monoclonal antibodies, ADC, or radioimmunoconjugates: 4 weeks (2 weeks with documented disease progression)
• T-cell or other cell-based therapies: 12 weeks
• Known active CNS metastases.
• Participants with a history of CNS metastases are allowed if they have undergone treatment for the CNS disease, symptoms have resolved, and steroids have been discontinued.
• Leptomeningeal involvement by malignant disease is excluded regardless of prior treatment.
• Known hypersensitivity to any excipient contained in the drug formulation of SEA-TGT or sasanlimab
• Participants with active known or suspected autoimmune disease or significant autoimmune-related toxicity from prior immuno-oncology-based therapy (prior autoimmune colitis, pneumonitis, transaminitis); Participants with vitiligo, controlled type 1 diabetes mellitus, residual hypothyroidism requiring hormone replacement, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• History of interstitial lung disease
• Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids and adrenal replacement steroid doses >10 mg daily prednisone or equivalents are permitted in the absence of active immune disease.
• Prior use of any anti-TIGIT mAb Combination Exclusion Criteria (Part D)
• History of another malignancy within 2 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death.
• Chemotherapy, radiotherapy, biologics, and/or other antitumor treatment that has not been completed before the first dose of study drug within the timeframe as follows:
• Chemotherapy, small molecule inhibitors, radiation, and/or other investigational anticancer agents (excluding investigational monoclonal antibodies): 2 weeks
• Palliative radiotherapy (≤2 weeks of radiotherapy to CNS disease): ≤7 days prior to start of SEA-TGT
• Immune-checkpoint inhibitors: 4 weeks
• Monoclonal antibodies, ADC (except brentuximab vedotin), or radioimmunoconjugates: 4 weeks (2 weeks with documented disease progression)
• T-cell or other cell-based therapies: 12 weeks
• Known active CNS involvement by lymphoma
• Previous allogeneic SCT. Participants with prior autologous SCT may be eligible if they are >100 days from autologous SCT and fulfill all other inclusion criteria.
• Prior use of any anti-TIGIT mAb.
• Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids and adrenal replacement steroid doses >10 mg daily prednisone or equivalents are permitted in the absence of active immune disease.

• Participant must be at least 18 years of age
• Participants with at least one measurable lesion according to the RECIST v1.1 criteria that has not been irradiated (ie, newly arising lesions in previously irradiated areas are accepted).
• Participants with ECOG performance status 0 to 1.
• Evidence of metastatic disease.
• Expression of CEACAM 5 by centrally assessed IHC assay.
• Male and female participants willing to comply with contraceptive use consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Cohort A: mBC
• Histological or cytologic diagnosis of breast cancer.
• Have received at least 2 prior cytotoxic chemotherapy regimens for non-TNBC tumor type or at least 1 for TNBC tumor type but not more than 4 in the locally recurrent or metastatic setting. Cohorts B and C: mPAC
•Have confirmed diagnosis of pancreatic ductal adenocarcinoma. Cohort B: mPAC:
•Have documented radiographic progression or documented intolerance after at least 1 prior systemic chemotherapy line which included either gemcitabine (or relapsed within 6 months of completion of gemcitabine adjuvant therapy) or a 5-fluorouracil based regimen (including capecitabine) but no more than 2 prior chemotherapy lines for locally advanced/metastatic disease. Cohort C: mPAC
•Have documented radiographic progression or documented intolerance after 1st line fluoropyrimidine-containing chemotherapy (or relapsed within 6 months of completion of chemotherapy as adjuvant therapy) for locally advanced/metastatic disease. Participants are excluded from the study if any of the following criteria apply:
• Medical condition requiring concomitant administration of a medication with a narrow therapeutic window, that is metabolized by cytochrome P450 (CYP450), and for which a dose reduction cannot be considered.
• Medical conditions requiring concomitant administration of strong CYP3A inhibitor, unless it can be discontinued at least 2 weeks before the first administration of study intervention.
• Life expectancy less than 3 months.
• Untreated brain metastases or history of leptomeningeal disease.
• Significant concomitant illness
• History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment.
• History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or active hepatitis A, B or C infection.
• Non-resolution of any prior treatment-related toxicity to • Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy.
• Use of contact lenses. Participants using contact lenses who are not willing to stop wearing them for the duration of the study intervention are excluded.
• Concurrent treatment with any other anti cancer therapy.
• Washout period before the first administration of study intervention of less than 3 weeks or less than 5 times the half-life, whichever is shorter, for prior antitumor therapy (chemotherapy, targeted agents, immunotherapy and radiotherapy, or any investigational treatment).
• Any prior therapy targeting CEACAM5.
• Prior maytansinoid DM4 treatment (ADC).
• Any major surgery within the preceding 2 weeks of the first study intervention administration.
• Previous enrollment in this study or current participation in any other clinical study involving an investigational study treatment or any other type of medical research.
• Poor renal function
• Poor hepatic function
• Poor bone marrow function Cohort C: mPAC
•Any previous systemic therapy with taxane or gemcitabine (for Cohort C only). The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

1. Able and willing to participate and comply with all study requirements and provide signed and dated informed consent prior to initiation of any study procedures; 2. Histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancy. 1. Stages 1 and 2: Subject must have received, have been intolerant to, have been ineligible for, or have declined all treatment known to confer clinical benefit with the exception of subjects enrolled in combination cohorts with a PD-1i, where a PD-1i is approved by the local regulatory agencies 2. Stage 3: This stage may enroll subjects with the following cancers: • 3L/4L PD-(L)1-naïve, platinum-resistant ovarian cancer 3. Stage 4: This stage may enroll subjects with the following cancers:
• 2L/3L ccRCC. Subjects must have progressed on or after treatment with an anti-PD-(L)1 agent in their most recent prior line of therapy
• 2L-4L TNBC. Subjects must have progressed on or after treatment with a prior anti-PD-(L)1 therapy
• 1L, PD-(L)1-naïve, PD-L1+; combined positive score (CPS) ≥ 1% HNSCC
• 3L/4L, PD-(L)1-naïve, platinum-resistant ovarian cancer
• 2L/3L NSCLC; Subjects must have progressed on or after treatment with platinum-based chemotherapy and an anti-PD-(L)1-containing therapy. The anti-PD-(L)1 agent must have been a part of the most recent prior line of therapy. Subjects with EGFR mutations and ALK rearrangements will be excluded. Subjects with other targetable genomic aberrations for which FDA approved therapies exist must have received appropriate FDA-approved targeted therapy
• 2L/3L cSCC; Subjects must have progressed on or after treatment with an anti-PD-(L)1 agent in their most recent prior line of therapy
• 2L-4L PD-(L)1-naïve UPS and LPS
• 2L/3L HNSCC. Subjects must have progressed on or after treatment with platinum-based chemotherapy and an anti-PD-(L)1-containing therapy. The anti-PD-(L)1 agent must have been a part of the most recent prior line of therapy.
• 2/3L biliary tract cancer (BTC), including intra-and extra-hepatic biliary duct cancer and cancer of the gallbladder. Subjects must have progressed on or after gemcitabine/cisplatin (Gem/Cis) and an anti-PD-(L)1 therapy in the metastatic setting. Must have PD-(L)1 inhibitor resistance. Subjects with FGFR and IDH1 mutations must have progressed on or after targeted therapies for these mutations. 3. Measurable disease, according to the RECIST version 1.1, that has objectively progressed since (or on) previous treatment as assessed by the Investigator; 4. ≥ 18 years of age; 5. Eastern Cooperative Oncology Group performance status 0 or 1; 6. Predicted life expectancy of ≥ 3 months; 7. Have specified laboratory values (obtained ≤ 28 days prior to first dose) in accordance with the study protocol; 8. For women of childbearing potential (WOCBP): negative serum pregnancy test during the Screening period and a negative urine pregnancy test up to 24 hours in advance of C1D1 9. WOCBP and males whose partners are WOCBP must agree to use a highly effective method of birth control throughout their participation and for 5 months following the last study drug administration. 1. Concurrent anticancer treatment, either FDA approved or investigational, for the cancer being evaluated in this study or for prior malignancies. A past history of other malignancies is allowed as long as the subject is not receiving treatment other than hormonal therapy and, in the judgment of the Investigator, is unlikely to have a recurrence. Of note, concurrent malignancies that do not require treatment and are clinically stable are allowed 2. Prior infusion of JTX-8064, LILRB2, or ILT4-directed therapy; 3. The therapies listed below within the specified timeframe: 1. Immunotherapy or biologic therapy < 28 days prior to planned C1D1 or 5 half-lives, whichever is shorter 2. Chemotherapy < 21 days prior to planned C1D1, or < 42 days for mitomycin or nitrosoureas or 5 half-lives, whichever is shorter 3. Targeted small molecule therapy < 14 days or 5 half-lives, whichever is shorter, prior to planned C1D1 4. Radiation therapy < 21 days prior to planned C1D1. Exception: Limited (e.g., pain palliation) radiation therapy is allowed prior to and during study drug administration as long as there are no acute toxicities, any AE due to prior radiation therapy has recovered to < Grade 2, and the radiation is not administered to a target lesion 4. Symptomatic or uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation (brain metastases that are stable and asymptomatic after prior treatment will be allowed); 5. Women who are pregnant or breastfeeding or who plan to become pregnant/breastfeed while on study; men who plan to father children during the study 6. Live vaccines ≤ 30 days of C1D1

• Patients have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or circulating tumor deoxyribonucleic acid (DNA).
• Participants must have a histological or a cytologically proven diagnosis of locally advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Have adequate organ function.
• Have discontinued all previous treatments for cancer with resolution of any significant ongoing adverse events (AEs).
• Must be able to swallow capsule/tablet.
• Agree and adhere to contraceptive use, if applicable.
• For some parts of the study, histologically or cytologically confirmed Stage IIIB-IIIC or Stage IV NSCLC that is previously untreated in the advanced/metastatic setting and not suitable for curative intent radical surgery or radiation therapy.
• For some parts of the study, patients must be PD-L1 positive, (TPS greater than or equal to 1%)
• Disease suitable for local therapy administered with curative intent.
• Have an active, ongoing, or untreated infection.
• Have a serious pre-existing medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
• Have a serious cardiac condition.
• Have a second active primary malignancy or have been diagnosed and/or treated for an additional malignancy within 3 years prior to enrollment.
• Have symptomatic central nervous system (CNS) malignancy or metastasis and/or carcinomatous meningitis. Patients with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids in excess of 10 milligrams (mg) per day prednisone/prednisolone (or equivalent) and their disease is asymptomatic and radiographically stable for at least 30 days. This only applies to some parts of the study.
• Have received prior treatment with any KRAS G12C small molecule inhibitor, except in certain scenarios where such prior therapy is allowed as per protocol.
• Patients treated with drugs known to be strong inhibitors or inducers of cytochrome P450 (CYP)3A may be excluded.
• The following patients will be excluded from some parts of the study:
• Experienced certain serious side effects with prior immunotherapy.
• Have an active autoimmune disease that has required systemic anti-autoimmune treatment in the past 2 years.
• Have received a live vaccine within 30 days prior to the first dose of study drug.
• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 180 days after the last dose of study medication.
• Known allergic reaction against any of the components of the study treatments.

• Participant must be neurologically normal, defined as free of unstable neurologic and psychiatric disease as confirmed by a normal neurologic examination at screening
• Participant (GBCA-exposed or controls) agrees to undergo unenhanced magnetic resonance imaging (UE-MRI) of the brain at enrollment and at the end of the observation period (5 years)
• Participants should have at least 1 of the following indications: a) Medium to high risk for breast cancer or dense breasts undergoing breast cancer screening with MRI, b) Elevated prostate-specific antigen (PSA) and under active diagnostic surveillance for prostate cancer, c) Chronic liver disease (eg, liver cirrhosis limited to Child class A, post-hepatitis chronic hepatopathy, or primary sclerosing cholangitis) for surveillance of hepatocellular carcinoma development, d) Low-grade colorectal cancer or neuroendocrine tumor undergoing screening for liver metastases or e) Branch-duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas (maximum size ≤2 cm) undergoing imaging surveillance. In addition, for participants in the GBCA Arms only:
• Each participant should be likely to undergo ≥5 GBCA-enhanced MR examinations with the same GBCA at least annually throughout the 5-year study duration
• Prospective participants with up to 3 well documented GBCA administrations prior to study screening are acceptable, provided that the imaging was performed with the same GBCA as the one to be prospectively used in the study. If the GBCA used cannot be identified, he/she cannot be enrolled. For the Control Arm:
• Participants who never had and are not likely to receive any GBCA injection during the course of the study
• Each control participant must be willing to undergo UE-MRI of the brain at baseline and at Year 5. In Years 1 to 4, the control participants will undergo their clinically indicated UE-MRIs, computed tomography (CT), ultrasound, or X-ray procedures
• As evidenced by history or determined in the neurologic exam at screening, concurrent neurological and/or psychiatric disease (or treatments) that could influence the results of the study's motor and cognitive tests (e.g. Cerebrovascular disease, Multiple sclerosis, Neurodegenerative disease, Malignant disease other than listed in indications, Carcinoid tumors, Epilepsy, Prior neurosurgery, Psychotic disorders or any prior psychotic episode not otherwise specified
•any documented prior history of chronic schizophrenia, Remittent or current medically confirmed major depressive disorder or bipolar disorder, History of long-term major depression or bipolar affective disorder with an active episode in the past 2 to 5 years, Neurodevelopmental disorders (eg, trisomy 21), Uncontrolled severe migraine, Uncontrolled or controlled anxiety or depression within 6 months before enrollment, Screening scores of ≤24 on the MMSE and/or ≥11 on the Hospital Anxiety and Depression Scale (HADS)).
• Prior, planned, or ongoing chemotherapy or brain irradiation
• Use of concomitant medication(s) affecting neuro-cognitive or motor function
• Substance or alcohol abuse as determined by the investigator
• Alcoholic cirrhosis
• Renal disease, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2
• History of environmental/occupational/other exposure to one or more chemicals that may affect cognitive and/or motor function, including, but not limited to, heavy metals (arsenic [As], cadmium [Cd], lead [Pb], manganese [Mn], and mercury [Hg]), pesticides, solvents, or carbon monoxide.
• Clinical indications requiring >1 contrast enhanced magnetic resonance imaging (CE-MRI) every 6 months
• Pregnant or nursing (lactating) women
• Presence of any metal-containing joint implants/prostheses In addition, for participants in either of the GBCA Arms only:
•Receipt of a GBCA or generic prior to study entry other than the specific GBCA to be administered during the course of the study. For participants in the Control Arm only:
• Participants with any previous exposure to a GBCA.
• Participants with any contraindication to UE-MRI examinations.

• Patients must be =< 50 years of age at the time of enrollment
• Patients with newly diagnosed RMS of any subtype, except adult-type pleomorphic, based upon institutional histopathologic classification are eligible to enroll on the study based upon stage, group, and age, as below. FOXO1 fusion status must be determined by week 4 (day 28) of therapy. RMS types included under embryonal RMS (ERMS) include those classified in the 1995 International Classification of Rhabdomyosarcoma (ICR) as ERMS (classic, spindle cell, and botryoid variants), which are reclassified in the 2020 World Health Organization (WHO) Classification as ERMS (classic, dense and botryoid variants) and spindle cell/sclerosing RMS (encompassing the historical spindle cell ERMS variant and the newly recognized sclerosing RMS variant). Classification of alveolar RMS (ARMS) in the 2020 WHO Classification is the same as in the ICR and includes classic and solid variants
• ERMS
• Stage 4, group IV, >= 10 years of age
• ARMS
• Stage 4, group IV Patients will be eligible to remain on protocol therapy based upon stage, group, and age
• Bone marrow metastatic disease is based on morphologic evidence of RMS based on hematoxylin and eosin (H&E) stains. In the absence of morphologic evidence of marrow involvement on H&E, patients with bone marrow involvement detected ONLY by flow cytometry, reverse transcriptase (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or immunohistochemistry will NOT be considered to have clinical bone marrow involvement for the purposes of this study
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment):
• Age; Maximum serum creatinine (mg/dL)
• 1 month to < 6 months; 0.4 mg/dL (male); 0.4 mg/dL (female)
• 6 months to < 1 year; 0.5 mg/dL (male); 0.5 mg/dL (female)
• 1 to < 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
• 2 to < 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
• 6 to < 10 years; 1 mg/dL (male); 1 mg/dL (female)
• 10 to < 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
• 13 to < 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
• >= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment)
• If there is evidence of biliary obstruction by tumor, then total bilirubin must be < 3 x ULN for age
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Patients with evidence of uncontrolled infection are not eligible
• RMS that is considered a second malignancy and previous cancer(s) that were treated with chemotherapy and/or radiation. Surgical resection alone of previous cancer(s) is allowed
• Patients with central nervous system involvement of RMS as defined below:
• Malignant cells detected in cerebrospinal fluid
• Intra-parenchymal brain metastasis separate and distinct from primary tumor (i.e., direct extension from parameningeal primary tumors is allowed).
• Diffuse leptomeningeal disease
• Patients who have received any chemotherapy (excluding steroids) and/or radiation therapy for RMS prior to enrollment.
• Note: the following exception:
• Patients requiring emergency radiation therapy for RMS. These patients are eligible, provided they are consented to ARST2031 prior to administration of radiation
• Note: Patients who have received or are receiving chemotherapy or radiation for non-malignant conditions (e.g. autoimmune diseases) are eligible. Patients must discontinue chemotherapy for non-malignant conditions prior to starting protocol therapy
• Vincristine and vinorelbine are sensitive substrates of CYP450 3A4 isozyme. Patients must not have received drugs that are moderate to strong CYP3A4 inhibitors and inducers within 7 days prior to study enrollment
• Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
• Lactating females who plan to breastfeed their infants
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation