Here are the studies that match your search criteria. If you are interested in participating, please reach out to the contact listed for the study. If no contact is listed, contact us and we'll help you find the right person.
Study of DF9001 in Patients With Advanced Solid Tumors
DF9001-001 is a study of a new molecule that targets natural killer (NK) cells and T-cell
activation signals to specific receptors on cancer cells. The study will occur in two phases.
The first phase will be a dose escalation phase, enrolling patients with various types of
solid tumors that express epidermal growth factor receptor (EGFR). The second phase will
include a dose expansion using the best dose selected from the first phase of the study.
Multiple cohorts will be opened with eligible patients having selected solid tumors
(monotherapy and in combination with pembrolizumab).
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05597839
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
General (applies to all cohorts)
1. Signed written informed consent.
2. Male or female patients aged ≥ 18 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry
and an estimated life expectancy of at least 3 months.
4. Adequate hematological function per protocol.
5. Adequate hepatic function per protocol.
6. Adequate renal function per protocol.
7. Participation in the use of contraception during the study, and for 150 days after the
last dose of study drug for women of child-bearing potential (WOCBP) and 30 days after
the last dose of study drug for male patients, as defined by the Clinical Trial
Facilitation Group (CTFG) guidelines.
Inclusion Criteria:
Dose Escalation (Monotherapy)
1. Histologically proven locally advanced or metastatic solid tumors of epithelial origin
that (1) have squamous NSCLC or HNSCC, (2) has documented EGFR protein expression or
EGFR amplification or polysomy in their medical history from previous testing, or (3)
test positive for EGFR expression via archival or fresh biopsy tissue prior to study
enrollment using a validated immunohistochemistry (IHC) assay.
2. Evidence of objective disease, but participation does not require a measurable lesion.
Inclusion Criteria:
Head and Neck Squamous Cell Carcinoma (HNSCC) Expansion Cohorts
1. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
2. Histologically documented relapsed or metastatic HNSCC. Primary tumor locations
include oropharynx, oral cavity, hypopharynx, or larynx. Patients may not have a
primary tumor site of nasopharynx (any histology).
3. Patients must have radiographic disease progression while on or after having received
both platinum-based or fluoropyrimidine-based chemotherapy and an anti-PD-(L)1
therapy, administered either concurrent or sequentially.
4. Willing and able to provide the most recently available tissue blocks representing
tumor biopsy obtained prior to treatment initiation. If recent tissue is not
available, then a newly obtained baseline biopsy of an accessible tumor is required.
Note that "recent" is defined as no intervening systemic anticancer therapies from the
time of the last treatment of the prior therapy until screening for this trial.
5. Willing to undergo on-treatment biopsies, if safe and medically feasible.
Inclusion Criteria:
Renal Cell Carcinoma (RCC) Expansion Cohorts
1. Patients must have radiographic progression during treatment or after completing
treatment for advanced (recurrent/unresectable/metastatic) disease or be intolerant to
prior therapy.
2. Histologically documented relapsed or metastatic RCC that has documented EGFR
expression or EGFR gene amplification or polysomy in their medical history from
previous testing or test positive for EGFR expression (Section 6.2 EGFR Positivity)
via archival (only if a block is available) or fresh biopsy tissue prior to study
enrollment using a validated IHC assay. Cytology specimens cannot be used for the
purpose of defining EGFR expression to meet eligibility.
3. Patients with clear cell RCC (ccRCC) must have radiographic progression after receipt
of one of the following combination regimens as the preceding line of therapy:
1. PD-1/PD-L1-targeting mAb with or without a VEGFR-TKI.
2. PD-1-targeting mAb with a CTLA-4 monoclonal.
3. Patients with non-clear cell RCC (nccRCC) are not required to have received prior
therapy in the metastatic setting.
4. Patients with RCC in general are not required to have received TKI therapy (eg,
axitinib, cabozantinib, lenvatinib + everolimus, tivozanib).
4. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
5. Willing and able to provide the most recently available tissue blocks representing
tumor biopsy obtained prior to treatment initiation. If recent tissue is not
available, then a newly obtained baseline biopsy of an accessible tumor is required.
Note that "recent" is defined as no intervening systemic anticancer therapies from the
time of the last treatment of the prior therapy until screening for this trial.
6. Willing to undergo on-treatment biopsies, if safe and medically feasible.
Inclusion Criteria:
Non-Small Cell Lung Cancer (NSCLC) Expansion Cohorts
1. Histologically confirmed NSCLC meeting stage criteria for stage IIIB, stage IIIC, or
stage IV NSCLC disease with or without actionable genomic alterations (AGA) (per the
7th IASLC classification of NSCLC), or recurrent disease.
1. Patients with squamous NSCLC do not require EGFR testing as part of this study to
be eligible.
2. Non-squamous NSCLC patients who have documented EGFR expression or EGFR gene
amplification or polysomy in their medical history from previous testing or test
positive for EGFR expression (Section 6.2 EGFR Positivity) via archival (only if
a block is available) or fresh biopsy tissue prior to study enrollment using a
validated IHC assay.
3. Patients with stage IIIB or IIIC must be ineligible for local therapies with
curative intent (eg, radiotherapy or surgery).
2. Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST
1.1.
3. Patients must have recurrent or progressive disease during or after first line
combination therapy with checkpoint inhibitors and platinum-based chemotherapy OR must
have recurrent or progressive disease within 6 months after completing platinum- based
chemotherapy for local disease, including those with actionable genetic alterations.
They must not have received any subsequent lines of therapy.
4. Status for actionable mutations (EGFR, ALK, ROS1, RET, etc.) must be known (when
testing is available as per country/region standard of care practices); patients with
actionable mutations must have received and progressed on, have been intolerant to, or
not be a candidate for standard TKIs (as available per country/region standard of care
practices).
5. Willing and able to provide the most recently available tissue blocks representing
tumor biopsy obtained prior to treatment initiation. If recent tissue is not
available, then a newly obtained baseline biopsy of an accessible tumor is required.
Note that "recent" is defined as no intervening systemic anticancer therapies from the
time of the last treatment of the prior therapy until screening for this trial.
6. Willing to undergo on-treatment biopsies, if safe and medically feasible.
Exclusion Criteria:
1. Patients must not have had chemotherapy, radiotherapy (other than palliative bone-
directed radiotherapy, as described in in exclusion criterion #2), or major surgery,
or received another investigational agent within 28 days or 5 half-lives of the drug
(if known), whichever is shorter, before the start of study treatment.
2. Received prior radiotherapy within 2 weeks of start of study intervention, or has
radiation-related toxicities, requiring corticosteroids.
a. Note: Two weeks or fewer of palliative radiotherapy for non-central nervous system
(CNS) disease is permitted. The last radiotherapy treatment must have been performed
at least 7 days before the first dose of study intervention.
3. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study intervention.
4. Concurrent anticancer treatment (eg, cytoreductive therapy, radiotherapy [except for
palliative bone-directed radiotherapy, which is not a target lesion], immune therapy,
or cytokine therapy [except for erythropoietin]), major surgery (excluding prior
diagnostic biopsy), concurrent systemic therapy with steroids or other
immunosuppressive agents, or use of any investigational drug within 28 days or 5
half-lives of the drug (if known), whichever is shorter, before the start of study
treatment. Short-term administration of systemic steroids (eg, for allergic reactions
or the management of irAEs) is allowed. Note: Patients receiving bisphosphonate or
denosumab are eligible, provided treatment was initiated at least 14 days before the
first dose of DF9001.
5. Previous malignant disease other than the target malignancy to be investigated in this
study within the last 3 years. Exceptions (eg, basal or squamous cell carcinoma of the
skin, or cervical carcinoma in situ) can be considered on a case-by-case basis, in
consultation with the Medical Monitor.
6. Life expectancy of less than 6 months.
7. Receipt of any organ transplantation, including autologous or allogeneic stem-cell
transplantation.
8. Significant acute or chronic infections (including historic positive test for human
immunodeficiency virus [HIV], or active or latent hepatitis B or active hepatitis C
tested during the screening window). If HBsAg is negative and the anti-hepatitis B
core antibody is positive, then hepatitis B viral DNA load must be undetectable.
9. Preexisting autoimmune disease (except for patients with vitiligo) needing treatment
with systemic immunosuppressive agents for more than 28 days within the last 3 years,
or clinically relevant immunodeficiencies (eg, dysgammaglobulinemia or congenital
immunodeficiencies). Patients with a history of immune-related endocrinopathies (eg,
hypothyroidism, type 1 diabetes mellitus [TIDM], and adrenal insufficiency) that are
stable on hormone replacement therapy may be eligible for this study.
10. Patients with a known medical history that may place them at risk of known toxicities
of EGFR blockade.
1. History of or ongoing keratitis, ulcerative keratitis, or corneal perforation.
2. History of cardiopulmonary arrest unless this was caused by an acute, reversible
etiology that is no longer present.
3. History of or ongoing pulmonary fibrosis or interstitial lung disease.
11. Known severe hypersensitivity reactions to mAbs (≥ Grade 3 of the NCI-CTCAE v5.0), any
history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partly
controlled asthma).
12. Persisting toxicity related to prior therapy >Grade 1 NCI-CTCAE v5.0; however,
alopecia ≤Grade 2, endocrinopathies ≤Grade 2, and sensory neuropathy ≤ Grade 2 is
acceptable.
13. Patients who have received an anti-PD-(L)1 as a previous line of therapy that have
experienced either of the following:
1. a Grade 3 or Grade 4 drug-related toxicity.
2. a Grade 2 drug-related toxicity that impacted either the lungs, cardiac, or the
nervous system, caused by the administration of the anti-PD-(L)1.
14. Received any prior immunotherapy and was discontinued from that treatment due to a
Grade 3 or higher irAE (except endocrine disorders that can be treated with
replacement therapy) or was discontinued from that treatment due to Grade 2
myocarditis or recurrent Grade 2 pneumonitis.
15. A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required.
16. Has received a live or live-attenuated vaccine within 30 days prior to the first dose
of study intervention. Administration of killed vaccines are allowed.
17. Pregnancy or lactation in females during the study.
18. Known alcohol or drug abuse.
19. Serious cardiac illness or medical conditions, including but not limited to:
1. History of New York Heart Association class III or IV heart failure or systolic
dysfunction (left ventricular ejection fraction [LVEF] <55%).
2. High-risk uncontrolled arrhythmias (eg, tachycardia with a heart rate >100/min at
rest).
3. Significant ventricular arrhythmia (ventricular tachycardia) or higher-grade
atrioventricular (AV) block (eg, AV-block, second degree AV block Type 2 [Mobitz
2], or third-degree AV-block).
4. Angina pectoris requiring anti-anginal medication.
5. Clinically significant valvular heart disease.
6. Evidence of transmural infarction on electrocardiograms (ECGs).
7. Poorly controlled hypertension (defined as systolic >160 mm Hg or diastolic >100
mm Hg).
8. Clinically relevant uncontrolled cardiac risk factors, clinically relevant
pulmonary disease, or any clinically relevant medical condition in the opinion of
the Investigator that may limit participation in this study.
9. Severe dyspnea at rest due to complications of advanced malignancy or requiring
supplementary oxygen therapy.
20. All other significant diseases (eg, inflammatory bowel disease), which, in the opinion
of the Investigator, might impair the patient's ability to participate.
21. Any psychiatric condition that would prohibit the understanding or rendering of
informed consent.
22. Legal incapacity or limited legal capacity.
23. Incapable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the ICF and in this protocol.
24. Has received radiation therapy to the lung that is >30 Gy within 6 months of the first
dose of study treatment (for NSCLC cohorts only).
25. Patients with brain metastases, unless all of the following criteria are met:
1. CNS lesions are asymptomatic, previously treated and no active therapy is
required (ie, no corticosteroids for edema),
2. Radiologically stable (ie, without evidence of progression) for at least 4 weeks
as confirmed by repeat imaging performed during the study screening, are
clinically stable and have not required steroid treatment for at least 14 days
before the first dose of study intervention.
3. Imaging demonstrates stability of disease 28 days from last treatment for CNS
metastases.
26. Active autoimmune disease that has required systemic treatment in past 2 years except
replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid).
27. Patients with leptomeningeal disease are excluded.
28. History of (noninfectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease.
29. Active infection requiring systemic therapy.
30. Severe hypersensitivity (≥Grade 3) to pembrolizumab, and/or any of its excipients.
Solid Tumor, Adult, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Protonix Treatment of Maintenance of Healing in Pediatric Participants Aged 1-11 Years and 12-17 Years
The purpose of this study is to explore the outcomes, tolerability and safety of 2 different
doses of oral pantoprazole (full healing dose, half healing dose), assigned based upon
weight, for the maintenance of healing of erosive esophagitis in pediatric participants aged
1 to 17 years with endoscopically-confirmed, healed erosive esophagitis.
Thomas Ratchford
All
1 Year to 17 Years old
Phase 2
This study is NOT accepting healthy volunteers
NCT04821310
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Participants must have a documented erosive lesion with an Los Angeles (LA) Grade of A
to D prior to starting Proton Pump Inhibitor treatment:
• Capable of giving signed informed consent/assent
• Willingness and ability of the participant or parent/legal guardian to complete the
eDiary
• Willing and able to comply with all scheduled visits, treatment plan, laboratory
tests, lifestyle considerations, and other study procedures, including the use of the
eDiary.
• Male and female participants aged 1 to 17 years.
• Minimum body weight 7 kilogram and weight at least at the 5th percentile per the
Center for Disease Control standard age and weight chart, for the participant's age.
• To be considered a female of non childbearing potential, the participant must meet at
least 1 of the following criteria :
• Premenarchal: The investigator (or other appropriate staff) must discuss the
participant's premenarchal status with the participant and parent/legal guardian at
office visits and during telephone contacts, as participants who achieve menarche
during the study would no longer be considered "female participants of non
childbearing potential" and must comply with the protocol requirements applicable to
women of childbearing potential.
Exclusion Criteria:
• Previous administration of an investigational drug or vaccine within 30 days (or as
determined by the local requirement) or 5 half-lives preceding the first dose of study
intervention used in this study (whichever is longer).
• Children that may be at high risk from procedural sedation should be carefully
evaluated. Participants with a history of complications during prior procedural
sedation
• History or presence of upper gastrointestinal anatomic or motor disorders
• Family history of malignant hyperthermia
• Known hypersensitivity to any Proton Pump Inhibitor, including pantoprazole or to any
substituted benzimidazole or to any of the excipients.
• Any disorder requiring chronic (daily) use of warfarin, heparin, other anticoagulants,
methotrexate, atazanavir or nelfinavir, clopidogrel, or potent inhibitors or inducers
of CYP2C19 (eg, phenytoin, sulfamethoxazole, valproic acid, carbamazepine, and
griseofulvin).
• Serum creatine kinase levels >3 x upper limit of normal.
• Known history of human immunodeficiency virus or clinical manifestations of acquired
immune deficiency syndrome.
• Active malignancy of any type, or history of a malignancy. Participants with a history
of malignancies that have been surgically removed or eradicated by irradiation or
chemotherapy and who have no evidence of recurrence for at least 5 years before
Screening are acceptable.
• Diagnosed as having or has received treatment for esophageal, gastric, pyloric
channel, or duodenal ulceration within 30 days before the Screening visit.
• Alanine aminotransferase or blood urea nitrogen >2.0 upper limit of normal or
estimated creatinine >1.5 X upper limit of normal for age or any other laboratory
abnormality considered by the Investigator to be clinically significant within 14 days
before the Baseline Visit (Day 1).
• Other acute or chronic medical or psychiatric condition including recent (within the
past year) or active suicidal ideation or behavior or laboratory abnormality that may
increase the risk associated with study participation or study intervention
administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the participant inappropriate for entry into
this study.
• Has, in the Investigator's opinion, a serious chronic condition (eg, diabetes,
epilepsy), which is either not stable or not well controlled and may interfere with
the conduct of the study.
• Has any condition possibly affecting drug absorption (eg, gastrectomy).
Prior or Concomitant Therapy:
• Frequent, repeated use of oral or parenteral glucocorticoids (eg, prednisone,
prednisolone, dexamethasone). Steroid inhalers and topical steroids may be used.
• Pregnant female participants; breastfeeding female participants.
• Is unwilling or unable to comply with the Lifestyle Considerations section
A Multi-center, Single-arm Trial Exploring the Safety and Clinical Effectiveness of RBX2660 Administered by Colonoscopy to Adults With Recurrent Clostridioides Difficile Infection (CDI-SCOPE)
This trial will be initiated to explore whether RBX2660 (REBYOTA®) could be suitable for
administration by the practice of colonoscopy. More specifically, the purpose of this trial
is to explore the safety and clinical effectiveness of RBX2660 when delivered by colonoscopy
to adults with rCDI. The experience of physicians will be documented through a
physician-experience questionnaire to explore the usability of RBX2660 in clinical practice
for colonoscopic administration. Furthermore, to explore the patient-experience of RBX2660
treatment, each trial participant will be offered to undergo a structured interview.
Nasia Safdar, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05831189
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• have documented evidence of rCDI (≥1 recurrence after a primary CDI episode)
• be undergoing antibiotic treatment for the qualifying rCDI episode that was diagnosed
by a stool test for the presence of toxigenic C. difficile or C. difficile toxin
• be eligible for FMT as judged by the investigator or current treatment guidelines for
rCDI in the US
• be a candidate for colonoscopy as judged by the investigator
Exclusion Criteria:
• Use or planned use of systemic antibiotics for an indication other than the qualifying
rCDI episode.
• Current uncontrolled chronic diarrhea not related to CDI.
• Receipt of CDI vaccine or treatment with CDI monoclonal antibodies within the past 12
months before screening.
• Evidence of active, severe, or fulminant colitis, diagnosis of toxic megacolon or have
a current colostomy or ileostomy
Clostridium Difficile Infection Recurrence, Enterocolitis due to Clostridium difficile, Other, Infections, Immune System & Allergies, Digestive Health & Liver Disease
KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors (FIT-001)
This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess
KO-2806, a farnesyl transferase inhibitor (FTI), as a monotherapy and in combination, in
adult patients with advanced solid tumors.
Justine Bruce, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT06026410
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• At least 18 years of age.
• Histologically or cytologically confirmed advanced solid tumors
• Arm #1 (Monotherapy): HRAS-mutant and/or amplified tumors (any solid tumor type);
HRAS overexpression (only for HNSCC tumors); KRAS and/or NRAS, and/or HRAS-mutant
and/or amplified NSCLC or CRC; KRAS-mutant and/or amplified PDAC
• Arm #2 (Combination): Must have received at least 1 prior systemic therapy with
IO-based treatment for locally advanced or metastatic RCC with predominantly
clear cell subtype
• Arm #3 (Combination): Must have KRAS G12C-mutant locally advanced or metastatic
NSCLC and have received at least 1 prior systemic therapy for advanced or
metastatic NSCLC
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Karnofsky Performance Status of 70 or higher with no clinically significant
deterioration over the previous 2 weeks.
• Acceptable liver, renal, endocrine, and hematologic function.
• Other protocol-defined inclusion criteria may apply.
Exclusion Criteria:
• Ongoing treatment with certain anticancer agents.
• Prior treatment with an FTI or HRAS inhibitor.
• Major surgery, other than local procedures, within 28 days prior to Cycle 1 Day 1,
without complete recovery.
• Spinal cord compression, leptomeningeal disease, or clinically active CNS metastases.
• Toxicity (excluding alopecia) from prior therapy that has not been completely resolved
to baseline at the time of consent.
• Active or prior documented autoimmune or inflammatory disorders within the past 5
years prior to Cycle 1 Day 1 (with exceptions).
• Active, uncontrolled bacterial, viral, or fungal infections requiring systemic
therapy.
• Inability to swallow, impairment of gastrointestinal (GI) function or GI disease that
may significantly alter the absorption of the trial drugs.
• Inadequate cardiac and/or vascular function, including receipt of treatment for
unstable angina, myocardial infarction, and/or cerebro-vascular attack within the
prior 6 months, mean QTcF ≥470 ms, or Class II or greater congestive heart failure.
• Other invasive malignancy within 2 years.
• Other protocol-defined exclusion criteria may apply.
Solid Tumors With HRAS Alterations, Non Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Clear Cell Renal Cell Carcinoma (ccRCC), Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
A Study of NDI 1150-101 in Patients With Solid Tumors
This study is to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose
(RP2D) and to investigate the safety, pharmacokinetics (PK), pharmacodynamics, and
preliminary antitumor activity of NDI-101150 given as monotherapy or in combination with
pembrolizumab in adult patients with advanced solid tumors.
Hamid Emamekhoo, M.D.
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT05128487
Show full eligibility criteria
Hide eligibility criteria
Key
Inclusion Criteria:
• Life expectancy of ≥ 12 weeks
• Measurable or non-measurable disease for Dose Escalation; measurable disease using
RECIST v1.1 is required for Dose Expansion
• Recovered from prior therapy to Grade ≤ 1 or return to baseline status (except for
alopecia)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patients with adequate bone marrow, kidney and liver function
• Last dose of previous anticancer therapy ≥ 4 weeks prior to first dose of NDI-101150;
includes prior anti-PD-1 or anti-PD-L1 therapy, other anticancer therapy,
radiotherapy, or surgical intervention
• For Dose Escalation Phase Only (Dose Escalation, Monotherapy and Combination Therapy):
Histologically or cytologically confirmed advanced or metastatic solid tumors for whom
no standard therapies are available or refractory to standard therapy
• For Dose Expansion Phase (Dose Expansion, Monotherapy and Combination Therapy):
Willing to consent to required tumor biopsy(ies). Histologically or cytologically
confirmed advanced or metastatic G/GEJ, NSCLC or RCC for which no standard therapy is
available or are refractory to standard therapy
Key
Exclusion Criteria:
• Previous solid organ or hematopoietic cell transplant
• Central nervous system (CNS) malignant disease not previously treated, active
leptomeningeal disease, uncontrolled symptomatic CNS involvement, or CNS malignant
disease requiring steroid or other therapeutic intervention
• Prior anticancer therapy within 2-6 weeks of trial start (depending on nature of
therapy).
• Clinically significant cardiovascular disease
• History of severe hypersensitivity reaction to treatment with monoclonal antibody(ies)
(for combination therapy cohorts only)
• History of interstitial lung disease, idiopathic pulmonary fibrosis, pneumonitis
(including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans,
cryptogenic organizing pneumonia, etc.), or evidence of history of pneumonitis on
chest computed tomography scan in the last 6 months
• Known additional malignancy that is active and/or in progression requiring treatment
• Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function,
unstable pulmonary condition, uncontrolled diabetes, thromboembolic event within the
past 3 months) or any important medical or psychiatric illness or abnormal laboratory
finding
• Unable to discontinue medications that are strong inducers or inhibitors of CYP3A4
and/or CYP2C8
• History of severe irAE that led to permanent discontinuation of prior immunotherapy
• History of recent Grade >/= 3 irAE or any Grade 4 life-threatening irAE, neurologic or
ocular AE of any grade while receiving prior immunotherapy
NOTE: Other protocol defined Inclusion and Exclusion criteria may apply.
Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Sarcoma, Uterus
Study of EO-3021 in Adult Patients With Solid Tumors Likely to Express CLDN18.2
This study is an open-label, international, multi-center, Phase 1 study in adult patients
with solid tumors likely to express CLDN18.2.
Nataliya Uboha, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05980416
Show full eligibility criteria
Hide eligibility criteria
Key
Inclusion Criteria:
• Availability of tumor tissue (archived and fresh tumor biopsy, if medically feasible)
• Select advanced or metastatic solid tumor that is likely to express CLDN18.2 such as
gastric/GEJ, pancreatic and esophageal cancer
• ≥ 18 years of age
• ECOG performance status (PS) 0 or 1 at Screening
• Progressed on or after standard therapy, or are intolerable for available standard
therapy, or there is no available standard therapy
• Have at least one measurable extra-cranial lesion as defined by RECIST v1.1
• Adequate organ function
• Life expectancy > 12 weeks
• Ability to understand the nature of this study, comply with protocol requirements, and
give written informed consent
• Willingness of men and women of reproductive potential to observe conventional and
effective birth control for the duration of treatment and for 3 months following study
completion
Key
Exclusion Criteria:
• Pregnant or breastfeeding
• Symptomatic or untreated brain metastases
• Have previously received CLDN18.2 antibody drug conjugates (ADCs) or any ADC
containing an auristatin payload (prior monoclonal antibody against CLDN18.2 may be
eligible)
• Have peripheral neuropathy Grade ≥2
• Have history of non-infectious pneumonitis/interstitial lung disease
• Have diagnosis of another malignancy, or history of systemic treatment for invasive
cancer within last 3 years. Note: Patients with Stage I cancer who have received
definitive local treatment and are considered unlikely to recur are eligible.
Diagnosis of non-melanoma skin cancer, carcinoma in situ of the cervix or breast, or
noninvasive tumor does not affect eligibility
• Have active ocular surface disease at baseline (based on screening ophthalmic
examination)
• Have serious concurrent illness or clinically relevant active bacterial, fungal or
viral infection
• Have previous hypersensitivity to any known components of EO-3021 or history of severe
infusion reaction or hypersensitivity (CTCAE Grade 3 or higher) with monoclonal
antibody treatment
• Clinically significant cardiac disease, including but not limited to symptomatic
congestive heart failure, unstable angina, acute myocardial infarction within 6 months
of planned first dose, or unstable cardiac arrhythmia requiring therapy (including
torsades de pointes)
• Have history of allogenic hematopoietic stem cell transplantation or solid organ
transplantation with ongoing systemic immunosuppressive therapy
• Patients who are not appropriate candidates for participation in this clinical study
for any other reason as deemed by the Investigator
Pancreas Neoplasm, Stomach Neoplasm, Gastrointestinal Neoplasms, Digestive System Neoplasm, Neoplasms by Site, Neoplasms, Lip, Oral Cavity and Pharynx, Esophagus, Colon, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Melanoma, Skin, Kaposi's Sarcoma, Breast, Cervix, Corpus Uteri, Other Female Genital, Other Male Genital, Kidney, Eye and Orbit, Brain and Nervous System, Other Endocrine System, Ill-Defined Sites, Anal, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Melanoma/Skin cancer, Ovary, Sarcoma, Uterus
A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors
The purpose of this study is to characterize the safety, tolerability, and efficacy of
IDE161.
Mark Burkard, MD, PhD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05787587
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Adult participants must be 18 years of age or older
2. Advanced or metastatic solid tumors excluding primary central nervous system (CNS)
tumors
3. Have documented evidence of genetic alterations conferring homologous recombination
deficiency
4. Participant must have progressed on at least one prior line of therapy in the advanced
or metastatic setting that is considered an appropriate standard of care, or for which
the participant has documented intolerance
Exclusion Criteria:
1. Known primary CNS malignancy
2. Impairment of GI function or GI disease that may significantly alter the absorption of
IDE161
3. Have active, uncontrolled infection
4. Clinically significant cardiac abnormalities
5. Major surgery within 4 weeks prior to enrollment
6. Radiation therapy within 2 weeks prior to enrollment
7. Systemic cytotoxic chemotherapy within 4 weeks prior to enrollment
8. Radioimmunotherapy within 6 weeks of enrollment
9. Treatment with a therapeutic antibody within 4 weeks prior to enrollment
10. Treatment with an anti-cancer small molecule within 5 half-lives (t1/2), or 2 weeks,
whichever is shorter
Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Thyroid, Other Endocrine System, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus, Advanced or Metastatic Solid Tumors, Breast Cancer, Ovarian Cancer, Pancreas Cancer, Prostate Cancer
This pilot comparative effectiveness trial will compare two active smoking cessation
treatments in terms of effectiveness, equity across patient subpopulations, and efficiency
among adult patients diagnosed with cancer within the past 3 years. An enhanced treatment
comprising 12 weeks of varenicline treatment and 7 smoking cessation coaching calls with a
cancer focus will be compared against an active comparator modeled after standard quitline
treatments (2 weeks of nicotine patch therapy with 3 phone coaching calls). Approximately 50
participants will be recruited to generate estimates of the effects, acceptability, costs,
and equity of enhanced treatment (vs. standard treatment), with the primary outcome being
abstinence from smoking 26 weeks after trying to quit.
Danielle Mccarthy
All
18 Years and over
Phase 4
This study is NOT accepting healthy volunteers
NCT06218823
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Alive (per medical record)
• Diagnosed with cancer in the past 3 years
• Received care from a participating oncology clinic in the past year
• Has a current tobacco use status
• Does not have a preferred language other than English (missing language preference
will be included).
• Valid address that is not a correctional facility or residential treatment/care
facility.
• No flag for patient cognitive impairment, activated health care power of attorney, or
other health care agent (e.g., legally authorized representative) in the EHR.
The following additional inclusion criteria must be met for inclusion in the CET
• Smoked combustible cigarettes in the past month.
• Able to speak and understand English.
• Willing to set a date to quit smoking in the next 60 days.
• Willing to receive smoking treatment information.
• Willing to complete study activities.
Exclusion Criteria:
• No current suicidal ideation.
• Suicide attempt in the past year.
• Currently receiving treatment for bipolar disorder, schizophrenia, schizoaffective
disorder, or psychotic disorder.
• Incarceration.
• Unable to provide informed consent to treatment (i.e., cannot answer questions about
study procedures or risks after hearing about the study).
Smoking Cessation, Cancer, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Mycosis Fungoides, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma, Multiple Myeloma, Lymphoid Leukemia, Myeloid and Monocytic Leukemia, Leukemia, other, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Any Site, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Leukemia, Lymphoma, Melanoma/Skin cancer, Sarcoma, Uterus
A Phase 1/2 Study of DCC-3116 in Patients With MAPK Pathway Mutant Solid Tumors
This is a Phase 1/2, multicenter, open label, first in human (FIH) study of DCC-3116 as
monotherapy, and in combination with trametinib, binimetinib, or sotorasib in patients with
advanced or metastatic solid tumors with RAS/MAPK pathway mutation. The study consists of 2
parts, a dose-escalation phase, and an expansion phase.
Nataliya Uboha, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04892017
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
1. Male or female participants ≥18 years of age
2. Dose Escalation Phase (Part 1):
1. Participants must have a pathologically confirmed diagnosis of an advanced or
metastatic solid tumor with a documented RAS, NF1, or RAF mutations. A molecular
pathology report documenting mutational status of RAS, NF1, or RAF must be
available.
2. Progressed despite standard therapies, and received at least 1 prior line of
anticancer therapy.
• Participants with a documented mutation in BRAF V600E or V600K must have
received approved treatments known to provide clinical benefit prior to
study entry.
3. Participants enrolled in the DCC-3116 and sotorasib cohort (Cohort D) must have a
KRAS G12C mutation.
3. Dose Expansion Phase (Part 2):
1. Cohort 1: Patients with Pancreatic Ductal Adenocarcinoma (PDAC).
• Pathologically confirmed PDAC with a documented mutation in KRAS.
• Received only 1 prior line of systemic therapy in the advanced or metastatic
setting.
2. Cohort 2: Patients with Non-Small Cell Lung Cancer (NSCLC)
• Pathologically confirmed NSCLC with a documented mutation in KRAS, NRAS,
NF1, or BRAF.
• Received at least 2 prior lines but no more than 4 prior lines of systemic
therapy in the advanced or metastatic setting.
3. Cohort 3: Patients with Colorectal Cancer (CRC)
• Pathologically confirmed CRC with a documented mutation in KRAS, NRAS, NF1,
or BRAF.
• Received at least 2 prior lines of systemic therapy in the advanced or
metastatic setting.
4. Cohort 4: Patients with Melanoma
• Pathologically confirmed melanoma with a documented mutation in NRAS.
• Received at least 1 but not more than 2 prior lines of systemic therapy in
the advanced or metastatic setting that included T-cell checkpoint
inhibitor-based therapy.
• Have not received prior MEK inhibitor therapy.
5. Cohort 5: Patients with KRAS G12C mutant NSCLC
• Pathologically confirmed NSCLC with a documented mutation in KRAS G12C.
• Received at least 1 prior line but no more than 3 prior lines of systemic
therapy in the advanced or metastatic setting.
• Have not received prior sotorasib or other KRAS G12C inhibitor therapy.
4. Must provide a fresh tumor biopsy from a primary or metastatic cancer lesion that can
be biopsied with acceptable risk as determined by the Investigator, and an archival
tumor tissue sample, if available. If a fresh tumor biopsy is not possible, then an
archival tumor tissue sample must be provided.
5. Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 (Dose Escalation) or 0 to 1
(Dose Expansion) at Screening
6. Adequate organ function and bone marrow function.
7. If a female of childbearing potential must have a negative pregnancy test prior to
enrollment and agree to follow the contraception requirements.
8. Male participants must agree to follow contraception requirements.
9. Must provide signed consent to participate in the study and is willing to comply with
study-specific procedures.
Exclusion Criteria:
1. Must not have received the following within the specified time periods prior to the
first dose of study drug:
1. Prior therapies (anticancer or therapies given for other reasons) that are known
strong or moderate inhibitors or inducers of CYP3A4 or P-gp including certain
herbal medications (eg, St. John's Wort): 14 days or 5× the half-life of the
medication (whichever is longer)
2. All other prior anticancer therapies or any therapy that is investigational for
the participant's condition with a known safety and PK profile: 14 days or 5× the
half-life of the medication (whichever is shorter)
3. Investigational therapies with unknown safety and PK profile: 28 days. If there
is enough data on the investigational therapy to assess the risk for drug.-drug
interactions and late toxicities of prior therapy as low, the Sponsor's Medical
Monitor may approve a shorter washout of 14 days
4. Grapefruit or grapefruit juice: 14 days
2. Have not recovered from all toxicities from prior therapy according to National Cancer
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
3. Presence or history of central nervous system (CNS) metastases or leptomeningeal
disease, with some exceptions
4. New York Heart Association Class III or IV heart disease, active ischemia, or any
other uncontrolled cardiac condition such as angina pectoris, clinically significant
cardiac arrhythmia requiring therapy, uncontrolled hypertension, congestive heart
failure, or myocardial infarction within 6 months prior to the first dose of study
drug.
5. Prolongation of the QT interval corrected by Fridericia's formula (QTcF) based on
repeated demonstration of QTcF >450 ms in males or >470 ms in females at screening, or
history of long QT syndrome.
6. Left ventricular ejection fraction (LVEF) <50% at Screening
7. Systemic arterial thrombotic or embolic events
8. Systemic venous thrombotic events
9. Malabsorption syndrome
10. Bone disease that requires ongoing treatment or has required treatment.
11. Major surgery within 4 weeks of the first dose of study drug. All surgical wounds must
be healed and free of infection or dehiscence before the first dose of the study drug.
12. Any other clinically significant comorbidities.
13. For participants receiving DCC-3116 and trametinib combination or DCC-3116 and
binimetinib combination: previous treatment with trametinib or binimetinib that
resulted in treatment discontinuation due to intolerability as a result of an adverse
event (AE) that was considered related to trametinib or binimetinib.
14. For participants receiving DCC-3116 and sotorasib combination in Dose Escalation Part
1: previous treatment with sotorasib that resulted in treatment discontinuation due to
intolerability as a result of an adverse event (AE) that was considered related to
sotorasib.
15. For participants receiving DCC-3116 and sotorasib combination: Use of proton pump
inhibitors (PPIs) and H2 receptor antagonists that cannot be discontinued 3 days prior
to the start of study drug administration.
16. Known allergy or hypersensitivity to any component of the investigational drug
products.
17. Known human immunodeficiency virus unless the following requirements are met:
1. CD4 count >350/µL
2. No AIDS-defining opportunistic infection in the last 12 months
3. Stable anti-retroviral regimen with medications that are not prohibited by the
protocol for at least 4 weeks with HIV viral load less than 400 copies/mL prior
to enrollment.
18. Known active hepatitis B, active hepatitis C infection or if the participant is taking
medications that are prohibited per protocol.
19. If female, the participant is pregnant or lactating.
20. Ongoing participation in an interventional study.
21. For participants receiving DCC-3116 and binimetinib combination: Known Gilbert's
syndrome
Pancreatic Ductal Adenocarcinoma, Non-Small Cell Lung Cancer, Colorectal Cancer, Melanoma, Advanced Solid Tumor, Metastatic Solid Tumor, Lip, Oral Cavity and Pharynx, Esophagus, Stomach, Small Intestine, Colon, Rectum, Anus, Liver, Pancreas, Other Digestive Organ, Larynx, Lung, Other Respiratory and Intrathoracic Organs, Bones and Joints, Soft Tissue, Melanoma, Skin, Kaposi's Sarcoma, Other Skin, Breast, Cervix, Corpus Uteri, Ovary, Other Female Genital, Prostate, Other Male Genital, Urinary Bladder, Kidney, Other Urinary, Eye and Orbit, Brain and Nervous System, Thyroid, Other Endocrine System, Other Hematopoietic, Unknown Sites, Ill-Defined Sites, Anal, Bladder, Brain/Central Nervous System, Colon and Rectum, Endocrine cancers, Gastrointestinal cancers, other, Genitourinary cancers, other, Head and Neck, Hematologic cancers, other, Melanoma/Skin cancer, Sarcoma, Uterus
Testing the Combination of New Anti-cancer Drug Peposertib With Avelumab and Radiation Therapy for Advanced/Metastatic Solid Tumors and Hepatobiliary Malignancies
This phase I/II trial studies the best dose and side effects of peposertib and to see how
well it works with avelumab and hypofractionated radiation therapy in treating patients with
solid tumors and hepatobiliary malignancies that have spread to other places in the body
(advanced/metastatic). Peposertib may stop the growth of tumor cells by blocking some of the
enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab,
may help the body's immune system attack the cancer, and may interfere with the ability of
tumor cells to grow and spread. Hypofractionated radiation therapy delivers higher doses of
radiation therapy over a shorter period of time and may kill more tumor cells and have fewer
side effects. Giving peposertib in combination with avelumab and hypofractionated radiation
therapy may work better than other standard chemotherapy, hormonal, targeted, or
immunotherapy medicines available in treating patients with solid tumors and hepatobiliary
malignancies.
Jeremy Kratz, MD
All
18 Years and over
Phase 1/Phase 2
This study is NOT accepting healthy volunteers
NCT04068194
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• PHASE 1: Patients must have a histologically confirmed metastatic or locally advanced
unresectable solid tumor that has progressed on or after available standard of care
therapy or for which no acceptable standard of care therapy exists, or in which the
patient declines standard of care therapy (each patient that declines standard of care
therapy will be documented in the case report form)
• PHASE 2: Patients must have a histologically confirmed metastatic or locally advanced
unresectable cholangiocarcinoma/gallbladder carcinoma that has progressed on at least
1 prior standard of care therapy or for which no acceptable standard of care therapy
exists, or in which the patient declines standard of care therapy (each patient that
declines standard of care therapy will be documented in the case report form)
• Age >= 18 years
• Because no dosing or adverse event data are currently available on the use of
M3814 in combination with avelumab in patients < 18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Patients with at least 1 index lesion to irradiate for whom palliative radiation
treatment is indicated (including but not limited to pain and/or symptom control,
prevention of disease -related complications, and preservation of organ function).
Lung and liver lesions are preferred, though alternate lesions may be considered after
discussion with trial principal investigator (PI). Up to 2 lesions may be considered
for irradiation provided at least 1 lesion will receive the study treatment of total
of 60 Gy and all prescribed irradiation will be completed within the radiation window
• Patients with at least 1 Response Evaluation Criteria in Solid Tumors (RECIST)
measurable lesion (to be unirradiated) (defined as those accurately measured in at
least one dimension, with the longest diameter to be recorded for non-nodal lesions
and the shortest diameter for nodal lesions). Measurable is defined as at least 10 mm
in longest diameter for solid tumors, at least 15 mm in shortest diameter for lymph
nodes
• Patients must be willing to undergo fresh biopsies at baseline (as opposed to using
archival tissue), in the event their baseline tissue was obtained > 12 months prior to
study consent and/or they are randomized to the gamma H2AX pNBS1 multiplex IFA assay
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelet count >= 100,000/mcL
• Hemoglobin >= 9.0 g/dL
• Serum creatinine =< 1.5 x upper limit of normal (ULN) OR calculated serum creatinine
clearance (glomerular filtration rate [GFR] can be used in place of creatinine or
creatinine clearance) >= 60 mL/min for participants with creatinine levels > 1.5 x
institutional ULN
• Calculate serum creatinine clearance using the standard Cockcroft-Gault formula
• Serum total bilirubin =< 1.5 x ULN or direct bilirubin =< ULN for participants with
total bilirubin > 1.5 x ULN
• Patients with known Gilbert disease with serum bilirubin level =< 3 x ULN are
eligible
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x
ULN or =< 5.0 x ULN for patients with hepatobiliary tumors/liver metastases
• Albumin >= 2.8 g/L
• International normalized ratio (INR) or prothrombin time (PT) or activated partial
thromboplastin time (aPTT) =< 1.5 x ULN
• This applies only to patients not receiving therapeutic anticoagulation; patients
receiving therapeutic anticoagulation should be on a stable dose
• Participants must have the ability to swallow and retain oral medication and not have
any clinically significant gastrointestinal abnormalities that might alter absorption
• Female patients of childbearing potential must have a negative urine or serum
pregnancy test within 72 hours prior to receiving the first dose of study medication.
If the urine test is positive or cannot be confirmed as negative, a serum pregnancy
test will be required. The effects of M3814 and avelumab on the developing human fetus
are unknown and there is the potential for teratogenic or abortifacient effects. For
this reason, women and men of child-bearing potential must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to study
entry, for the duration of study treatment, and for 6 months after completion of M3814
and avelumab administration. Should a woman become pregnant or suspect she is pregnant
while she or her partner is participating in this study, she should inform her
treating physician immediately. Because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with M3814 and
avelumab, breastfeeding should be discontinued if the mother is treated with M3814 and
avelumab
• Ability to understand and the willingness to sign a written informed consent document.
Participants with impaired decision-making capacity (IDMC) who have a close caregiver
or legally authorized representative (LAR) and/or family member available will also be
eligible
Exclusion Criteria:
• PHASE I: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other
immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents
• PHASE II: Patients who have received prior anti-CTLA-4, anti-PD-1, anti-PD-L1 or other
immune checkpoint inhibitor therapeutic antibodies or pathway-targeting agents with
the following exceptions:
• Patients who have only received previous durvalumab (anti-PD-L1) in combination
with gemcitabine +/- cisplatin as part of first line therapy (TOPAZ-1 regimen)
are eligible
• Patients who have only received previous pembrolizumab (anti-PD-1) in combination
with gemcitabine +/- cisplatin as part of first line therapy (KEYNOTE-966
regimen) are eligible
• Patients who have had chemotherapy, definitive radiation, biological cancer therapy,
or investigational agent/device within 21 days of first planned dose of study therapy
(within 14 days for palliative radiation). Previously irradiated lesions may be
re-irradiated provided there is disease progression in the irradiated lesion and the
prescribed radiation dosage can safely be re- administered
• Patients who have not recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > Common Terminology Criteria for Adverse Events
[CTCAE] grade 1) with the exception of alopecia
• Patients with untreated/uncontrolled central nervous system (CNS)/leptomeningeal
disease. Patients with asymptomatic, treated CNS disease are eligible if the treating
physician determines that immediate CNS specific treatment is not required and is
unlikely to be required during the first cycle of therapy and the following criteria
are met:
• Radiographic demonstration of clinical stability upon the completion of
CNS-directed therapy and no evidence of interim progression between the
completion of CNS-directed therapy and the screening radiographic study done >= 4
weeks from completion of radiotherapy and >= 2 weeks from discontinuation of
corticosteroids
• No stereotactic radiation or whole-brain radiation within 28 days prior to
randomization
• Patients with active autoimmune disease requiring systemic corticosteroids greater
than the equivalent of prednisone 10 mg daily including but not limited to: systemic
lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, colitis,
vascular thrombosis associated with antiphospholipid syndrome, Wegener's
granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple
sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis, with the
following exceptions:
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone are eligible
• Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are
eligible
• Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with
dermatologic manifestations only who require only low potency topical steroids
(e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%,
desonide 0.05%, alclometasone dipropionate 0.05%) are eligible
• Patients receiving treatment with systemic immunosuppressive medications (including,
but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate,
thalidomide, and anti-tumor necrosis factor [TNF] agents) within 6 weeks must
discontinue these medications prior to starting M3814 and avelumab on day 7, with the
exception of:
• Patients with active autoimmune disease managed with systemic corticosteroids
less than the equivalent of prednisone 10 mg daily
• Patients who have received acute, low dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea)
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone)
for patients with orthostatic hypotension and adrenocortical insufficiency
• Patients who have undergone prior solid organ or bone marrow transplant with the
exception of patients with prior renal transplant for whom dialysis may be employed in
the event of graft rejection
• Patients with uncontrolled intercurrent illness (e.g., including but not limited to
uncontrolled hypertension [HTN] [systolic blood pressure (BP) > 150, diastolic BP >
100], symptomatic congestive heart failure [CHF], unstable angina pectoris, ischemic
myocardial infarction [MI] within 6 months, cardiac arrhythmia, recent transient
ischemic attack [TIA or cerebrovascular accident (CVA)]) within 6 months
• Patients with serious active infection (e.g. requiring hospitalization and/or
intravenous [IV] antibiotics) within 4 weeks prior to starting M3814 and avelumab, or
signs/symptoms of infection or receiving oral or IV antibiotics for the treatment of
active systemic infection within 2 weeks prior to starting M3814 and avelumab.
Patients receiving prophylactic antibiotics are eligible
• Patients with known chronic hepatitis B virus (HBV) infection must have an
undetectable viral load on suppressive therapy if indicated. Patients with known
chronic hepatitis C (HCV) infection must have been treated and cured. Patients who are
currently on curative treatment are eligible if they have an undetectable HCV viral
load
• Patients with known human immunodeficiency virus (HIV) are allowed on study provided
they have:
• A stable regimen of highly active anti-retroviral therapy (HAART)
• No requirement for concurrent antibiotics or antifungal agents for the prevention
of opportunistic infection
• A CD4 count above 250 cells/mcL
• An undetectable HIV viral load on standard polymerase chain reaction (PCR)-based
testing
• Patients with history of idiopathic pulmonary fibrosis, pneumonitis (including drug
induced), organizing pneumonia (e.g., bronchiolitis obliterans, cryptogenic organizing
pneumonia), or evidence of active pneumonitis on screening chest computed tomography
(CT) scan
• Patients with known concurrent malignancy that is expected to require active treatment
within two years, or may interfere with the interpretation of the efficacy and safety
outcomes of this study in the opinion of the treating investigator. Superficial
bladder cancer, nonmelanoma skin cancers, and low-grade prostate cancer not requiring
cytotoxic therapy should not exclude participation in this trial. Patients with
chronic lymphocytic leukemia (CLL) may be enrolled if they do not require active
chemotherapy and their hematologic, renal and hepatic function meets criteria
previously mentioned
• Patients with psychiatric illness/social situations that would limit compliance with
study requirements
• History of allergic reactions attributed to compounds of similar chemical or biologic
composition to M3814 or avelumab
• Patients unable to discontinue medications or substances that are potent inhibitors,
inducers or sensitive substrates of CYP3A4/5 or CYP2C19 prior to starting M3814 and
avelumab are ineligible. Medications or substances that are strong inhibitors of
CYP3A4/5 or CYP2C19 must be discontinued at least 1 week prior to first M3814 dose.
Strong inducers of CYP3A4/5 or CYP2C19 must be stopped at least 3 weeks prior to the
first dose. Drugs mainly metabolized by CYP3A with a narrow therapeutic index as
judged by the investigator must stop at least 1 day prior to first M3814 dose. Because
the lists of these agents are constantly changing, it is important to regularly
consult a frequently-updated medical reference. 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. The primary
elimination mechanism of avelumab is proteolytic degradation, thus there are no
contraindicated medications with respect to avelumab
• Patients who cannot discontinue concomitant proton-pump inhibitors (PPIs) prior to
starting M3814 and avelumab. These must be discontinued >= 5 days prior to starting
M3814 and avelumab. Patients do not need to discontinue calcium carbonate. H2 blockers
are allowed provided they are taken at least 2 hours after M3814 dose
• Patients receiving sorivudine or any chemically related analogues (such as brivudine)
and not able to discontinue prior to starting M3814 and avelumab are excluded
• Pregnant and lactating women are excluded from this study because M3814 and avelumab
are agents 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 M3814 and avelumab, breastfeeding should be discontinued
if the mother is treated with M3814 and avelumab
• Patients who have received live vaccination within 30 days before starting M3814 and
avelumab
Cholangiocarcinoma, Gallbladder Carcinoma, Stage III Gallbladder Cancer AJCC v8, Stage III Hilar Cholangiocarcinoma AJCC v8, Stage III Intrahepatic Cholangiocarcinoma AJCC v8, Stage IV Gallbladder Cancer AJCC v8, Stage IV Hilar Cholangiocarcinoma AJCC v8, Stage IV Intrahepatic Cholangiocarcinoma AJCC v8, Liver, Other Digestive Organ, Gastrointestinal cancers, other
A Study Evaluating Atezolizumab and Bevacizumab, With or Without Tiragolumab, in Participants With Untreated Locally Advanced or Metastatic Hepatocellular Carcinoma (IMbrave152) (SKYSCRAPER-14)
The purpose of this study is to assess the efficacy and safety of tiragolumab, an anti-TIGIT
monoclonal antibody, when administered in combination with atezolizumab and bevacizumab as
first-line treatment, in participants with unresectable, locally advanced or metastatic
hepatocellular carcinoma (HCC).
Jeremy Kratz, MD
All
18 Years and over
Phase 3
This study is NOT accepting healthy volunteers
NCT05904886
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by
histology/cytology or clinically by American Association for the Study of Liver
Diseases (AASLD) criteria in cirrhotic participants
• Disease that is not amenable to curative surgical and/or locoregional therapies
• No prior systemic treatment for locally advanced or metastatic and/or unresectable HCC
• Measurable disease according to RECIST v1.1
• ECOG Performance Status of 0 or 1 within 7 days prior to randomization
• Child-Pugh Class A within 7 days prior to randomization
• Adequate hematologic and end-organ function
• Female participants of childbearing potential must be willing to avoid pregnancy
within 5 months after the final dose of atezolizumab, within 6 months after the final
dose of bevacizumab, and within 90 days after the final dose of tiragolumab/placebo
• Male participants with a female partner of childbearing potential or pregnant female
partner must remain abstinent or use a condom during the treatment period and for 6
months after the final dose of bevacizumab and for 90 days after the final dose of
tiragolumab/placebo to avoid exposing the embryo.
Exclusion Criteria:
• Pregnancy or breastfeeding within 5 months after the final dose of atezolizumab,
within 6 months after the final dose of bevacizumab, and within 90 days after the
final dose of tiragolumab/placebo
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies
• Treatment with investigational therapy within 28 days prior to initiation of study
treatment
• Treatment with locoregional therapy to liver within 28 days prior to initiation of
study treatment, or non-recovery from side effects of any such procedure
• Treatment with systemic immunostimulatory agents
• Treatment with systemic immunosuppressive medication
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or
that are at high risk for bleeding
• A prior bleeding event due to esophageal and/or gastric varices within 6 months prior
to initiation of study treatment
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest computed tomography (CT) scan
• History of malignancy other than HCC within 5 years prior to screening, with the
exception of malignancies with a negligible risk of metastasis or death
• Mixed histology or other subtypes/variants of HCC, including, but not limited to,
known liver adenocarcinoma, fibrolamellar HCC, sarcomatoid HCC, other rare HCC
variant, or mixed cholangiocarcinoma and HCC
• Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV)
• Acute Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV
infection
• Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases.
SynKIR-110 for Mesothelin Expressing Ovarian Cancer, Cholangiocarcinoma or Mesothelioma
This first-in-human (FIH) trial is designed to assess the safety, feasibility, and potential
activity of a single intravenous (IV) dose of SynKIR-110 administered to subjects with
mesothelin-expressing advanced ovarian cancer, mesothelioma, and cholangiocarcinoma.
Zhubin Gahvari, MD
All
18 Years and over
Phase 1
This study is NOT accepting healthy volunteers
NCT05568680
Show full eligibility criteria
Hide eligibility criteria
Inclusion Criteria:
• Pathologically confirmed recurrent or relapsed advanced ovarian cancer, primary
peritoneal cancer, fallopian tube cancer, cholangiocarcinoma, or epithelial
mesothelioma (pleural or peritoneal) after at least 1 prior line of systemic therapy
for advanced disease
• Adult 18 years of age or older.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• For ovarian cancer and mesothelioma, tumor expression of mesothelin ≥50% of tumor
cells with ≥2+ staining intensity (on a scale of 0 to 3). For cholangiocarcinoma ≥10%
of cells at any staining intensity (≥1+).
• Has at least 1 measurable lesion by iRECIST for ovarian cancer or cholangiocarcinoma
or lesions measurable for mRECIST for mesothelioma.
• Satisfactory Blood coagulation parameters:
• Satisfactory organ and bone marrow function
Exclusion Criteria:
• Active invasive cancers other than mesothelioma, cholangiocarcinoma, and ovarian
unless surgically and medically cured without evidence of recurrent disease for 5
years.
• History of T or B cell malignancies or previous gene-engineered T cell therapies.
• Sarcomatoid/biphasic mesothelioma.
• Pulmonary exclusions:
• Have acquired hereditary, congenital immunodeficiency or have recognized
immunodeficiency disease
• Active hepatitis B, active hepatitis C, or any HIV infection at the time of screening
• Active autoimmune disease
Ovarian Cancer, Cholangiocarcinoma Recurrent, Mesothelioma, Malignant, Small Intestine, Liver, Other Digestive Organ, Lung, Other Respiratory and Intrathoracic Organs, Ovary, Other Female Genital, Gastrointestinal cancers, other
*Note: Email is generally not a secure way to communicate sensitive or health-related information as there are many ways for unauthorized users to access email. You should avoid sending sensitive, detailed personal information by email.