A Multi Arm Study in Participants with MSI-High Metastatic Colorectal Cancer
- Conditions
- Participants with Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal CancerMedDRA version: 20.1Level: LLTClassification code: 10079619Term: MSI-high Class: 10029104MedDRA version: 21.0Level: PTClassification code: 10010035Term: Colorectal cancer stage IV Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2022-502100-70-00
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 387
Has a histologically confirmed diagnosis of Stage IV Colorectal Cancer (CRC) adenocarcinoma (as defined by American Joint Committee on Cancer [AJCC] version 8), Has locally confirmed Mismatch Repair Deficient (dMMR) /Microsatellite Instability-High (MSI-H), Has a life expectancy of at least 3 months, Female participants are eligible to participate if not pregnant or breastfeeding, and not a woman of childbearing potential (WOCBP), or if a WOCBP then uses a contraceptive method that is highly effective or is abstinent on a long-term and persistent basis, during the intervention period and for at least 120 days after the last dose of study intervention, Has measurable disease per RECIST 1.1 as assessed by the site and verified by BICR, Submit an archival (within 5 years of Screening) or newly obtained tumor tissue sample that has not been previously irradiated; formalin-fixed, paraffin embedded (FFPE) blocks are preferred to slides, Has adequate organ function, Cohort A: Has been previously treated for their Stage IV dMMR/MSI-H CRC and radiographically progressed on or after or could not tolerate standard treatment, which must include all of the following agents if approved and locally available in the country where the participant is randomized: •Fluoropyrimidine, irinotecan and oxaliplatin (capecitabine is acceptable as equivalent to fluorouracil in prior therapy) •With or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (e.g., bevacizumab) •At least one of the anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) for rat sarcoma viral oncogene homolog (RAS) wild-type participants with left-sided tumors. Prior EGFR therapy is optional for patients with right sided RAS Wild-type (WT) tumors., Cohort B: • Has untreated Stage IV dMMR/MSI-H CRC with no prior chemotherapy or immunotherapy for this disease
Has received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor, Has severe hypersensitivity (=Grade 3) to pembrolizumab, quavonlimab, favezelimab, vibostolimab, MK-4830, and/or any of their excipients, Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs), Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis, Has a history of acute or chronic pancreatitis, Has neuromuscular disorders associated with an elevated creatine kinase, Has urine protein =1 gram/24 hours, Has an active infection requiring systemic therapy (e.g., tuberculosis, known viral or bacterial infections, etc.), Has a known history of Human Immunodeficiency Virus (HIV) infection, Concurrent active Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] positive and/or detectable Hepatitis B Virus [HBV] deoxyribonucleic acid [DNA]) and Hepatitis C virus (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid [RNA] infection, Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study intervention administration, or New York Heart Association Class III or IV congestive heart failure. Medically controlled arrhythmia stable on medication is permitted, Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention, Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks before randomization/allocation, Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator, Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study, Has had an allogenic tissue/solid organ transplant, Has not recovered adequately from a surgery procedure, and/or has any complications from a prior surgery before starting study intervention, Has received prior radiotherapy within 2 weeks of start of study intervention, Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention, Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention, Has a 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 medication, Has a known additional malignancy that is progressing or has required active treatment within the past 2 years, Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method