A Phase 2, Multicenter, Multi Arm, Study to Evaluate MK-1308A (Co-formulated Quavonlimab (MK-1308)/Pembrolizumab) Versus Other Treatments in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Cancer: (MK-1308A-008)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 302
- 试验地点
- 109
- 主要终点
- Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of co-formulated pembrolizumab/quavonlimab versus other treatments in participants with MSI-H or dMMR Metastatic Stage IV Colorectal Cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a histologically confirmed diagnosis of Stage IV CRC adenocarcinoma (as defined by American Joint Committee on Cancer [AJCC] version 8)
- •Has locally confirmed dMMR/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
- •- 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.
- •- Has untreated Stage IV dMMR/MSI-H CRC with no prior chemotherapy or immunotherapy for this disease
排除标准
- •Has received prior therapy with an agent directed to another stimulatory or coinhibitory T-cell receptor
- •Has received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
- •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
- •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 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
研究组 & 干预措施
Pembrolizumab
Participants receive pembrolizumab 400 mg intravenously (IV) every 6 weeks (Q6W) for up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Pembrolizumab/Quavonlimab
Participants receive co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) Q6W for up to approximately 2 years.
干预措施: Pembrolizumab/Quavonlimab (Biological)
Pembrolizumab/Vibostolimab
Participants receive co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) Q3W for up to approximately 2 years.
干预措施: Pembrolizumab/Vibostolimab (Biological)
Pembrolizumab Plus MK-4830
Participants receive pembrolizumab 200 mg plus MK-4830 800 mg Q3W for up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Pembrolizumab Plus MK-4830
Participants receive pembrolizumab 200 mg plus MK-4830 800 mg Q3W for up to approximately 2 years.
干预措施: MK-4830 (Biological)
Cohort B - Pembrolizumab/Favezelimab
Participants receive co-formulated pembrolizumab/favezelimab (200 mg/800 mg) every 3 weeks (Q3W) for up to approximately 2 years.
干预措施: Pembrolizumab/Favezelimab (Biological)
Cohort B - Pembrolizumab Plus MK-4830
Participants receive pembrolizumab 200 mg plus MK-4830 800 mg Q3W for up to approximately 2 years.
干预措施: MK-4830 (Biological)
Cohort B - Pembrolizumab/Vibostolimab
Participants receive co-formulated pembrolizumab/vibostolimab (200 mg/200 mg) Q3W for up to approximately 2 years.
干预措施: Pembrolizumab/Vibostolimab (Biological)
Cohort A - Pembrolizumab
Participants in Cohort A receive pembrolizumab 400 mg intravenously (IV) Q6W for up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Cohort A - Pembrolizumab/Quavonlimab
Participants in Cohort A receive co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) every 6 weeks (Q6W) for up to approximately 2 years.
干预措施: Pembrolizumab/Quavonlimab (Biological)
Cohort B - Pembrolizumab/Quavonlimab
Participants received co-formulated pembrolizumab/quavonlimab (400 mg/25 mg) Q6W for up to approximately 2 years.
干预措施: Pembrolizumab/Quavonlimab (Biological)
Cohort B - Pembrolizumab Plus MK-4830
Participants receive pembrolizumab 200 mg plus MK-4830 800 mg Q3W for up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
Cohort B - Pembrolizumab
Participants in Cohort B receive pembrolizumab 400 mg IV Q6W for up to approximately 2 years.
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR)
时间窗: Up to approximately 46 months
ORR is defined as the percentage of participants who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR as assessed by BICR will be presented.
次要结局
- Overall Survival (OS)(Up to approximately 46 months)
- ORR per RECIST 1.1 as assessed by Investigator(Up to approximately 46 months)
- Duration of Response (DOR) per RECIST 1.1 as assessed by BICR(Up to approximately 46 months)
- Progression-Free Survival (PFS) per RECIST 1.1 as assessed by BICR(Up to approximately 46 months)
- PFS per RECIST 1.1 as assessed by Investigator(Up to approximately 46 months)
- DOR per RECIST 1.1 as assessed by Investigator(Up to approximately 46 months)
- Number of Participants Who Experienced an Adverse Event (AE)(Up to approximately 60 months)
- Number of Participants Discontinuing Study Treatment Due to an AE(Up to approximately 60 months)