Study of Pembrolizumab (MK-3475) vs Standard Therapy in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (MK-3475-177/KEYNOTE-177)
Condition: Colorectal Carcinoma
MeSH terms: Carcinoma; Colorectal Neoplasms; Microsatellite Instability
Intervention: mFOLFOX6; FOLFIRI; pembrolizumab; bevacizumab; cetuximab
Intervention description: Regimen consists of oxaliplatin 85 mg/m^2 IV on Day 1, leucovorin 400 mg/m^2 or levoleucovorin 200 mg/m^2 IV on Day 1, 5-fluorouracil (5-FU) 400 mg/m^2 IV bolus on Day 1 and then 1200 mg/m^2/day IV over 2 days for total dose of 2400 mg/m^2 in each 2-week cycle; Regimen consists of irinotecan 180 mg/m^2 IV on Day 1, leucovorin 400 mg/m^2 or levoleucovorin 200 mg/m^2 IV on Day 1, 5-FU 400 mg/m^2 IV bolus on Day 1 and then 1200 mg/m^2/day IV over 2 days for total dose of 2400 mg/m^2 in each 2-week cycle; MK-3475 SCH 900475 KEYTRUDA®
Intervention MeSH terms: Bevacizumab; Pembrolizumab; Cetuximab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 307.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1, PDL1)

Summary:

      In this study, participants with stage IV Microsatellite Instability-High (MSI-H) or Mismatch
      Repair Deficient (dMMR) colorectal carcinoma (CRC) will be randomly assigned to receive
      either pembrolizumab or the Investigator's choice of 1 of 6 standard of care (SOC)
      chemotherapy regimens for the treatment of advanced colorectal carcinoma. The primary study
      hypothesis is that pembrolizumab will prolong progression-free survival (PFS) or overall
      survival (OS) compared to current SOC chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Locally confirmed dMMR or MSI-H stage IV colorectal carcinoma

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days
             prior to study start

          -  Life expectancy of at least 3 months

          -  Measurable disease

          -  Female participants of childbearing potential must be willing to use adequate
             contraception for the course of the study starting with the first dose of study
             medication through 180 days after the last dose of standard of care (SOC) therapy or
             120 days after the last pembrolizumab dose

          -  Male participants must agree to use adequate contraception for the course of the study
             starting with the first dose of study medication through 180 days after the last dose
             of study medication for chemotherapy arm (no contraception requirement for
             pembrolizumab [MK-3475] arm)

          -  Adequate organ function

        Exclusion Criteria:

          -  Has received prior systemic therapy for Stage IV colorectal cancer. May have received
             prior adjuvant chemotherapy for colorectal cancer as long as it was completed at least
             6 months prior to randomization on this study

          -  Currently participating and receiving treatment in another study, or participated in a
             study of an investigational agent and received treatment, or used an investigational
             device within 4 weeks of randomization

          -  Active autoimmune disease that has required systemic treatment in past 2 years

          -  Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
             of immunosuppressive therapy within 7 days prior to randomization on this study

          -  Radiation therapy within 4 weeks prior to randomization on this study and not
             recovered to baseline from adverse events due to radiation therapy

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  Major surgical procedure, open biopsy or significant traumatic injury within 28 days
             prior to randomization on this study

          -  Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-programmed
             cell death [PD]-1, anti-PD ligand 1 [L1], anti-PD-L2 agent, or anti-cytotoxic
             T-lymphocyte-associated protein 4 [CTLA-4] agent, etc.)

          -  Another malignancy that is progressing or requires active treatment with the exception
             of non-melanomatous skin cancer that has undergone potentially curative therapy and in
             situ cervical carcinoma

          -  Received a live or a live attenuated vaccine within 30 days of planned start of study
             medication

          -  Known history of Human Immunodeficiency Virus (HIV), Hepatitis B or C

          -  Known history of, or any evidence of interstitial lung disease or active,
             non-infectious pneumonitis

          -  Known history of active tuberculosis (Bacillus tuberculosis [TB])

          -  Active infection requiring systemic therapy

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the study

          -  Pregnant, breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 180 days
             after the last dose of SOC (for male and female participants) or 120 days after the
             last dose of pembrolizumab (for female participants only)