Clinical Trials /

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)

NCT02563002

Description:

In this study, participants with MSI-H or dMMR advanced colorectal carcinoma 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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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)
  • Official Title: A Phase III Study of Pembrolizumab (MK-3475) vs. Chemotherapy in Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (KEYNOTE-177)

Clinical Trial IDs

  • ORG STUDY ID: 3475-177
  • SECONDARY ID: 2015-002024-89
  • SECONDARY ID: 163238
  • NCT ID: NCT02563002

Conditions

  • Colorectal Carcinoma

Interventions

DrugSynonymsArms
mFOLFOX6Standard of Care
FOLFIRIStandard of Care
pembrolizumabPembrolizumab
bevacizumabStandard of Care
cetuximabStandard of Care

Purpose

In this study, participants with MSI-H or dMMR advanced colorectal carcinoma 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) compared to current SOC chemotherapy.

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabExperimentalParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years)
    Standard of CareActive ComparatorPer Investigator choice, participants receive 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6 + bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6 + cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI + bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI + cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle
    • mFOLFOX6
    • FOLFIRI

    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
    
              -  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 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 SOC therapy or 120 days after the last pembrolizumab dose
    
              -  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 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
    
              -  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 or 120 days after the last dose of pembrolizumab
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Progression-free Survival (PFS)
    Time Frame:Up to 57 months
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Overall Response Rate (ORR)
    Time Frame:Up to 57 months
    Safety Issue:
    Description:
    Measure:Overall Survival (OS)
    Time Frame:Up to 57 months
    Safety Issue:
    Description:

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Merck Sharp & Dohme Corp.

    Trial Keywords

    • PD1
    • PDL1
    • PD-L1

    Last Updated

    April 26, 2017