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)

Not Recruiting

Trial ID: NCT02563002


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.

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)

Stanford Investigator(s)

George A. Fisher Jr.
George A. Fisher Jr.

Colleen Haas Chair in the School of Medicine

Hans-Christoph Becker, MD, FSABI, FSCCT

Clinical Professor, Radiology


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

   - 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)


drug: mFOLFOX6


biological: pembrolizumab

biological: bevacizumab

biological: cetuximab

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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