Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Previously-Treated Locally Advanced Unresectable or Metastatic Colorectal Cancer (MK-3475-164/KEYNOTE-164)
Condition: Colorectal Carcinoma
MeSH terms: Carcinoma; Colorectal Neoplasms
Intervention: Pembrolizumab
Intervention description: IV infusion
Intervention MeSH terms: Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 124.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); MSI-H; MSI

Summary:

      In this study, participants with previously-treated locally-advanced unresectable or
      metastatic mismatched repair (MMR) deficient or microsatellite instability-high (MSI-H)
      colorectal carcinoma (CRC) will be treated with pembrolizumab (MK-3475, KEYTRUDA®)
      monotherapy.

      There will be two cohorts in this study: Cohort A and Cohort B. For Cohort A, participants
      are required to have been previously treated with standard therapies, which must include
      fluoropyrimidine, oxaliplatin, and irinotecan. Enrollment into Cohort A has been completed.
      For Cohort B, participants are required to have been previously treated with at least one
      line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine
      + irinotecan +/ - anti-vascular endothelial growth factor (VEGF)/ epidermal growth factor
      regulator (EGFR) monoclonal antibody.

      The primary hypothesis is that Objective Response Rate (ORR) based on Response Evaluation
      Criteria in Solid Tumors v 1.1 (RECIST 1.1) assessed by central imaging vendor in
      participants with locally advanced unresectable or metastatic MMR deficient or MSI high CRC
      is greater than 15%.
    

Eligibility criteria:

        Inclusion criteria:

          -  Histologically-proven locally advanced unresectable or metastatic colorectal carcinoma

          -  Locally confirmed MMR deficient or MSI-H status

          -  Has been previously treated with standard therapies, which must include, for Cohort A,
             fluoropyrimidine, oxaliplatin, and irinotecan, and for Cohort B, at least one line of
             systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine
             + irinotecan +/- anti-VEGF/EGFR monoclonal antibody (mAb).

          -  Eastern Cooperative Oncology Group performance status of 0 or 1

          -  Life expectancy of greater than 3 months

          -  Provides an archival or newly obtained (≤60 days prior to first dose of study
             treatment) tumor tissue sample (Cohort B)

          -  At least one measurable lesion

          -  Female participants of childbearing potential should be willing to use acceptable
             methods of contraception or be surgically sterile, or abstain from heterosexual
             activity for the course of the study through 120 days after the last dose of study
             treatment

          -  Male participants should agree to use an adequate method of contraception starting
             with the first dose of study treatment through 120 days after the last dose of study
             treatment

          -  Adequate organ function

        Exclusion criteria:

          -  Currently participating in another study and receiving trial treatment, participated
             in a study of an investigational agent and received trial treatment within 4 weeks of
             the first dose of treatment in this study, or used an investigational device within 4
             weeks of the first dose of treatment in this study

          -  Active autoimmune disease that has required systemic treatment in past 2 years

          -  Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other
             form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment

          -  Known active central nervous system metastases and/or carcinomatous meningitis

          -  Prior monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or
             radiation therapy within 2 weeks prior to study Day 1 or not recovered (i.e., ≤ Grade
             1 or at baseline) from adverse events (AEs) due to a previously administered agent

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  Received a live vaccine within 30 days of planned start of study treatment

          -  Known history of human immunodeficiency virus (HIV)

          -  Known active Hepatitis B or C

          -  Has known history of, or any evidence of interstitial lung disease or active,
             noninfectious pneumonitis

          -  Active infection requiring systemic therapy

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the study

          -  Pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 120 days
             after the last dose of study treatment