Clinical Trials /

Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Previously-Treated Locally Advanced Unresectable or Metastatic Colorectal Cancer (MK-3475-164/KEYNOTE-164)

NCT02460198

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title:Study of Pembrolizumab (MK-3475) as Monotherapy in Participants With Previously-Treated Locally Advanced Unresectable or Metastatic Colorectal Cancer (MK-3475-164/KEYNOTE-164)
  • Official Title:A Phase II Study of Pembrolizumab (MK-3475) as Monotherapy in Subjects With Previously Treated Locally Advanced Unresectable or Metastatic (Stage IV) Mismatched Repair Deficient or Microsatellite Instability-High Colorectal Carcinoma (KEYNOTE-164)

Clinical Trial IDs

  • ORG STUDY ID: 3475-164
  • SECONDARY ID: 2015-001852-32
  • SECONDARY ID: 153046
  • NCT ID: NCT02460198

Trial Conditions

  • Colorectal Carcinoma

Trial Interventions

DrugSynonymsArms

Trial Purpose

In this study, participants with previously-treated locally-advanced unresectable or metastatic mismatched repair (MMR) deficient or microsatellite instability (MSI) high 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.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab: Cohort AExperimentalParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years).
    Pembrolizumab: Cohort BExperimentalParticipants receive pembrolizumab 200 mg IV on Day 1 Q3W for up to 35 cycles (approximately 2 years).

      Eligibility Criteria

      Inclusion criteria:

      - Histologically-proven locally advanced unresectable or metastatic high colorectal carcinoma

      - Locally confirmed MMR deficient or MSI status

      - Have 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

      - Eastern Cooperative Oncology Group performance status of 0 or 1

      - Life expectancy of greater than 3 months

      - Provide an archival or newly obtained tumor tissue sample (Cohort B)

      - At least one measureable lesion

      - Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication

      - Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study medication

      - 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 medication in this study, or used an investigational device within 4 weeks of the first dose of medication in this study

      - 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 the first dose of study medication

      - Known active central nervous system (CNS) 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 due to a previously administered agent

      - Prior therapy with an anti-programmed cell death (PD)-1, anti-PD ligand 1 (anti-PD-L1), or anti-PD-L2 agent

      - Known additional malignancy that is progressing or requires active treatment with the exception of 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 medication

      - Known history of human immunodeficiency virus (HIV)

      - Known active Hepatitis B or C

      - Known history 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 trial

      - Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial medication

      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:Both
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST 1.1) assessed by central imaging vendor
      Time Frame:Up to 2 years
      Safety Issue:No
      Description:

      Secondary Outcome Measures

      Measure:Disease Control Rate (DCR) per RECIST 1.1 assessed by central imaging vendor
      Time Frame:Up to 2 years
      Safety Issue:No
      Description:
      Measure:Duration of Response (DOR) per RECIST 1.1 assessed by central imaging vendor
      Time Frame:Up to 2 years
      Safety Issue:No
      Description:
      Measure:Progression-Free Survival (PFS) per RECIST 1.1 assessed by central imaging vedor
      Time Frame:Up to 2 years
      Safety Issue:No
      Description:
      Measure:Overall Survival (OS)
      Time Frame:Up to 2 years
      Safety Issue:No
      Description:

      Trial Keywords

      • PD1
      • PD-1
      • PDL1
      • PD-L1