Overview

This trial is active, not recruiting.

Condition colorectal carcinoma
Treatment pembrolizumab
Phase phase 2
Target PD-1
Sponsor Merck Sharp & Dohme Corp.
Start date August 2015
End date May 2017
Trial size 120 participants
Trial identifier NCT02460198, 153046, 2015-001852-32, 3475-164

Summary

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.

United States Illinois and New York
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years).
pembrolizumab MK-3475
IV infusion
(Experimental)
Participants receive pembrolizumab 200 mg IV on Day 1 Q3W for up to 35 cycles (approximately 2 years).
pembrolizumab MK-3475
IV infusion

Primary Outcomes

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

Secondary Outcomes

Measure
Disease Control Rate (DCR) per RECIST 1.1 assessed by central imaging vendor
time frame: Up to 2 years
Duration of Response (DOR) per RECIST 1.1 assessed by central imaging vendor
time frame: Up to 2 years
Progression-Free Survival (PFS) per RECIST 1.1 assessed by central imaging vedor
time frame: Up to 2 years
Overall Survival (OS)
time frame: Up to 2 years

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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)
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Merck Sharp & Dohme Corp..