Overview

This trial is active, not recruiting.

Conditions gastric adenocarcinoma, gastroesophageal junction adenocarcinoma
Treatments pembrolizumab, cisplatin, 5-fu, capecitabine
Phase phase 2
Target PD-1
Sponsor Merck Sharp & Dohme Corp.
Start date February 2015
End date November 2016
Trial size 253 participants
Trial identifier NCT02335411, 2014-003574-16, 3475-059

Summary

This is a study of pembrolizumab for advanced gastric or gastroesophageal junction adenocarcinoma; pembrolizumab will be given as monotherapy to participants who have had previous treatment or who are treatment-naïve; pembrolizumab will also be evaluated as combination therapy with cisplatin and 5-Fluorouracil (5-FU) or (Japan only) capecitabine in treatment-naïve participants. The primary study hypothesis is that pembrolizumab will provide a clinically meaningful overall response rate.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 24 months
pembrolizumab
(Experimental)
Participants receive pembrolizumab 200 mg IV Q3W for up to 24 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-FU 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3 week cycle
pembrolizumab
cisplatin
5-fu
capecitabine
(Experimental)
Participants receive pembrolizumab 200 mg IV Q3W for up to 24 months
pembrolizumab

Primary Outcomes

Measure
Number of Participants Experiencing Adverse Events (AEs)
time frame: Up to 25 months
Number of Participants Discontinuing Study Drug Due to AEs
time frame: Up to 24 months
Objective Response Rate (ORR)
time frame: Up to 36 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria Cohort 1: - Received and progressed on at least 2 prior chemotherapy regimens for their advanced disease; prior regimen must have included a cisplatin and a fluoropyridine - Human epidermal growth factor receptor 2 (HER-2/neu) negative, or, if HER2/neu positive, must have previously received treatment with trastuzumab Inclusion Criteria Cohort 2 or 3: - HER2/neu negative - Has not received prior systemic anti-cancer therapy for their advanced carcinoma (systemic therapy received in the neoadjuvant and adjuvant setting does not count) Inclusion Criteria All Participants: - Histologically- or cytologically-confirmed recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma that is considered incurable by local therapies - Willing to provide tissue for PD-L1 biomarker analysis from newly-obtained and/or archival tissue - Measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to first dose of study medication - Life expectancy of >= 3months - Female participants of childbearing potential should have a negative pregnancy test and 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 (180 days for participants receiving cisplatin + 5FU) - Male participants should agree to use an adequate method of contraception starting with the first dose through 120 days after the last dose of study medication (180 days for participants receiving cisplatin + 5FU) - Adequate organ function Exclusion Criteria: - Currently participating and receiving study therapy or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study medication - Active autoimmune disease that has required systemic treatment in past 2 years - Immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication - Weight loss >10% over 2 months prior to first dose of study medication - Clinical evidence of ascites by physical exam - Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from adverse events due to agents administered more than 4 weeks earlier - Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered from adverse events due to a previously administered agent - Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Known history of, or any evidence of active, non-infectious pneumonitis - Active infection requiring systemic therapy - 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 trial, starting with the screening visit through 120 days after the last dose of study medication (180 days for participants receiving cisplatin + 5FU) - Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent - Human immunodeficiency virus (HIV) - Hepatitis B or C - Received live vaccine within 30 days of planned start of study medication

Additional Information

Official title A Phase II Clinical Trial of Pembrolizumab as Monotherapy and in Combination With Cisplatin+5-Fluorouracil in Subjects With Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE-059)
Description This study will have 3 cohorts. Cohorts 1 and 2 will run simultaneously; Cohort 3 will start when biomarker assay validation is complete. In Cohort 1, participants who have received at least two prior therapies for their advanced disease will receive monotherapy with pembrolizumab. In Cohort 2, participants who have not received any previous therapy for their disease will receive pembrolizumab in combination with cisplatin and 5-FU or (Japan only) capecitabine. In Cohort 3, participants who have not received any previous therapy and who have programmed cell death ligand 1 (PD-L1)-positive tumors will receive monotherapy with pembrolizumab.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Merck Sharp & Dohme Corp..