Overview

This trial is active, not recruiting.

Conditions gastric adenocarcinoma, gastroesophageal junction adenocarcinoma
Treatments pembroliziumab, paclitaxel
Phase phase 3
Target PD-1
Sponsor Merck Sharp & Dohme Corp.
Start date May 2015
End date December 2017
Trial size 720 participants
Trial identifier NCT02370498, 152988, 2014-005241-45, 3475-061

Summary

This is a study for participants with advanced gastric or gastroesophageal junction adenocarcinoma who have had tumor progression after first-line treatment with platinum and fluoropyrimidine doublet therapy. The primary study hypotheses are that pembrolizumab prolongs progression free survival (PFS) and overall survival (OS) for participants with tumors that show positive programmed cell death ligand 1 (PD-L1) expression.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification 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 21-day cycle, for up to 35 administrations (approximately 2 years)
pembroliziumab
(Active Comparator)
Participants receive paclitaxel 80 mg/m^2 IV, on Days 1, 8, and 15 of each 28-day cycle.
paclitaxel

Primary Outcomes

Measure
PFS in PD-L1-positive Participants by Central Radiology Review
time frame: Up to 3 years
OS in PD-L1-positive Participants
time frame: Up to 3 years

Secondary Outcomes

Measure
PFS for All Participants by Central Radiology Review
time frame: Up to 3 years
OS in All Participants
time frame: Up to 3 years
PFS by Investigator Assessment
time frame: Up to 3 years
PFS Using Immune-related Response Assessment by Central Radiology Review
time frame: Up to 3 years
Time to Tumor Progression (TTP) by Investigator Assessment
time frame: Up to 3 years
TTP Using Immune-response Related Assessment by Central Radiology Review
time frame: Up to 3 years
Overall Response Rate (ORR) by Investigator Assessment
time frame: Up to 3 years
ORR Using Immune-related Response Assessment by Central Radiology Review
time frame: Up to 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Have histologically- or cytologically-confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma - Confirmed metastatic or locally advanced, unresectable disease (by CT scan or clinical evidence) - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Progression on or after prior first-line therapy containing any platinum/fluoropyrimidine doublet - Willing to provide tumor tissue for PD-L1 biomarker analysis (new or archived specimens with agreement of Sponsor) - HER-2/neu status known and participants with HER2/neu positive tumors show documentation of disease progression on treatment containing trastuzumab - 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 pembrolizumab or through 180 days after the last dose of paclitaxel. - 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 pembrolizumab or through 180 days after the last dose of paclitaxel. - 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 medication - Squamous cell or undifferentiated gastric cancer - Active autoimmune disease that has required systemic treatment in past 2 years (replacement therapy is not considered a form of systemic treatment - 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 - 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 not recovered from adverse events due to a previously administered agent or surgery - Known additional malignancy that is progressing or requires active treatment (with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy) - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis - History or 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 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 pembrolizumab or through 180 days after the last dose of paclitaxel. - Prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) clinical trial - Known history of human immunodeficiency virus (HIV) - Known active Hepatitis B or Hepatitis C - Live vaccine within 30 days of planned start of study therapy - Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy

Additional Information

Official title A Phase III, Randomized, Open-label Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel in Subjects With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Who Progressed After First-Line Therapy With Platinum and Fluoropyrimidine
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Merck Sharp & Dohme Corp..