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A Study of Pembrolizumab (MK-3475) in Participants With Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-059/KEYNOTE-059)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02335411
Recruitment Status : Active, not recruiting
First Posted : January 9, 2015
Last Update Posted : May 21, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Description
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Brief Summary:
This is a study of pembrolizumab (MK-3475) 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 (ORR).

Condition or disease Intervention/treatment Phase
Gastric Adenocarcinoma Gastroesophageal Junction Adenocarcinoma Biological: pembrolizumab Drug: cisplatin Drug: 5-FU Drug: capecitabine Phase 2

Detailed 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 death ligand 1 (PD-L1)-positive tumors will receive pembrolizumab monotherapy.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 315 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 3, 2015
Estimated Primary Completion Date : July 23, 2021
Estimated Study Completion Date : July 23, 2021

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1: Pembro monotherapy, previously treated
Participants receive pembrolizumab (Pembro) 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 24 months
 Biological: pembrolizumab
IV infusion
Other Name: MK-3475
Experimental: Cohort 2: Pembro combination therapy, treatment naive
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
 Biological: pembrolizumab
IV infusion
Other Name: MK-3475

Drug: cisplatin
IV infusion
Other Name: PLATINOL®

Drug: 5-FU
IV infusion
Other Name: ADRUCIL®

Drug: capecitabine
oral tablets
Other Name: XELODA®
Experimental: Cohort 3: Pembro monotherapy, treatment naive
Participants receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 24 months
 Biological: pembrolizumab
IV infusion
Other Name: MK-3475


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 25 months ]
  2. Number of Participants Discontinuing Study Drug Due to AEs [ Time Frame: Up to 24 months ]
  3. Objective Response Rate (ORR) [ Time Frame: Up to 36 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria - Cohort 1:

  • Received and progressed on ≥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 drug
  • Life expectancy of >=3 months
  • 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 drug (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 drug (180 days for participants receiving cisplatin + 5FU)
  • Adequate organ function

Exclusion Criteria - All Participants:

  • 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 drug
  • 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 drug
  • Weight loss >10% over 2 months prior to first dose of study drug
  • 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 AEs 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 AEs 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 study, starting with the screening visit through 120 days after the last dose of study drug (180 days for participants receiving cisplatin + 5FU)
  • Prior therapy with an anti-programmed death-1 (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 drug
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02335411


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02335411    
Other Study ID Numbers: 3475-059
2014-003574-16 ( EudraCT Number )
MK-3475-059 ( Other Identifier: Merck )
KEYNOTE-059 ( Other Identifier: Merck )
First Posted: January 9, 2015    Key Record Dates
Last Update Posted: May 21, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Gastric cancer
Gastroesophageal junction cancer
PD1
 PD-1
PDL1
PD-L1
Additional relevant MeSH terms:
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Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
 Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Capecitabine
Pembrolizumab
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological