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

• ClinicalTrials.gov Identifier: NCT02335411
• Recruitment Status: Active, not recruiting
• First Posted: January 9, 2015
• Last Update Posted: May 21, 2020
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Tracking Information

• First Submitted Date: January 7, 2015
• First Posted Date: January 9, 2015
• Last Update Posted Date: May 21, 2020
• Actual Study Start Date: February 3, 2015
• Estimated Primary Completion Date: July 23, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 10, 2015)

• 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 ]

Original Primary Outcome Measures (submitted: January 7, 2015)

• 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 ]
• Overall Response Rate (ORR) [ Time Frame: Up to 36 months ]

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Pembrolizumab (MK-3475) in Participants With Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-059/KEYNOTE-059)
• 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)
• 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).
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma

Intervention

• 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®

Study Arms

• 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
  Intervention: Biological: pembrolizumab
• 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
  Interventions:

  • Biological: pembrolizumab
  • Drug: cisplatin
  • Drug: 5-FU
  • Drug: capecitabine
• 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
  Intervention: Biological: pembrolizumab

Publications *

• Bang YJ, Kang YK, Catenacci DV, Muro K, Fuchs CS, Geva R, Hara H, Golan T, Garrido M, Jalal SI, Borg C, Doi T, Yoon HH, Savage MJ, Wang J, Dalal RP, Shah S, Wainberg ZA, Chung HC. Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study. Gastric Cancer. 2019 Jul;22(4):828-837. doi: 10.1007/s10120-018-00909-5. Epub 2019 Mar 25.
• Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH. Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer: Phase 2 Clinical KEYNOTE-059 Trial. JAMA Oncol. 2018 May 10;4(5):e180013. doi: 10.1001/jamaoncol.2018.0013. Epub 2018 May 10. Erratum in: JAMA Oncol. 2019 Apr 1;5(4):579.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 21, 2020): 315
• Original Estimated Enrollment (submitted: January 7, 2015): 270
• Estimated Study Completion Date: July 23, 2021
• Estimated Primary Completion Date: July 23, 2021 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: Australia, Canada, Chile, Colombia, Estonia, France, Israel, Italy, Japan, Korea, Republic of, Lithuania, Peru, Portugal, Romania, Russian Federation, United Kingdom, United States

Administrative Information

• NCT Number: NCT02335411
• Other Study ID Numbers: 3475-059; 2014-003574-16 ( EudraCT Number ); MK-3475-059 ( Other Identifier: Merck ); KEYNOTE-059 ( Other Identifier: Merck )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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

• Responsible Party: Merck Sharp & Dohme Corp.
• Study Sponsor: Merck Sharp & Dohme Corp.
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

• PRS Account: Merck Sharp & Dohme Corp.
• Verification Date: May 2020