A Study of Pembrolizumab (MK-3475) in Participants With Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-059/KEYNOTE-059)
Condition: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma
MeSH terms: Adenocarcinoma; Esophageal Neoplasms
Intervention: pembrolizumab; cisplatin; 5-FU; capecitabine
Intervention description: IV infusion; IV infusion; IV infusion; oral tablets
Intervention MeSH terms: Pembrolizumab; Capecitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 318.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gastric cancer; Gastroesophageal junction cancer; Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

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).
    

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 at least 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