Efficacy and Safety Study of Pembrolizumab (MK-3475) Versus Paclitaxel in Asian Participants With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma Who Progressed After First-line Therapy With Platinum and Fluoropyrimidine (MK-3475-063/KEYNOTE-063)
Condition: Gastric Neoplasms; Gastroesophageal Junction Adenocarcinoma
MeSH terms: Adenocarcinoma; Esophageal Neoplasms; Stomach Neoplasms
Intervention: Pembrolizumab; Paclitaxel
Intervention description: IV infusion; IV infusion
Intervention MeSH terms: Paclitaxel; Pembrolizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 94.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Summary:

      The study will compare the efficacy and safety of treatment with pembrolizumab (MK-3475)
      versus paclitaxel in Asian, programmed death-ligand 1 (PD-L1) positive participants with
      advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who have progressed after
      failure of any combination chemotherapy containing a platinum and a fluoropyrimidine agent.

      The primary study hypotheses are that pembrolizumab prolongs Overall Survival (OS) compared
      to paclitaxel and that pembrolizumab prolongs Progression-free Survival (PFS) per Response
      Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by blinded central
      radiologists' review compared to paclitaxel.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has histologically or cytologically-confirmed diagnosis of gastric or GEJ
             adenocarcinoma.

          -  Has metastatic disease or locally advanced, unresectable disease.

          -  Has measurable disease as defined by RECIST 1.1 as determined by investigator.

          -  Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale within 3 days prior to the first dose of study treatment.

          -  Has experienced documented objective radiographic or clinical disease progression
             during or after first-line therapy containing any platinum/fluoropyrimidine doublet.

          -  Is willing to provide tissue for PD-L1 biomarker analysis.

          -  Has PD-L1 positive tumor (based on analysis of sample provided to core lab).

          -  Female participants of childbearing potential must 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 treatment for the
             pembrolizumab arm and through 180 days after the last dose of study treatment for the
             paclitaxel arm.

          -  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 study
             treatment for the pembrolizumab arm and through 180 days after the last dose of study
             treatment for the paclitaxel arm.

          -  Demonstrates adequate organ function.

        Exclusion Criteria:

          -  Is currently participating and receiving study therapy or has 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 trial treatment.

          -  Has squamous cell or undifferentiated gastric cancer.

          -  Has active autoimmune disease that has required systemic treatment in past 2 years.

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the
             first dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at
             Baseline) from AEs due to agents administered more than 4 weeks earlier.

          -  Has had prior chemotherapy, targeted small molecule therapy, radiation therapy, or any
             other agents used as systemic treatment for cancer, within 2 weeks prior to the first
             dose of trial treatment or who has not recovered (i.e., ≤ Grade 1 or at Baseline) from
             AEs due to a previously administered agent.

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 5 years. Exceptions include basal cell carcinoma of the skin, squamous
             cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially
             curative therapy.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis.

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Is 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 treatment for the pembrolizumab arm and through 180 days
             after the last dose of study treatment for the paclitaxel arm.

          -  Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1),
             anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or
             co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4
             [CTLA-4], OX-40, CD137).

          -  Has a known history of Human Immunodeficiency Virus (HIV) infection.

          -  Has known active Hepatitis B or C virus infection.

          -  Has received a live vaccine within 30 days of planned start of study treatment.

          -  Has known allergy or hypersensitivity to paclitaxel or any components used in the
             paclitaxel preparation or other contraindication for taxane therapy.