Study of Pembrolizumab (MK-3475) as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-062/KEYNOTE-062)
Condition: Gastric Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Pembrolizumab; Cisplatin; 5-FU; Capecitabine; Placebo
Intervention description: Pembrolizumab 200 mg IV on Day 1 of each week in 3-week cycles for up to 35 cycles (approximately 2 years).; Cisplatin 80 mg/m^2 IV on Day 1 of each week in 3-week cycles (6 cycle maximum per local country guidelines).; 5-FU 800 mg/m^2/day IV continuous from Day 1-5 of each 3-week cycle.; Capecitabine 1000 mg/m^2 twice daily by oral tablet on Day 1-14 of each 3-week cycle.; Normal saline IV on Day 1 of each week in 3-week cycles for up to 35 cycles (approximately 2 years).
Intervention MeSH terms: Pembrolizumab; Capecitabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: This study is partially blinded. The participant, study site personnel, and the sponsor will be blinded in the pembrolizumab plus SOC chemotherapy (pembro combo) arm and the placebo plus SOC chemotherapy (SOC) arm, but not in the pembro monotherapy (mono arm) since only one type of study medication will be administered.
Enrollment: 763.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gastric carcinoma; Gastric cancer; Gastroesophageal junction cancer; Gastroesophageal junction carcinoma; Programmed Cell Death-1 (PD1, PD-1),; Programmed Death-Ligand 1 (PDL1, PD-L1); Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)

Summary:

      This is a study of pembrolizumab (MK-3475) as first-line treatment for participants with
      advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Participants whose tumors
      express programmed death-ligand 1 (PD-L1) will be randomly assigned to one of the three
      treatment arms of the study: pembrolizumab as monotherapy [pembro mono], pembrolizumab plus
      standard of care (SOC) chemotherapy with cisplatin plus 5-fluorouracil (5-FU) or capecitabine
      [pembro combo], or placebo plus SOC chemotherapy with cisplatin plus 5-fluorouracil (5-FU) or
      capecitabine [SOC].

      The primary study hypotheses are that pembrolizumab in combination with SOC chemotherapy is
      superior to SOC chemotherapy alone in terms of Progression-free Survival (PFS) and Overall
      Survival (OS) in participants with PD-L1 Combined Positive Score (CPS) ≥1, pembrolizumab in
      combination with SOC chemotherapy is superior to SOC chemotherapy alone in terms of OS in
      participants with PD-L1 CPS ≥10, pembrolizumab monotherapy is non-inferior to SOC
      chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥1, and pembrolizumab
      monotherapy is superior to SOC chemotherapy alone in terms of OS in participants with PD-L1
      CPS ≥1 and in participants with PD-L1 CPS ≥10.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             Performance Scale within 3 days prior to first dose of study medication

          -  Has histologically- or cytologically-confirmed diagnosis of locally advanced
             unresectable or metastatic gastric or GEJ adenocarcinoma

          -  Human epidermal growth factor receptor 2- (HER2/neu-) negative and programmed cell
             death ligand 1 (PD-L1)-positive

          -  Has measurable disease

          -  Female participants of childbearing potential must be willing to use adequate
             contraception or be surgically sterile, or abstain from heterosexual activity for the
             course of the study through 120 days after the last dose of study medication

          -  Male participants of childbearing potential should agree to use an adequate method of
             contraception starting with the first dose of study medication through 120 days after
             the last dose of study medication

          -  Adequate organ function

        Exclusion Criteria:

          -  Squamous cell or undifferentiated gastric cancer

          -  Previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer.
             Participant may have received prior neoadjuvant or adjuvant therapy as long as it was
             completed at least 6 months prior to randomization

          -  Major surgery, open biopsy or significant traumatic injury within 28 days prior to
             randomization, or anticipation of the need for major surgery during the course of
             study treatment.

          -  Radiotherapy within 14 days of randomization

          -  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
             that has undergone potentially curative therapy or in situ cervical cancer

          -  Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

          -  Active autoimmune disease that has required systemic treatment in past 2 years

          -  Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in
             dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior the first dose of study medication

          -  History of non-infectious pneumonitis that required steroids or current pneumonitis

          -  Active infection requiring systemic therapy

          -  Pregnant, 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 study medication

          -  Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, or anti-PD-L2
             agent

          -  Known history of human immunodeficiency virus (HIV)

          -  Known active Hepatitis B or C

          -  Currently participating in and receiving study therapy or has participated in a study
             of an investigational agent or has used an investigational device within 4 weeks prior
             to the first dose of study medication

          -  Received a live vaccine within 30 days prior to the first dose of study medication