Safety and Efficacy of Pembrolizumab (MK-3475) in Combination With TS-1+Cisplatin or TS-1+Oxaliplatin as First Line Chemotherapy in Gastric Cancer (MK-3475-659/KEYNOTE-659)
Condition: Gastric Cancer
MeSH terms: Stomach Neoplasms
Intervention: Pembrolizumab; Oxaliplatin; TS-1; Cisplatin
Intervention description: 200 mg Q3W on Day 1 by IV infusion; 130 mg/m^2 Q3W on Day 1 by IV infusion; 40 to 60 mg orally according to Body Surface Area (BSA) BID Q3W on Days 1-14; 60 mg/m^2 Q3W on Day 1 by IV infusion
Intervention MeSH terms: Pembrolizumab; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to estimate objective response rates (ORRs) of pembrolizumab +
      oxaliplatin + TS-1 and pembrolizumab + cisplatin + TS-1, as first-line treatment for gastric
      cancer in programmed death-ligand 1 (PD-L1) positive, human epidermal growth factor receptor
      2 (HER2/neu)-negative participants with advanced gastric or gastroesophageal junction (GEJ)
      adenocarcinoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Has histologically- or cytologically-confirmed diagnosis of locally advanced
             unresectable or metastatic gastric or GEJ adenocarcinoma

          -  Has a PD-L1 positive tumor as determined by immunohistochemistry (IHC) at a central
             laboratory

          -  Has measurable disease as defined by RECIST 1.1 as determined by investigator
             assessment. Tumor lesions situated in a previously irradiated area are considered
             measurable if progression has been demonstrated in such lesions

          -  Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy
             test at the timing of enrollment

          -  Participants of childbearing potential must be willing to use an adequate method of
             contraception for the course of the study through 120 days after the last dose of
             study medication

          -  Has adequate organ function

        Exclusion Criteria:

          -  Has squamous cell or undifferentiated gastric cancer

          -  HER2-positive status

          -  Has had previous therapy for locally advanced, unresectable or metastatic gastric/GEJ
             cancer

          -  A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation

          -  Has received prior therapy with a platinum-based anti-cancer drug

          -  Has had major surgery, open biopsy or significant traumatic injury within 28 days
             prior to enrollment, or anticipation of the need for major surgery during the course
             of study treatment

          -  Has had radiotherapy within 14 days of enrollment

          -  Has a known additional malignancy that is progressing or has required active treatment
             within the past 5 years

          -  Has clinically active central nervous system (CNS) metastases and/or carcinomatous
             meningitis

          -  Has an active autoimmune disease that has required systemic treatment in the past 2
             years with use of disease modifying agents, corticosteroids, or immunosuppressive
             drugs

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment

          -  Has a history of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis

          -  Has any active infection requiring systemic therapy

          -  Will be on flucytosine at the time of enrollment

          -  Has grade ≥ 2 peripheral sensory neuropathy

          -  Has poorly controlled diarrhea (e.g., watery stool, uncontrollable bowel movement with
             drugs, grade ≥ 2 and number of defecations, ≥ 5/day)

          -  Has accumulation of pleural, ascitic, or pericardial fluid requiring drainage within 2
             weeks prior to enrollment

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with participation for the
             full duration of the trial, or is not in the best interest of the participant, in the
             opinion of the treating investigator

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  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

          -  Has received prior therapy with an anti-programmed death (PD)-1, anti-PD-L1, or anti
             PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell
             receptor

          -  Has known history of human immunodeficiency virus (HIV) [HIV1/2 antibodies]

          -  Has a known history of Hepatitis B

          -  Has received live vaccine within 30 days of the planned start of study therapy

          -  Is currently participating in and receiving study therapy or has participated in a
             study of an investigational agent and received study therapy or used an
             investigational device within 4 weeks prior to the first dose of trial treatment