Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-811/KEYNOTE-811)

Pembrolizumab (200 mg) or placebo will be administered intravenously [IV] on day 1 of each
3-week cycle. Trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance dose) will be
administered IV on day 1 of each 3-week cycle. SOC chemotherapy for the global cohort will
either be FP (80 mg/m^2 cisplatin administered IV on Day 1 of each 3-week cycle and 800
mg/m^2 5-fluorouracil [5-FU] administered IV on Days 1-5 of each 3-week cycle) or CAPOX (1000
mg/m^2 capecitabine administered orally twice daily [BID] on days 1-14 of each 3-week cycle
and 130 mg/m^2 oxaliplatin administered IV on Day 1 of each 3-week cycle). A Japan cohort
will receive SOX chemotherapy consisting of S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine
[CDHP], and potassium oxonate [Oxo]) administered orally BID according to Body Surface Area
(BSA) on Days 1-14 of each 3-week cycle and oxaliplatin (130 mg/m^2) administered IV on Day 1
each 3-week cycle.

Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of previously untreated, locally
advanced unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma

- HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination
with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization
(FISH), as assessed by central review on primary or metastatic tumor

- Has measurable disease as defined by RECIST 1.1 as determined by the site investigator

- Male participants must agree to use approved contraception

- Female participants who are not pregnant or breastfeeding, and who are either not a
woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved
contraception

- 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 trial treatment

- Has a life expectancy of greater than 6 months

- Has adequate organ function

Exclusion Criteria:

- Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ
cancer

- Has had 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

- Has had radiotherapy within 14 days of randomization

- Has a known additional malignancy that is progressing or has required active treatment
within the past 5 years

- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis

- Has an active autoimmune disease that has required systemic treatment in past 2 years

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis

- Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)

- Has an active infection requiring systemic therapy

- Has poorly controlled diarrhea

- Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic
drugs within 2 weeks prior to enrollment. If the participant is receiving diuretic
drugs for other reasons, it is acceptable

- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the participant's
participation for the full duration of the trial, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator

- Has peripheral neuropathy > Grade 1

- Has a known psychiatric or substance abuse disorder that would interfere with
cooperation with the requirements of the trial

- A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization
or treatment allocation

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 7 months
after the last dose of trial treatment

- Has active or clinically significant cardiac disease

- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)

- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection

- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, trastuzumab, study
chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing
products

- Has had an allogeneic tissue/solid organ transplant

- Has received prior therapy with an 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, Cluster of
Differentiation 137 [CD137])