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)

Inclusion Criteria:

Inclusion criteria include, but are not limited to:

• Histologically or cytologically confirmed diagnosis of previously untreated, locallyadvanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)positive gastric or gastroesophageal junction (GEJ) adenocarcinoma

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

• Has measurable disease as defined by Response Evaluation Criteria in Solid Tumorsversion 1.1 (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 awoman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approvedcontraception

• 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:

Exclusion criteria include, but are not limited to:

• Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJcancer

• Has had major surgery, open biopsy or significant traumatic injury within 28 daysprior to randomization, or anticipation of the need for major surgery during thecourse of study treatment

• Has had radiotherapy within 14 days of randomization

• Has a known additional malignancy that is progressing or has required activetreatment within the past 5 years

• Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis

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

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

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

• 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 ordiuretic drugs within 2 weeks prior to enrollment. If the participant is receivingdiuretic drugs for other reasons, it is acceptable

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the trial, interfere with theparticipant's participation for the full duration of the trial, or is not in thebest interest of the participant to participate, in the opinion of the treatinginvestigator

• Has peripheral neuropathy > Grade 1

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

• A WOCBP who has a positive urine pregnancy test within 24 hours prior torandomization or treatment allocation

• 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] isdetected) infection

• Has severe hypersensitivity (≥Grade 3) to pembrolizumab, trastuzumab, studychemotherapy agents and/or to any excipients, murine proteins, orplatinum-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 orwith 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 ofDifferentiation 137 [CD137])