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)

Completed · Phase 3 · Has a placebo group

Conditions studied: Gastric Neoplasms, Gastroesophageal Junction Adenocarcinoma

In brief

The study will compare the efficacy and safety of pembrolizumab plus trastuzumab in combination with standard of care (SOC) chemotherapy versus trastuzumab in combination with SOC chemotherapy in participants with HER2-positive gastric cancer. The primary hypotheses of the study are that pembrolizumab plus trastuzumab in combination with chemotherapy is superior to trastuzumab plus chemotherapy in terms of 1) progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR), and 2) overall survival (OS).

Key facts

Study ID: NCT03615326
Run by: Merck Sharp & Dohme LLC
People needed: 738
Starts: 2018-10-05
Expected to finish: 2025-11-12
Last updated by the study team: 2025-12-11

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Inclusion criteria include, but are not limited to:
Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced 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+ 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 Response Evaluation Criteria in Solid Tumors version 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 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

You may not qualify if…

Exclusion criteria include, but are not limited to:
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 24 hours prior to randomization 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] 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])

Where it is running

Pacific Cancer Care ( Site 0063) — Monterey, California, United States
UC Irvine Medical Center/Chao Family Comprehensive Cancer Center ( Site 0050) — Orange, California, United States
University of Miami Sylvester Comprehensive Cancer Center - Plantation ( Site 0026) — Miami, Florida, United States
Southeastern Regional Medical Center, Inc. ( Site 0058) — Newnan, Georgia, United States
Midwestern Regional Medical Center, Inc. ( Site 0059) — Zion, Illinois, United States
Beth Israel Deaconess Medical Center ( Site 0070) — Boston, Massachusetts, United States
Dana-Farber Cancer Institute [Boston, MA] ( Site 0010) — Boston, Massachusetts, United States
Minnesota Oncology Hematology, PA ( Site 8001) — Minneapolis, Minnesota, United States
Washington University School of Medicine ( Site 0040) — St Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center- Monmouth ( Site 0071) — Middletown, New Jersey, United States
Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 0065) — Harrison, New York, United States
Memorial Sloan-Kettering Cancer Center ( Site 0017) — New York, New York, United States
University of Rochester ( Site 0041) — Rochester, New York, United States
Levine Cancer Institute ( Site 0015) — Charlotte, North Carolina, United States
Duke Cancer Institute ( Site 0042) — Durham, North Carolina, United States
CTCA Southwestern ( Site 0060) — Tulsa, Oklahoma, United States
Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0025) — Philadelphia, Pennsylvania, United States
Allegheny General Hospital ( Site 0053) — Pittsburgh, Pennsylvania, United States
Sanford Hematology Oncology-Sioux Falls SD ( Site 0004) — Sioux Falls, South Dakota, United States
University of Texas MD Anderson Cancer Center ( Site 0001) — Houston, Texas, United States
Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care ( Site 8000) — Roanoke, Virginia, United States
Seattle Cancer Care Alliance ( Site 0038) — Seattle, Washington, United States
Liverpool Hospital ( Site 2206) — Liverpool, New South Wales, Australia
Westmead Hospital ( Site 2200) — Westmead, New South Wales, Australia
UCLA Hematology/Oncology - Westwood (Building 200 Suite 120) ( Site 0045) — Los Angeles, California, United States

Full record on ClinicalTrials.gov

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