Clinical trial · Interventional
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)
A Phase III, Randomized, Double-blind Trial Comparing Trastuzumab Plus Chemotherapy and Pembrolizumab With Trastuzumab Plus Chemotherapy and Placebo as First-line Treatment in Participants With HER2 Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (KEYNOTE 811)
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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).
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Gastric Neoplasms | Gastric Neoplasm | ONTOLOGY_EXACT | 0.98 |
| Gastroesophageal Junction Adenocarcinoma | Gastroesophageal Junction Adenocarcinoma | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (8)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| 5-FU | Drug | Fluorouracil | ALIAS |
| Capecitabine | Drug | Capecitabine | ALIAS |
| Cisplatin | Drug | Cisplatin | ALIAS |
| Oxaliplatin | Drug | Oxaliplatin | ALIAS |
| Pembrolizumab | Biological | Pembrolizumab | ALIAS |
| Placebo | Biological | — | UNRESOLVED |
| S-1 | Drug | — | UNRESOLVED |
| Trastuzumab | Biological | Trastuzumab | ALIAS |
Design
Arms and outcomes
Arms (4)
- type
- EXPERIMENTAL
- label
- Global Pembrolizumab + Standard of Care First Course
- description
- Participants received 200 mg pembrolizumab IV every 3 weeks (Q3W) plus trastuzumab (8 mg/kg loading dose, 6 mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy.
- interventionNames
- Biological: Pembrolizumab
- Drug: Cisplatin
- Drug: 5-FU
- Drug: Oxaliplatin
- Drug: Capecitabine
- Biological: Trastuzumab
- type
- ACTIVE_COMPARATOR
- label
- Global Standard of Care
- description
- Participants received matched placebo to pembrolizumab IV Q3W plus trastuzumab (8mg/kg loading dose, 6mg/kg maintenance thereafter) IV Q3W in combination with investigator's choice of FP or CAPOX chemotherapy.
- interventionNames
- Biological: Placebo
- Drug: Cisplatin
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: 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 Exclusion Criteria: 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 \[CD137\])
References
Publications (4)
- RESULTJanjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin SK, Van Cutsem E, Tabernero J, Li K, Shih CS, Bhagia P, Rha SY; KEYNOTE-811 Investigators. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastro-oesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebo-controlled trial. Lancet. 2023 Dec 9;402(10418):2197-2208. doi: 10.1016/S0140-6736(23)02033-0. Epub 2023 Oct 20. PMID 37871604
- RESULTJanjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Wyrwicz LS, Shen L, Ostapenko Y, Bilici M, Chung HC, Shitara K, Qin S, Van Cutsem E, Tabernero J, Luo S, Mahave M, Tang Y, Lowery M, Monteiro MMF, Xu L, Shih CS, Sharan KP, Bhagia P, Rha SY. Pembrolizumab in HER2-Positive Gastric Cancer. N Engl J Med. 2024 Oct 10;391(14):1360-1362. doi: 10.1056/NEJMc2408121. Epub 2024 Sep 14. No abstract available. PMID 39282917
- DERIVEDJanjigian YY, Kawazoe A, Yanez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. doi: 10.1038/s41586-021-04161-3. Epub 2021 Dec 15. PMID 34912120
- DERIVEDChung HC, Bang YJ, S Fuchs C, Qin SK, Satoh T, Shitara K, Tabernero J, Van Cutsem E, Alsina M, Cao ZA, Lu J, Bhagia P, Shih CS, Janjigian YY. First-line pembrolizumab/placebo plus trastuzumab and chemotherapy in HER2-positive advanced gastric cancer: KEYNOTE-811. Future Oncol. 2021 Feb;17(5):491-501. doi: 10.2217/fon-2020-0737. Epub 2020 Nov 10. PMID 33167735