Merck Announces Phase 3 KEYNOTE-811 Trial Results at ESMO 2023: Pembrolizumab Plus Trastuzumab and Chemotherapy for First-Line Treatment of HER2-Positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

MSD Presents Phase III Clinical Trial KEYNOTE-811 Data at ESMO

This study aims to evaluate the treatment regimen of pembrolizumab combined with trastuzumab and chemotherapy for first-line treatment of locally advanced unresectable or metastatic HER-2 positive gastric cancer or gastroesophageal junction adenocarcinoma.

Rahway, New Jersey, USA, October 20, 2023 — MSD (the corporate name of Merck & Co., Inc. in Rahway, New Jersey, USA) announced the Phase III clinical trial KEYNOTE-811 study data. The study aims to evaluate the treatment regimen of MSD's PD-1 inhibitor pembrolizumab in combination with trastuzumab and chemotherapy for first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric cancer or gastroesophageal junction adenocarcinoma. The study data were simultaneously presented at the 2023 European Society for Medical Oncology Annual Meeting (ESMO2023).

Dr. Yelena Y. Janjigan

Chief of Gastrointestinal Surgery at Memorial Sloan Kettering Cancer Center, Global Principal Investigator of KEYNOTE-811 Study

Most patients with gastric cancer are diagnosed at an advanced stage and have often faced a poor prognosis in the past. The results of the KEYNOTE-811 study further explore the prospects of using pembrolizumab combined with trastuzumab and chemotherapy in PD-L1 CPS ≥1 patients with advanced HER-2 positive status.

According to global cancer statistics released in 2020, gastric cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide: In 2020, there were approximately 1.1 million new cases and 760,000 deaths globally; of these, China accounted for 478,000 new cases and nearly 374,000 deaths, representing 43.9% and 48.6% of the global total of new cases and deaths from gastric cancer, respectively. Gastric cancer is a heterogeneous disease with significant individual differences, and the proportion of HER-2 overexpression in gastric cancer patients ranges from 4.4% to 53.4%, with an average of approximately 17.9%.

Dr. Marjorie Green

Senior Vice President of Merck & Co., Inc. Research Laboratories and Late-Stage Oncology,

Global Head of Clinical Development

The KEYNOTE-811 study, aimed at evaluating treatment options for advanced HER-2 positive gastric cancer or gastroesophageal junction adenocarcinoma with PD-L1 CPS≥1, further underscores our commitment to exploring the field of refractory gastric cancer treatment.

KEYNOTE-811 Study is a randomized, double-blind, Phase III clinical trial designed to evaluate the treatment regimen of pembrolizumab combined with trastuzumab and chemotherapy as first-line therapy for locally advanced unresectable or metastatic HER2-positive gastric cancer/gastroesophageal junction adenocarcinoma. The primary endpoints are progression-free survival (PFS) and overall survival (OS), while the secondary endpoints are objective response rate (ORR) and duration of response (DoR). The study enrolled 692 patients, who were randomly assigned in a 1:1 ratio to either the pembrolizumab + trastuzumab + chemotherapy group or the placebo + trastuzumab + chemotherapy group.

References:
1. As of now, the National Medical Products Administration (NMPA) has approved the following indications for pembrolizumab, and other indications have not yet been approved:
For the treatment of unresectable or metastatic melanoma that has failed first-line therapy;
Approved by the National Medical Products Administration (NMPA) for first-line monotherapy in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are negative for epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK), with a PD-L1 tumor proportion score (TPS) ≥1% as assessed by a validated test.
In combination with pemetrexed and platinum-based chemotherapy, it is indicated for the first-line treatment of metastatic non-squamous non-small cell lung cancer (NSCLC) that is negative for epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK).
Combination of carboplatin and paclitaxel is applicable for first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC);
In combination with platinum and fluorouracil chemotherapy drugs for the first-line treatment of patients with locally advanced unresectable or metastatic esophageal or gastroesophageal junction cancer;
As a monotherapy for the treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (Combined Positive Score (CPS) ≥10) as assessed by a test approved by the National Medical Products Administration (NMPA), and who have failed prior first-line systemic therapy.
As a single agent for the first-line treatment of patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 (Combined Positive Score (CPS) ≥20) as determined by a validated assay.
Monotherapy for the first-line treatment of patients with KRAS, NRAS, and BRAF wild-type, unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer (CRC);
Monotherapy for the treatment of advanced hepatocellular carcinoma (HCC) patients who have previously received sorafenib or oxaliplatin-based chemotherapy.
Neoadjuvant treatment with combination chemotherapy followed by adjuvant treatment with pembrolizumab monotherapy after surgery, for the treatment of patients with early-stage high-risk triple-negative breast cancer (TNBC) whose tumors express PD-L1 (Combined Positive Score (CPS) ≥20) as assessed by a validated test.
For adult patients with unresectable or metastatic high microsatellite instability (MSI-H) or mismatch repair-deficient (dMMR) advanced solid tumors: colorectal cancer patients whose disease has progressed after prior treatment with fluorouracil, oxaliplatin, and irinotecan; other solid tumors that have progressed after prior treatment and have no satisfactory alternative treatment options. This indication received conditional approval based on surrogate endpoints and has not yet obtained clinical endpoint data. The efficacy and safety remain to be further confirmed post-marketing.
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Editor: Bai Ji

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