Merck's KEYNOTE-811 Trial Meets Primary Endpoint for HER2+ Gastric/GEJ Cancer

Merck, known as MSD outside the United States and Canada, has announced that its Phase 3 KEYNOTE-811 trial has achieved a significant milestone in the fight against advanced gastric cancer. The trial evaluated the efficacy of KEYTRUDA® (pembrolizumab), an anti-PD-1 therapy, in combination with trastuzumab and fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. According to the company, the trial met its dual primary endpoint of overall survival (OS).

Based on these results, KEYTRUDA has been approved in the United States for use in combination with trastuzumab and chemotherapy as a first-line treatment for adults with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma whose tumors express PD-L1 (CPS ≥1). This approval was granted under the FDA’s accelerated approval regulations, which take into account the objective response rate (ORR) and the durability of response. Continued approval may depend on further verification and description of clinical benefits in the final analysis of the KEYNOTE-811 study.

The final analysis showed that the combination of KEYTRUDA, trastuzumab, and chemotherapy led to a statistically significant and clinically meaningful improvement in overall survival compared to a placebo plus trastuzumab and chemotherapy. The most notable benefits were observed in patients whose tumors expressed PD-L1 (CPS ≥1). Importantly, the safety profile of KEYTRUDA in this trial was consistent with previous studies, with no new safety concerns identified. Detailed results from the trial will be presented at an upcoming medical conference and shared with global regulatory authorities.

Dr. Marjorie Green, Senior Vice President and Head of Oncology, Global Clinical Development at Merck Research Laboratories, emphasized the importance of these findings, noting that advanced gastric cancer often carries a poor prognosis. She highlighted that the overall survival results from KEYNOTE-811 are encouraging and build on previously reported data on progression-free survival, overall response rate, and duration of response.

In an earlier interim analysis, the KEYNOTE-811 trial had already met its other dual primary endpoint of progression-free survival (PFS), results of which were presented at the European Society for Medical Oncology (ESMO) Congress 2023.

In the United States, KEYTRUDA is also approved for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma, based on results from the KEYNOTE-859 trial. Merck is actively pursuing an extensive clinical development program to evaluate KEYTRUDA across various gastrointestinal cancers, including gastric, hepatobiliary, esophageal, and colorectal cancers.

The KEYNOTE-811 trial is a randomized, double-blind Phase 3 study that enrolled 698 patients. Participants were divided into two groups: one group received KEYTRUDA (200 mg every three weeks) in combination with trastuzumab and chemotherapy, while the other group received a placebo in combination with trastuzumab and chemotherapy. The dual primary endpoints of the trial were progression-free survival (PFS) and overall survival (OS), with secondary endpoints including objective response rate (ORR), duration of response, and safety.

Gastric cancer, often developing slowly over many years, is typically diagnosed at an advanced stage due to its lack of early symptoms. The disease is the fifth most diagnosed cancer globally and the fifth leading cause of cancer death. In 2022, approximately 969,000 patients were diagnosed with gastric cancer, resulting in 660,000 deaths worldwide. In the United States, it is estimated that in 2024, around 26,890 new cases of gastric cancer will be diagnosed, with 10,880 resulting in death. The five-year survival rate for those diagnosed at an advanced stage is only 7%.

KEYTRUDA is known for its role in enhancing the body's immune response against tumor cells by blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2. This inhibition activates T lymphocytes, which can affect both tumor and healthy cells. Merck is conducting over 1,600 trials to study KEYTRUDA across various cancers and treatment settings.