KEYNOTE-811 Phase 3 Success: Extending Survival for First-Line HER2+ Gastric or GEJ Cancer

Merck's KEYTRUDA® (pembrolizumab), an anti-PD-1 therapy, has demonstrated significant progress in the Phase 3 KEYNOTE-811 trial. The trial, which combines pembrolizumab with trastuzumab and chemotherapy, has shown a notable improvement in overall survival (OS) for patients with HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. This advancement has led to the accelerated FDA approval for the first-line treatment of such patients, whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

The final analysis of KEYNOTE-811 revealed that the pembrolizumab combination therapy significantly outperformed the placebo in terms of OS for the intention-to-treat (ITT) population. The benefits were particularly pronounced among patients with PD-L1 expressing tumors (CPS ≥1). The safety profile of pembrolizumab was consistent with previous studies, with no new safety concerns identified. The results are expected to be presented at an upcoming medical conference and shared with global regulatory authorities.

The development is a significant step forward for patients with advanced gastric cancer, who often face a grim prognosis and have limited treatment options. Dr. Marjorie Green, from Merck Research Laboratories, emphasized the importance of these results, which build on earlier data showing improvements in progression-free survival, overall response rate, and duration of response.

KEYTRUDA has also been approved for the first-line treatment of HER2-negative gastric or GEJ adenocarcinoma in the U.S., based on the KEYNOTE-859 trial outcomes. Merck continues to expand its clinical development program for KEYTRUDA in various gastrointestinal cancers, including gastric, hepatobiliary, esophageal, and colorectal.

Gastric cancer is a slow-developing disease that often goes unnoticed until it reaches an advanced stage, with over 70% of patients diagnosed at this late stage. It is the fifth most common cancer and the fifth leading cause of cancer deaths globally. The five-year survival rate for advanced gastric cancer is a mere 7%.

KEYTRUDA works by enhancing the body's immune system to detect and combat tumor cells. It is a humanized monoclonal antibody that targets the PD-1 pathway, thereby activating T-lymphocytes that can affect both tumor and healthy cells.

Merck's extensive immuno-oncology clinical research program includes over 1,600 trials investigating KEYTRUDA across a range of cancers and treatment settings. The program aims to understand KEYTRUDA's role in various cancers and to identify factors that may predict a patient's response to treatment, including the exploration of different biomarkers.

Safety information for KEYTRUDA highlights the potential for severe and fatal immune-mediated adverse reactions. These reactions can occur in any organ system and can affect more than one body system simultaneously. It is crucial to monitor patients closely for symptoms and manage them promptly to ensure the safe use of anti-PD-1/PD-L1 treatments.