FDA Grants Accelerated Approval to Merck’s Keytruda Combination Therapy for First-Line Treatment of HER2-Positive Gastric Cancer

Merck Sharp & Dohme (MSD) announced today that the U.S. FDA has granted accelerated approval for its anti-PD-1 therapy Keytruda in combination with trastuzumab and fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. The press release noted that this is the first anti-PD-1 therapy approved in combination with trastuzumab and chemotherapy for the first-line treatment of this patient population. This marks another significant advancement in the field, following the approval in April of Bristol Myers Squibb’s (BMS) blockbuster PD-1 inhibitor Opdivo (nivolumab) in combination with chemotherapy for the first-line treatment of patients with gastric cancer.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. In China, it is the second most prevalent cancer after lung cancer. The incidence and mortality rates of gastric cancer in China account for 44% and 50% of the global totals, respectively. Eighty percent of Chinese patients with gastric cancer are already at an advanced stage at the time of diagnosis. For the majority of patients with advanced gastric cancer, chemotherapy has remained the first-line treatment option over the past few decades. However, the efficacy of chemotherapy is limited, and the five-year survival rate for patients with advanced or metastatic gastric cancer is only 5%.

Keytruda is a blockbuster anti-PD-1 therapy developed by MSD. It activates T lymphocytes by blocking the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby enhancing the human immune system’s ability to detect and eliminate cancer cells.

This accelerated approval is supported by the ongoing randomized, double-blind, placebo-controlled clinical trial KEYNOTE-811. Interim analysis results showed that among the initial 264 randomly enrolled patients, the overall response rate (ORR) in the Keytruda combination therapy group reached 74%, significantly superior to the control group receiving placebo plus trastuzumab and chemotherapy (52%).

In terms of safety, 6% of patients in both the Keytruda combination therapy group and the control group discontinued the trial due to adverse reactions. The most common adverse reaction leading to permanent discontinuation of Keytruda was pneumonitis (1.4%). Adverse reactions leading to temporary interruption of Keytruda treatment occurred in 58% of patients. The most common adverse reactions or laboratory abnormalities leading to interruption of Keytruda treatment were neutropenia (18%), thrombocytopenia (12%), diarrhea (6%), anemia (3.7%), hypokalemia (3.7%), fatigue/asthenia (3.2%), decreased appetite (3.2%), increased aspartate aminotransferase (AST) (2.8%), increased blood bilirubin (2.8%), pneumonitis (2.8%), increased alanine aminotransferase (ALT) (2.3%), and vomiting (2.3%).

In the Keytruda group versus the placebo group, the incidence rates of diarrhea (53% vs. 44%), nausea (49% vs. 44%), elevated ALT (34% vs. 29%), and elevated creatinine (20% vs. 10%) differed by ≥5% between patients receiving Keytruda and those receiving standard care. There were no clinically meaningful differences in the incidence of Grade 3–4 adverse events between the two groups.

Note: The original text has been abridged.

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