Merck announces positive results from phase 3 KEYNOTE-859 trial of Keytruda plus chemotherapy to treat patients with HER2-negative gastric or GEJ adenocarcinoma
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells.
Rahway: Merck, known as MSD outside of the United States and Canada, has announced results from the pivotal Phase 3 KEYNOTE-859 trial investigating KEYTRUDA, Merck's anti-PD-1 therapy, in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of patients with human epidermal growth factor receptor 2 (HER2)-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. After a median follow-up of 31.0 months (range, 15.3-46.3 months),
KEYTRUDA in combination with chemotherapy significantly improved overall survival (OS), reducing the risk of death by 22% (HR=0.78 [95% CI, 0.70-0.87]; p<0.0001) compared to chemotherapy alone for these patients, regardless of PD-L1 expression. Median OS was 12.9 months (95% CI, 11.9-14.0) for KEYTRUDA plus chemotherapy versus 11.5 months (95% CI, 10.6-12.1) for chemotherapy alone.
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
“Most gastric cancers go undetected until an advanced stage, at which point the five-year survival rate is just 6%, one of the lowest across cancer types,” said Dr. Sun Young Rha, director and professor of medical oncology in the Department of Internal Medicine, Songdang Institute for Cancer Research, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea. “The positive overall survival results observed in this study are very encouraging and demonstrate the potential of KEYTRUDA in combination with chemotherapy to extend the lives of patients with HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma.”
Results from the KEYNOTE-859 trial were generally consistent across pre-specified subgroups. In addition to an improvement in OS, results showed KEYTRUDA plus chemotherapy significantly improved progression-free survival (PFS) and objective response rate (ORR), which were both secondary endpoints of the trial, versus chemotherapy alone. Specifically, KEYTRUDA plus chemotherapy reduced the risk of disease progression or death by 24% (HR=0.76 [95% CI, 0.67-0.85]; p<0.0001) with a median PFS of 6.9 months (95% CI, 6.3-7.2) for KEYTRUDA plus chemotherapy compared to 5.6 months (95% CI, 5.5-5.7) for chemotherapy alone. The ORR was 51.3% (95% CI, 47.7-54.8), with a complete response (CR) rate of 9.5% and a partial response (PR) rate of 41.8%, for patients who received KEYTRUDA plus chemotherapy and 42.0% (95% CI, 38.5-45.5), with a CR rate of 6.2% and a PR rate of 35.7%, for those who received chemotherapy alone (p=0.00009). Median duration of response (DOR), another secondary endpoint of the trial, was 8.0 months (range, 1.2+-41.5+) for KEYTRUDA plus chemotherapy versus 5.7 months (range, 1.3+-34.7+) for chemotherapy alone.
“Eighty percent of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma have HER2-negative disease. Based on these new data, we hope to expand the use of KEYTRUDA and provide an option that, in combination with chemotherapy, may help more of these patients live longer,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “These results also reinforce our commitment to research in gastrointestinal cancers, where we continue to evaluate a number of KEYTRUDA-based combinations, including in earlier stages of disease.”
KEYTRUDA is approved in the U.S. in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Merck has an extensive clinical development program evaluating KEYTRUDA in gastrointestinal cancers, which includes KEYNOTE-811 in first-line advanced HER2-positive gastric cancer, KEYNOTE-585 in early-stage gastric cancer and further exploration in advanced/metastatic gastric cancer in combination with a tyrosine kinase inhibitor in LEAP-015. Merck is continuing to study KEYTRUDA for multiple uses in hepatobiliary, esophageal, pancreatic, colorectal and biliary tract cancers.
