Policy & Regulation
US Merck's Phase 3 KEYNOTE-859 Trial Met Primary Endpoint of Overall Survival in Patients with HER2-Negative Gastric or Gastroesophageal Junction Adenocarcinoma
22 November 2022 - - US-based pharmaceutical company Merck (NYSE: MRK) has released positive topline results from the pivotal Phase 3 KEYNOTE-859 trial investigating Keytruda, Merck's anti-PD-1 therapy, in combination with chemotherapy for the first-line treatment of patients with human epidermal growth factor receptor 2 -negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, the company said.

Keytruda in combination with chemotherapy showed a statistically significant and clinically meaningful improvement in the trial's primary endpoint of overall survival versus chemotherapy alone in the all-randomized patient population at a pre-specified interim analysis conducted by an independent Data Monitoring Committee.

Statistically significant and clinically meaningful improvements in progression-free survival and overall response rate were also observed in the all-randomized patient population.

The safety profile of Keytruda in this trial was consistent with that observed in previously reported studies; no new safety signals were identified. Results will be presented at an upcoming medical meeting and will be submitted to regulatory authorities.

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 LEAP-015.

Merck is continuing to study Keytruda for multiple uses in hepatobiliary, esophageal, pancreatic and colorectal cancers.

KEYNOTE-859 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03675737) evaluating Keytruda in combination with chemotherapy compared to placebo in combination with chemotherapy for the first-line treatment of patients with HER2-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.

The primary endpoint is OS, and secondary endpoints include PFS, ORR, duration of response and safety.

The trial enrolled 1,579 patients who were randomized to receive Keytruda (200 mg every three weeks for up to approximately two years) in combination with fluoropyrimidine- and platinum-containing chemotherapy, or placebo in combination with chemotherapy.

Gastric (stomach) cancer tends to develop slowly over many years and rarely causes early symptoms, resulting in most cases going undetected until an advanced stage.

More than 70% of patients with gastric cancer develop advanced-stage disease.

Most gastric cancers are adenocarcinomas (about 90-95%), which develop from cells in the innermost lining of the stomach (known as the mucosa).

Gastric cancer is the fifth most diagnosed cancer and the fourth leading cause of cancer death worldwide, with nearly 1.1m new cases diagnosed and more than 768,000 deaths from the disease globally in 2020.

In the US, it is estimated there will be more than 26,000 new cases of gastric cancer diagnosed and more than 11,000 deaths from the disease in 2022.

The five-year survival rate for patients diagnosed with gastric cancer at an advanced stage is only 6%.

Keytruda is an anti-programmed death receptor-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.

Merck has the industry's largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings.

The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers.