One of the world’s best-selling drugs, Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumal), is moving into new territory. The company just reported positive results from a Phase III study of KEYTRUDA in combination with chemotherapy for patients with human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Patients who received the combination showed a clinically meaningful improvement in the study’s primary endpoint of overall survival (OS) compared to chemotherapy alone in the randomized patient population. Statistically significant and clinically meaningful improvements in progression-free survival (PFS) and overall response rate (ORR) were also observed. The company says the full findings will be presented at an upcoming medical meeting and will be submitted to regulators.
The study drug safety profile was consistent with that observed in previously reported studies, with no new safety signals identified. These results put the drug practically neck and neck with Astellas Pharma’s zolbetuximab. A phase III study of that drug in CLDN18.2-positive and HER2-negative advanced gastric adenocarcinoma or GEJ also recently reported positive results.
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. Since its first FDA approval in 2016, the drug has received nominations for seven new indications in each of 2021 and 2020 for a total of nearly 20 cancer approvals.
Gastric cancer is the fifth most diagnosed cancer and the fourth leading cause of cancer death worldwide, with nearly 1.1 million new cases diagnosed and more than 768,000 deaths from the disease globally in 2020. In the United States , it is estimated that 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 late-stage gastric cancer is just six percent.
“Despite improvements in cancer care, advanced gastric cancer continues to have one of the lowest five-year survival rates, and new interventions are urgently needed. Results from KEYNOTE-859 show the potential of KEYTRUDA plus chemotherapy to improve survival beyond chemotherapy alone for patients with unresectable or metastatic locally advanced or HER2-negative gastroesophageal junction adenocarcinoma, regardless of PD-L1 expression” said Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories.
Merck has an extensive clinical development program evaluating KEYTRUDA in gastrointestinal cancers. The studies include KEYNOTE-811 in first-line advanced HER2-positive gastric cancer, KEYNOTE-585 in early stage gastric cancer, and advanced/metastatic gastric cancer in LEAP-015. Merck reports that it is also continuing to investigate KEYTRUDA for multiple uses in hepatobiliary, esophageal, pancreatic and colorectal cancers.
Earlier last year, the FDA granted accelerated approval for Keytruda for HER2-positive gastric cancer in the first-line setting, in combination with trastuzumab, fluoropyrimidine and platinum chemotherapy. That approval came after positive results from a study involving 264 patients who had not previously been treated for their disease.
KEYNOTE-859 is a randomized, double-blind, Phase III study (ClinicalTrials.gov, NCT03675737) evaluating KEYTRUDA in combination with chemotherapy versus placebo in combination with chemotherapy for the first-line treatment of patients with locally advanced HER2-negative non resectable or metastatic gastric adenocarcinoma or GEJ. The study enrolled 1,579 patients who were randomized to receive KEYTRUDA (200 mg every three weeks for up to approximately two years) in combination with platinum-fluoropyrimidine-containing chemotherapy or placebo in combination with chemotherapy.
Merck currently has more than 1,600 studies investigating KEYTRUDA in a wide variety of cancers and treatment settings and exploring different drug response biomarkers.