One of the top selling drugs in the world, Merck’s anti-PD-1 therapy KEYTRUDA (pembrolizumal), is moving into new territory. The company just reported positive topline results from a phase III trial 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 trial’s primary endpoint of overall survival (OS) versus chemotherapy alone in the all-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 full results will be presented at an upcoming medical meeting and will be submitted to regulatory authorities.
The drug’s safety profile trial was consistent with that observed in previously reported studies, with no new safety signals being identified. These results put the drug pretty much neck-neck with Astellas Pharma’s zolbetuximab. A Phase III trial of that drug in CLDN18.2-positive and HER2-negative advanced gastric or GEJ adenocarcinoma recently also 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 nods for seven new indications in each of 2021 and 2020 for a total of almost 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 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 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. The results from KEYNOTE-859 show the potential of KEYTRUDA plus chemotherapy to improve survival beyond chemotherapy alone for patients with HER2-negative locally advanced unresectable or metastatic gastric or 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. Trials include KEYNOTE-811 in first-line advanced HER2-positive gastric cancer, KEYNOTE-585 in early-stage gastric cancer, and in advanced/metastatic gastric cancer in LEAP-015. Merck reports it is also continuing to study KEYTRUDA for multiple uses in hepatobiliary, esophageal, pancreatic, and colorectal cancers.
Earlier last year, the FDA granted an accelerated approval for Keytruda for HER2-positive gastric cancer in the first-line setting, in combination with trastuzumab, fluoropyrimidine- and platinum-based chemo. That approval came after positive results from a study in 264 patients not previously treated for their disease.
KEYNOTE-859 is a randomized, double-blind Phase III 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 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.
Merck currently has more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings and exploring several different biomarkers of response to the drug.