The unsuccessful Phase III results are the latest to suggest that the blockbuster cancer drug is finally bumping up against its limits after racking up around 50 approvals since getting its first FDA nod in September 2014.
Merck’s mega blockbuster Keytruda paired with Eisai’s Lenvima did not improve overall survival in a Phase III clinical trial of patients with an advanced form of gastroesophageal adenocarcinoma. While the trial did show an improvement in progression-free survival (PFS), the results add to a growing body of clinical data suggesting that Keytruda is reaching the limits of its widespread use.
Keytruda was first approved by the FDA in September 2014 for advanced melanoma. Since then, the PD-1 inhibitor broke open the immuno-oncology space, racking up some four dozen approvals for a suite of cancer types, including breast cancer, colorectal cancer, renal cell carcinoma, lung cancer and many more, often as part of combo therapies and often paired with cancer drugs from other companies.
But recently Merck’s Keytruda luck has turned. The company halted a Phase III trial of Keytruda plus anti-TIGIT antibody vibostolimab and chemotherapy in patients with extensive-stage small cell lung cancer in August 2024 after data showed it would not meet the primary endpoint of overall survival. In the fall, an FDA committee recommended limiting the use of Keytruda and Bristol Myers Squibb rival med Opdivo in stomach and esophageal cancers based on PD-L1 expression levels.
In the latest study to readout, Keytruda was paired with Eisai’s tyrosine kinase inhibitor (TKI) Lenvima in patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastroesophageal adenocarcinoma. The late-stage trial, called LEAP-015, showed a statistically significant improvement in PFS at the interim analysis as compared to placebo, the companies said in a Friday release. This was one of the study’s two primary endpoints. It also showed improvement in objective response rate (ORR), which was a secondary endpoint.
But the combo did not meet the other primary endpoint of overall survival, which is a measure of how long a patient survives after starting treatment. Specific survival data were not disclosed.
Merck’s Gregory Lubiniecki, vice president of global clinical development at the pharma’s research branch, chalked up the results to the challenges of advanced gastroesophageal adenocarcinoma and said in the release that the results add to the companies’ understandings of this combination. Eisai’s Corina Dutcus, senior VP and oncology global clinical development lead, similarly noted that these cancers present challenges “due to their heterogeneity and generally poor prognoses.”
The companies will conduct a full analysis of the data and report results at an upcoming medical meeting.
Keytruda and Lenvima are approved together for patients with advanced renal cell carcinoma and certain types of endometrial carcinoma. The companies are also studying the combo in hepatocellular carcinoma and esophageal cancer in the broader LEAP clinical program.
