By Connor Lynch

Pictured: Merck logo on building/iStock, Sundry Photography

Merck and Eisai have dropped another joint drug trial after disappointing Phase III results. The companies announced Friday that they would be ending their combination treatment of Keytruda and Lenvima, respectively, after a second interim analysis found no improvement in overall survival.
The LEAP-010 trial was evaluating the safety and effectiveness of Merck’s anti-PD-1 therapy in combination with Eisai’s multiple receptor tyrosine kinase inhibitor for metastatic or unresectable head and neck squamous cell carcinoma (HNSCC). An independent monitoring committee conducted two interim analyses over the course of 11 months.
Initial results from the first analysis were promising: the therapy combo met two of the trial’s three primary endpoints of progression-free survival and objective response (OS) rate.
However, the treatment failed to show evidence of meeting the third endpoint, overall survival, in the second analysis. The companies in Friday’s announcement said “the likelihood of reaching the protocol-specified threshold for statistical significance for OS was evaluated by Merck and Eisai and deemed to be low.” As a result, the study is being closed and “the companies are informing investigators of this decision.”
At the same time, the announcement noted that these results do not affect other ongoing LEAP trials, including the Phase II LEAP-009 trial which is evaluating the therapy combo alongside chemotherapy in patients with recurrent or metastatic HNSCC who progressed after platinum therapy and immunotherapy.
It’s not the first investigative avenue for the combination treatment that hasn’t panned out. The Phase III LEAP-003 trial investigating the two therapies to treat advanced melanoma and metastatic colorectal cancer was shut down in April 2023 after no improvement in overall survival was observed compared to treatment with Keytruda alone.
In August 2022, the companies closed their Phase III LEAP-002 trial for patients with unresectable hepatocellular carcinoma after it failed to meet primary endpoints of overall survival and progression-free survival.
Keytruda is a monoclonal antibody that works by activating T lymphocytes, increasing the body’s natural response against cancer. Lenvima is a tyrosine kinase inhbitor which interferes with tumor growth and cancer progression by inhibiting kinases implicated in pathogenic angiogenesis.
Both treatments are approved separately on their own for treatments of various cancers. The combination of treatments is already approved in the U.S., Europe, and Japan for treatment of advanced renal cell carcinoma, as well as certain types of advanced endometrial carcinoma.
The LEAP program of clinical trials overall is investigating the drug combination in a variety of cancers, including endometrial carcinoma, hepatocellular carcinoma, non-small cell lung cancer, gastric cancer and esophageal cancer, among others.