Merck (NYSE:MRK) and partner Eisai have announced the discontinuation of a study assessing the combination of Merck’s PD-1 inhibitor, Keytruda, and Eisai’s TKI inhibitor, Lenvima, as a first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
Over an 11-month period, an independent Data Monitoring Committee (DMC) conducted two planned interim analyses of the phase III LEAP-010 study, which evaluated overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) as primary endpoints. While the Keytruda plus Lenvima arm showed statistically significant improvements in PFS and ORR in the first analysis, the combination failed to demonstrate an OS improvement compared to Keytruda plus placebo in the second analysis. The likelihood of reaching the protocol-defined threshold for statistical significance for OS was also low. Due to the lack of an overall survival benefit for patients, Merck and Eisai have decided to terminate the study.
Another ongoing study, LEAP-009, is examining Keytruda plus Lenvima versus chemotherapy for treating recurrent or metastatic HNSCC that progressed after platinum therapy and immunotherapy.
Merck’s stock has seen a 0.7% decline this year, in contrast to the industry’s 7.6% increase.
At present, Keytruda plus Lenvima is approved in the US, the EU, Japan, and other countries for treating advanced renal cell carcinoma and specific types of advanced endometrial carcinoma. The combination is being studied for various tumor types.
In April, Merck and Eisai discontinued another phase III study, LEAP-003, investigating Keytruda-Lenvima combo as a first-line treatment for unresectable or metastatic melanoma. The combination failed to show an improvement in OS, one of the study’s primary endpoints, compared to Keytruda alone, as per DMC’s recommendation.
Additionally, the phase III LEAP-017 study evaluating Keytruda plus Lenvima for unresectable and metastatic colorectal cancer did not meet its primary endpoint of OS.
In a separate announcement, Merck revealed the initiation of the comprehensive phase III program CORALreef for MK-0616, an oral PCSK9 inhibitor developed for hypercholesterolemia treatment. Enrollment has started in two registrational phase III studies, CORALreef Lipids and CORALreef HeFH, focusing on reducing low-density lipoprotein (LDL) or “bad” cholesterol. Another phase III cardiovascular outcomes study, CORALreef Outcomes, is planned to commence by the end of 2023. The CORALreef program aims to enroll approximately 17,000 participants across three global studies. MK-0616 exhibited significant LDL cholesterol-lowering activity in a phase II trial across various patients with atherosclerotic cardiovascular disease. It has potential as a once-daily oral pill targeting PCSK9 for LDL cholesterol reduction, filling a gap as there are currently no oral PCSK9 inhibitors available in the market.
Featured Image: Megapixl @ Michaelvi
Author Stephanie Bédard-Châteauneuf 
