Merck (NYSE:MRK) and its partner Eisai have declared the discontinuation of a study centered on evaluating the combination of Merck’s prominent PD-1 inhibitor, Keytruda, and Eisai’s TKI inhibitor, Lenvima. This study aimed to assess their joint effectiveness 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) performed two planned interim analyses of the phase III LEAP-010 study. The study’s primary endpoints encompassed overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Although the first analysis revealed a statistically significant enhancement in two primary endpoints—PFS and ORR—in the Keytruda plus Lenvima group, the subsequent analysis showed that the Keytruda/Lenvima combination did not exhibit any improvement in OS compared to Keytruda in combination with a placebo. Moreover, the likelihood of attaining the protocol-specified threshold for statistical significance in OS was low. Given the absence of a demonstrated overall survival advantage for patients, Merck and Eisai have opted to conclude the study.
Concurrently, a separate study named LEAP-009 continues to explore the combination of Keytruda plus Lenvima versus chemotherapy for treating recurrent or metastatic HNSCC patients who have experienced progression after platinum therapy and immunotherapy.
In the stock market, Merck’s shares have experienced a 0.7% decline this year, in contrast to the industry’s overall rise of 7.6%.
At present, the Keytruda plus Lenvima combination is approved in multiple regions, including the United States, the EU, and Japan, for treating advanced renal cell carcinoma and specific types of advanced endometrial carcinoma. Furthermore, Lenvima is undergoing evaluation in combination with Keytruda for various other tumor types.
It is noteworthy that in April, Merck and Eisai terminated another phase III study known as LEAP-003. This study aimed to evaluate the combination of Keytruda and Lenvima as a first-line treatment for adults dealing with unresectable or metastatic melanoma. As per the DMC’s recommendation, the combination did not exhibit any improvement in OS, one of the study’s dual primary endpoints, when compared to Keytruda alone.
During the same period, Merck and Eisai also disclosed that the phase III LEAP-017 study, which was assessing Keytruda plus Lenvima for the treatment of patients with unresectable and metastatic colorectal cancer, did not achieve its primary endpoint of OS.
In a separate announcement, Merck revealed the initiation of a comprehensive phase III program named CORALreef for MK-0616, its oral PCSK9 inhibitor designed to address hypercholesterolemia. The program includes two registrational phase III studies—CORALreef Lipids and CORALreef HeFH—both focused on evaluating the reduction in low-density lipoprotein (LDL) or “bad” cholesterol. Additionally, Merck plans to commence another phase III study, CORALreef Outcomes, by the end of 2023, which will examine cardiovascular outcomes. The CORALreef program is expected to involve around 17,000 participants across three global studies. Notably, MK-0616 demonstrated statistically significant LDL cholesterol-lowering effects in a phase II study spanning a broad spectrum of patients with atherosclerotic cardiovascular disease. It holds the potential to be developed into a once-daily oral pill, targeting PCSK9 to lower LDL cholesterol—an avenue currently not addressed by oral PCSK9 inhibitors in the market.
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