Merck Initiates Phase III Trial to Test KRAS Inhibitor Against Competitors

Merck has initiated a Phase III clinical trial to assess the efficacy of a new oral drug, MK-1084, designed to target a specific mutation in non-small cell lung cancer (NSCLC) patients. The trial is set to test the drug in conjunction with Keytruda, a well-known PD-1 inhibitor, on patients who exhibit the PD-L1 protein and have a tumor proportion score of 50% or more. The study aims to enroll 600 participants and is expected to conclude in 2029.

The primary endpoints of the trial will focus on progression-free survival and overall survival, with secondary outcomes including the objective response rate, duration of response, and the patients' quality of life. Additionally, the safety of MK-1084 when combined with Keytruda will be evaluated.

The decision to advance MK-1084 to late-stage trials was based on early indications that the drug, when combined with Keytruda, has a manageable safety profile and shows promising anti-tumor activity. MK-1084 is a potent inhibitor of the G12C-mutated KRAS gene, which is involved in cell growth and division signaling pathways. The G12C mutation is a common genetic anomaly in NSCLC, present in approximately 14% of cases.

The KRAS gene has been historically challenging to target, with previous attempts considered unsuccessful. However, recent advancements have led to the development of targeted therapies. Amgen's Lumakras was the first to receive regulatory clearance for a KRAS G12C therapy, but faced issues with its confirmatory trial, leading to the FDA denying full approval in December 2023.

In contrast, BMS's Krazati demonstrated significant improvement in progression-free survival in a confirmatory Phase III study, positioning it as a leading contender in the KRAS treatment space. Originally developed by Mirati Therapeutics, Krazati became part of BMS following a $4.8 billion acquisition in 2023.

The ongoing research and development in the field of KRAS-targeted therapies represent a significant advancement in the treatment of NSCLC, offering hope for more effective cancer treatments in the future.