Merck's MK-1084 KRAS G12C Inhibitor Shows Antitumor Activity in Phase 1 Trial for Advanced Colorectal and Lung Cancer

Merck, known as MSD outside the United States and Canada, revealed promising results from its KANDLELIT-001 study, a Phase 1 clinical trial focused on MK-1084, an investigational KRAS G12C inhibitor. This study examines MK-1084 both as a standalone treatment and in combination with other therapies for patients with KRAS G12C-mutated solid tumors, including advanced colorectal cancer (CRC) and non-small cell lung cancer (NSCLC).

The preliminary findings from the KANDLELIT-001 trial demonstrate a manageable safety profile along with encouraging antitumor activity when MK-1084 is used alone or in combination with other treatments. "The early data from this study are promising, and we are eager to continue exploring the potential of MK-1084, both as a monotherapy and in combination with other treatments such as KEYTRUDA, for patients with KRAS mutations. These are some of the most common mutations in cancer," stated Dr. Marjorie Green, senior vice president and head of oncology at Merck Research Laboratories.

Continuing to explore innovative methods to assist cancer patients remains a priority for Merck, and these findings highlight the potential of their diverse and distinctive pipeline. In the study focusing on CRC, MK-1084 was evaluated on its own and in combination with cetuximab, with or without chemotherapy (including oxaliplatin, leucovorin, and 5-fluorouracil, known as mFOLFOX6). The study assessed the overall response rate (ORR) for patients whose conditions could be evaluated.

Regarding NSCLC, MK-1084 was studied both as a monotherapy and in combination with KEYTRUDA, with or without chemotherapy (carboplatin and pemetrexed), also evaluating ORR for patients. Overall, MK-1084 exhibited a manageable safety profile across all study arms. Treatment-related adverse events (TRAEs) were observed in various combinations: 58% of patients in the MK-1084 monotherapy arm, 94% in the arm combining MK-1084 and KEYTRUDA, 93% in the arm combining MK-1084 with KEYTRUDA and chemotherapy, 95% with MK-1084 and cetuximab, and 97% for MK-1084 combined with cetuximab and mFOLFOX6.

These findings from the KANDLELIT-001 study in CRC and NSCLC were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Looking ahead, MK-1084 will be further investigated in the Phase 3 KANDLELIT-012 study. This study will explore MK-1084 in combination with cetuximab and mFOLFOX6 for first-line treatment of patients with locally advanced, unresectable, or metastatic CRC with KRAS G12C-mutated tumors. Additionally, the Phase 3 KANDLELIT-004 study will assess MK-1084 in combination with KEYTRUDA for patients with metastatic NSCLC who have KRAS G12C-mutated tumors and express PD-L1.

MK-1084 is being developed through a collaboration and licensing agreement with Taiho Pharmaceutical Co. Ltd and Astex Pharmaceuticals, a subsidiary of Otsuka Pharmaceutical Co., Ltd. The KANDLELIT-001 study is a Phase 1, open-label, multicenter clinical trial designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of MK-1084 both as a monotherapy and in combination with other therapies in patients with KRAS G12C-mutated advanced solid tumors. The primary focus of the trial was on safety and tolerability, with secondary endpoints including objective response rate and duration of response.

With its focus on redefining cancer treatment through innovative research and a robust pipeline, Merck continues to strive for significant advancements in oncology, aiming to address unmet medical needs and improve outcomes for cancer patients worldwide.