Manageable safety and encouraging antitumour responses were presented with MK-1084 monotherapy and combination regimens
Updated data from the phase I, open-label, multicenter KANDLELIT-001 study continued to show a manageable safety profile and an encouraging antitumour activity of the next-generation, selective KRAS G12C-GDP covalent inhibitor MK-1084, as monotherapy or in combination with other therapies, in patients with KRAS G12C-mutant advanced colorectal cancer (CRC). Findings were presented at the ESMO Asia Congress 2025 (Abstract 198MO), and are in line with preliminary data presented previously (J Clin Oncol 2025; 43, 3508-3508).
The study assessed MK-1084 as monotherapy in 58 patients with CRC who had received at least one prior systemic therapy (arm 1+3), in combination with cetuximab in 41 patients with advanced CRC who had received 1-2 prior systemic therapies (arm 5) and in combination with cetuximab and modified FOLFOX6 (oxaliplatin and leucovorin plus 5-fluorouracil) in 33 patients with advanced CRC and no or one prior systemic therapies (arm 6). Dose-limiting toxicities (DLTs) and safety were the primary endpoints.
DLTs occurred in 1 participant in the MK-1084 monotherapy arm and in 2 participants in the combination arm with mFOLFOX6. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 10% of patients in arms 1+3, 17% in arm 5, and 27% in arm 6, leading to treatment discontinuation in 1%, 2%, and 12%, respectively.
Confirmed objective response rate (ORR) was 38% with MK-1084 monotherapy and 46% with MK-1084 plus cetuximab. In the MK-1084 plus cetuximab and chemotherapy arm, ORR was 38% and limited by a short follow-up of median 4.6 months.
While recruitment to both combination regimens is still ongoing in this phase I study, the combination of MK-1084 plus cetuximab and mFOLFOX6 will be investigated against the standard-of-care as first-line treatment in the phase III MK-1084-012/KANDLELIT-012 trial (NCT06997497).
