Overview of the Mechanism of Action of MK-1084


Carlos Rojas, MD, discusses the mechanism of action of MK-1084, a selective KRAS G12C inhibitor.

Carlos Rojas, MD, medical oncology, Centro de Investigacion Clinica, Bradford Hill, in Santiago, Chile, discusses the mechanism of action of MK-1084, a selective KRAS G12C inhibitor.

The agent is currently undergoing evaluation in a phase 1 trial (NCT05067283) for patients with metastatic non-small cell lung cancer. In the study, MK-1084 is being evaluated alone and in combination with pembrolizumab (Keytruda) for the treatment of patients with advanced solid tumors and non-small cell lung cancer in the first-line setting.

Findings from this phase 1 trial were presented by Rojas at the 2023 ESMO Congress. As of April 5, 2023, there were no dose-limiting toxicities reported, and the overall response rate among the 43 patients included in arm 1was 19%. All of the responses were partial responses (PRs), including 4 patients with colorectal cancer and 4 with non-small cell lung cancer. Among the 15 patients in arm 2, the ORR was 47%, and all were PRs.


0:09 | This is a new drug that is an inhibitor [for use] in patients that have a mutation on KRAS, the specific mutation is G12C. We know that there are a few drugs on the market right now in the northern hemisphere, and this is a new drug. What we say about this drug is that it is active and we report similar results to the previous drug that was presented. Also and I think an important thing about this drug is safety. As monotherapy and in combination with pembrolizumab, we saw a very good tolerance, a low grade of grade 3 and 4 adverse events.

1:02 | [With] the combination, we did not see a high number of liver toxicity, it was like 10% of the patients on grade 3 or more than that. That is also good news because 1 of the problems with this drug is that in combination with pembrolizumab, in previous reports of other drugs combining with this PD-L1 inhibitor, we saw a lot of liver toxicity, and this was not a problem in this trial.

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