Dr Johnson on the Efficacy of RMC-6236 in KRAS-Mutant NSCLC

Melissa L. Johnson, MD, medical oncologist, Sarah Cannon Research Institute, discusses the preliminary efficacy findings from the phase 1 RMC-6236-001 trial (NCT05379985) in patients with non–small cell lung cancer (NSCLC) harboring KRAS mutations and details the significance of these findings for patients within the KRAS G12X-mutant NSCLC population.

At the 2023 ESMO Congress, data from the NSCLC and pancreatic ductal adenocarcinoma (PDAC) cohorts of the RMC-6236-001 trial were presented. RMC-6236 is a RAS ON inhibitor, and it therefore is selective for mutant and wild-type RAS isoforms in their active, GTP-bound ON state. The agent is under evaluation in RMC-6236-001 in patients with advanced solid tumors harboring KRAS G12X mutations, including KRAS G12D, KRAS G12V, and less common KRAS mutations, such as KRAS G12S and KRAS G12R, Johnson says. Patients with KRAS G12C–mutated disease are currently excluded from enrollment onto the trial, though this agent is hypothesized to potentially also be effective in this population, Johnson notes.

Investigators hypothesized that RMC-6236 would be active in the presence of any KRAS mutation, Johnson explained, adding that the preliminary findings show that the agent is effective in patients with NSCLC and PDAC. In the NSCLC cohort, the overall response rate with RMC-6236 was 38%, including best responses of complete response, partial response, and stable disease in 3%, 35%, and 48% of patients, respectively.

Patients with KRAS G12X–mutant NSCLC is often a difficult-to-treat patient population with first-line chemoimmunotherapy, Johnson emphasizes. All patients enrolled in the NSCLC cohort of the RMC-6236-001 trial had previously progressed on prior platinum-based chemotherapy, and 96% had progressed on a prior checkpoint inhibitor. Although patients with KRAS G12C–mutant NSCLC have several unmet needs, the KRAS G12X–mutant NSCLC population represents an area of even greater need, according to Johnson. Although the data from the RMC-6236-001 trial are still in early stages, further results from this trial may be presented in the future, Johnson concludes.