Dr Arbour on the Safety and Efficacy of RMC-6236 in KRAS-Mutant NSCLC

Kathryn C. Arbour, MD, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses preliminary safety and efficacy data with the RAS inhibitor RMC-6236 in patients with KRAS-mutated non–small cell lung cancer (NSCLC).

At the 2023 ESMO Congress, Arbour presented findings from the phase 1 RMC-6236-001 trial (NCT05379985) which evaluated treatment with RMC-6236 at 80 mg and above in patients with NSCLC and pancreatic ductal adenocarcinoma (PDAC) harboring KRAS G12X mutations, excluding KRAS G12C mutations. Evaluating the safety profile of this agent in patients with NSCLC is important because the tolerability of pan-RAS inhibitors is unknown, Arbour says.

RMC-6236 was well tolerated at clinically active doses in patients with NSCLC, Arbour explains. The most common treatment-related adverse effects (TRAEs) reported in all safety-evaluable patients with NSCLC and PDAC treated with at least 80 mg of RMC-6236 per day (n = 111) were rash, nausea, diarrhea, vomiting, stomatitis, and fatigue, most of which were grade 1/2 and generally well managed with supportive medications such as topical steroids and oral antibiotics, Arbour notes. Importantly, only 14% of patients with NSCLC or PDAC required dose reduction because of TRAEs of any grade, and only 1 patient (1%) discontinued treatment due to TRAEs. The safety findings with RMC-6236 supplement the efficacy findings by showing that patients can maintain treatment with consistent doses of this agent, Arbour emphasizes.

Regarding the clinical activity of RMC-6236, of 40 patients with NSCLC who initiated treatment with RMC-6236 at 80 mg per day or more at least 8 weeks prior to data cutoff, 1 patient (3%) achieved a complete response, and 14 patients (35%) experienced a partial response, translating to an overall response rate of 38%. Furthermore, 48% of patients had a best overall response of stable disease, and the disease control rate was 85%. Twenty-eight patients remained on treatment at the data extract date.

The responses seen with RMC-6326 in patients with NSCLC are durable, and further follow-up data may show deepening of these responses over time, Arbour emphasizes. Moreover, the median time to response was 1.4 months (range, 1.2-2.7), indicating that this agent provided symptom relief for patients shortly after treatment initiation, Arbour concludes.

Editor’s Note: Dr Arbour reports consulting roles with Amgen, Novartis, G1 Therapeutics, AstraZeneca, and Sanofi-Genzyme; and institutional research funding from Genentech (local PI), Mirati Therapeutics (local PI), and Revolution Medicines (local PI).

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