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AACR 2026 | Elisrasib shows durable activity in pretreated KRAS G12C-mutant NSCLC

Byoung Chul Cho, MD, PhD, Yonsei University, Seoul, South Korea, discusses updated results from the Phase I/II trial (NCT05410145) of elisrasib monotherapy in previously treated KRAS G12C-mutant non-small cell lung cancer (NSCLC), including patients naïve or refractory to prior KRAS G12C inhibitors. Elisrasib demonstrated a favorable safety profile and durable antitumor activity across both groups, with particularly strong responses in inhibitor-naïve disease. This interview took place at the American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego, CA.

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Transcript

Elisrasib is a next-generation KRAS-G12C inhibitor designed to maximize target engagement and outpace growth factor, a stimulated GDP and GTP exchange. So in our phase one or two study, we enrolled patients with locally advanced or metastatic KRAS G12C mutant solid tumors. And in phase two expansion cohort, we enrolled both G12C inhibitor naive and refractory NSCLC population...

Elisrasib is a next-generation KRAS-G12C inhibitor designed to maximize target engagement and outpace growth factor, a stimulated GDP and GTP exchange. So in our phase one or two study, we enrolled patients with locally advanced or metastatic KRAS G12C mutant solid tumors. And in phase two expansion cohort, we enrolled both G12C inhibitor naive and refractory NSCLC population. So in our study, we observed a confirmed objective response rate of 52% and disease control rate nearly 100% in 600 milligram QD, of which was the RP2D. This was the confirmed objective response rate in G12C inhibitor naïve patient population. Regarding duration of response at 600 milligram QD, the median duration of response was 16.5 months, and median PFS was 12.2 months. When it comes to efficacy in G12C inhibitor refractory population, response rate was 32% in G12C-inhibitor refractory NSCLC population. And then median duration of response and median PFS in this refractory population was 15.6 months and 8.1 months, respectively. We showed an objective response rate of 30%, which was durable in refractory population, at least ELIS-RASIP may be a potential therapeutic option in patients who progress to a prior G12C inhibitor such as sotorasib or other KRAS inhibitors. More importantly, because elisrasib showed very potent efficacy in the G12C inhibitor naïve setting, which was far more potent than those from sotorasib or the first generation G12C inhibitors. I believe at least ELIS-RASIP is one of the best options in the G12C inhibitor naive setting. And among all other next-generation G12C inhibitors, ELIS-RASIP showed high efficacy with a very good safety profile.

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