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David S. Ettinger, MD, FACP, FCCP


WCLC 2022: Early Data on Sotorasib Plus an SHP2 Inhibitor in KRAS-Mutated NSCLC

By: Vanessa A. Carter, BS
Posted: Wednesday, August 24, 2022

During the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer (WCLC) 2022 (Abstract OA03.03), Gerald Falchook, MD, of Sarah Cannon Research Institute, Denver, presented early study results of the KRAS G12C inhibitor sotorasib in combination with the SHP2 inhibitor RMC-4630 in patients with KRAS G12C–mutated non–small cell lung cancer (NSCLC) and other solid tumors. Ultimately, the results of this study suggest this treatment combination was “safe and tolerable” in this patient population.

“Promising clinical activity was observed in KRAS G12C–mutated NSCLC patients, most notably in those KRAS G12C inhibitor–naive,” concluded David S. Hong, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues. “Dose expansion is underway to further define efficacy and safety in both KRAS G12C inhibitor–naive and KRAS G12C inhibitor–exposed NSCLC patients.”

This phase Ib study enrolled 21 patients with KRAS G12C–mutated NSCLC (n = 11) or other solid tumors (n =10). Participants were administered 960 mg of sotorasib daily, as well as RMC-4630 at escalating dose levels of 100 mg, 140 mg, or 200 mg.

The median number of prior therapy lines was two, and 10 patients underwent previous KRAS G12C inhibitor therapy. Of note, dose escalation was successfully carried out without any grade 4 or higher treatment-related adverse events. Moreover, treatment-related adverse events affected 71% of participants; three individuals discontinued treatment because of treatment-related adverse events.

A confirmed partial response was observed in three patients with NSCLC, and seven experienced disease control. Furthermore, three patients who were KRAS G12C inhibitor–naive achieved a partial response, and four had disease control; one individual who experienced disease progression achieved a partial response at 24 weeks but experienced further disease progression at 30 weeks. Of note, pharmacokinetics confirmed that RMC-4630 and sotorasib exposures were consistent with previous studies, and no significant drug-drug interactions were observed.

Disclosure: For full disclosures of the study authors, visit

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