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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Monday, June 17, 2024
According to Timothy F. Burns, MD, PhD, of the University of Pittsburgh Medical Center Hillman Cancer Center, and colleagues, any-line treatment with certain dose levels of the second-generation KRAS G12C inhibitor olomorasib (LY3537982) plus the PD-1 inhibitor pembrolizumab appeared to be safe and active in patients with KRAS G12C–mutated advanced non–small cell lung cancer (NSCLC). These results from the phase I/II LOXO-RAS-20001 trial, which were presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 8510), support the ongoing evaluation of this combination in the first-line setting (SUNRAY-01; ClinicalTrials.gov identifier NCT06119581).
A total of 50 patients received 50 to 150 mg of oral olomorasib twice daily plus 200 mg of pembrolizumab once every 3 weeks. Dose escalation was performed using a modified toxicity probability interval method.
During the dose-escalation phase, liver function test abnormalities of grade 3 or higher were documented in two of the six patients who received 150 mg of olomorasib, precluding its further evaluation. Diarrhea (30%), increased alanine transaminase levels (20%), increased aspartate aminotransferase levels (18%), fatigue (14%), nausea (14%), and pruritus (11%) were the most frequently reported treatment-related adverse events in the 44 patients who received either 50 or 100 mg of olomorasib. The most common grade 3 treatment-related adverse event was diarrhea (16%). Three patients experienced pneumonitis (grades 2, 3, and 4).
Among the 30 efficacy-evaluable KRAS G12C inhibitor–naive patients, at a median follow-up of 6 months, the objective response rate was 63%, and the disease control rate was 93%. The median progression-free survival was not estimable. In patients whose tumors had a PD-L1 expression level of at least 50% (n = 12) or less than 50% or unknown (n = 18), the objective response rates were 75% and 56%, respectively. The objective response rate was 78% in those who were treated in the first-line setting (n = 9); the disease control rate was 100%.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
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