ASCO Plenary Series: Phase II Study of Glecirasib in KRAS G12C–Mutated NSCLC

By: Vanessa A. Carter, BS
Posted: Friday, May 3, 2024

Among patients with non–small cell lung cancer (NSCLC) in China, approximately 4% harbor a KRAS G12C mutation. During the American Society of Clinical Oncology (ASCO) Plenary Series: April 2024 Session (Abstract 468214), Yuankai Shi, MD, PhD, of the National Cancer Center and Cancer Hospital and the Chinese Academy of Medical Sciences and Peking Union Medical College, and colleagues presented their study results on the oral KRAS G12C inhibitor glecirasib in patients with NSCLC harboring a KRAS G12 mutation.

“The pivotal phase II study of glecirasib has met the primary endpoints and demonstrates impressive objective response rates and progression-free survival with promising clinical activity for patients with KRAS G12C–mutated advanced NSCLC,” the study authors concluded. “Glecirasib is well tolerated, with an extremely low gastrointestinal toxicity profile, which may improve patient compliance with oral therapy.”

This phase II, single-arm study enrolled 119 patients with locally advanced or metastatic NSCLC harboring a KRAS G12C mutation across 43 sites in China. Participants were administered 800 mg of glecirasib daily. Eligible patients underwent prior platinum-based therapy and an immune checkpoint inhibitor. The primary study endpoint was overall response rate, and secondary endpoints were progression-free survival, duration of response, disease control rate, and safety.

The median follow-up was 10.4 months, and the median patient age was 62 years. Although the median duration of response was not reached, the disease control rate was 86.3%, and the overall response rate was 47.9%. Median progression-free survival and overall survival were 8.2 months and 13.6 months, respectively.

Nearly all patients experienced a treatment-related adverse event (97.5%), with the most common being anemia (56.3%), increased bilirubin (48.7%), increased aspartate aminotransferase and alanine aminotransferase (35.3%), and hypertriglyceridemia (28.6%). Grade 3 and 4 events were reported in 39.5% of patients; no grade 5 events were observed. Of note, 5% of patients discontinued treatment because of a treatment-related adverse event.

Disclosure: The study authors reported no conflicts of interest.

ASCO Plenary Series: April 2024 Session