WCLC 2020: Small-Molecule Inhibitor Active in KRAS G12C–Mutated NSCLC
Posted: Tuesday, February 2, 2021
In the international phase II CodeBreak 100 trial, the first-in-class small-molecule inhibitor sotorasib seemed to confer deep responses and durable clinical benefit in patients with pretreated locally advanced or metastatic KRAS G12C-mutated non–small cell lung cancer (NSCLC), according to Bob T. Li, MD, PhD, MPH, of the Memorial Sloan Kettering Cancer Center (MSK), New York, and colleagues. This primary analysis, which was presented at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer Singapore (WCLC; Abstract PS01.07), held in virtual format in January 2021, supports the previous phase I results.
“This is a historic milestone in lung cancer therapy,” Dr. Li commented in an MSK press release. “Further clinical trials of sotorasib, either alone or in combination with other cancer drugs, are under way in an effort to potentially benefit even more patients.”
A total of 126 patients were administered 960 mg of oral sotorasib once daily; of them, 123 had at least a single measurable lesion at baseline and were evaluated for efficacy. Follow-up data were provided for a median of 9.3 months. Confirmed responses occurred in 46 patients; the investigators reported 2 complete responses and 44 partial responses. The objective response rate was 37.4%. At a median follow-up of 6.9 months for duration of response, more than half of responders (52.2%) remained on treatment without disease progression. A disease control rate of 80.5% was reported. The median duration of progression-free survival was 6.7 months.
According to the investigators, 69.8% of patients experienced a treatment-related adverse event of any grade; as a result, 7.1% discontinued treatment. Treatment-related adverse events of grade 3 or higher occurred in 20.6% of patients. Alanine aminotransferase increase (6.3%), aspartate aminotransferase increase (5.6%), and diarrhea (4.0%) were reported most frequently. There were no treatment-related deaths.
Disclosure: For full disclosures of the study authors, visit wclc2020.iaslc.org.
