In an analysis published in the Journal of Clinical Oncology, Grace K. Dy, MD, and colleagues report 2-year outcomes of the CodeBreaK100 phase I/II trial of sotorasib in previously treated patients with KRAS G12C–mutated locally advanced or metastatic non–small cell lung cancer (NSCLC). According to the investigators, the 2-year analysis is, to their knowledge, the largest clinical data set with the longest follow-up reported for patients treated with any KRAS G12C inhibitor to date.
The trial supported the May 2021 accelerated approval of sotorasib for patients with KRAS G12C–mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy.
Grace K. Dy, MD
Study Details
In the multicenter trial, 174 patients received sotorasib at 960 mg once daily. Nearly all patients had stage IV disease. The median number of prior treatments was two, with 25% of patients having received three or more.
Key Findings
Median follow-up was 24.9 months (range = 0.7–35.9 months). The objective response rate was 41% (95% confidence interval [CI] = 33.3%–48.4%) and the disease control rate was 84% (95% CI = 77.3%–88.9%). Among patients with objective response, responses were ongoing at 6 months in 72.8% and 12 months in 50.6%.
Median duration of response was 12.3 months (95% CI = 7.1–15.0 months). At data cutoff, 9 (13%) of 70 patients who had responded remained on study without disease progression, including 5 who received sotorasib for 2 years or longer with continued response.
Median progression-free survival was 6.3 months (95% CI = 5.3–8.2 months). Median overall survival was 12.5 months (95% CI = 10.0–17.8 months). Estimated rates at 12 and 24 months were 51% (95% CI = 42.8%–58.2%) and 33% (95% CI = 25.0%–40.2%).
Among 172 efficacy-evaluable patients, 40 (23%) had long-term clinical benefit, defined as progression-free survival lasting at least 12 months. Long-term clinical benefit was observed across PD-Ll tumor proportion score (TPS; 16 of 31 patients with TPS < 1%, 6 of 12 with TPS 1%–49%, and 1 of 4 with TPS ≥ 50%); according to STK11 and KEAP1 somatic mutation status (6 of 13 with KEAP1 wild-type/STK11-mutant and 15 of 33 with KEAP1 wild-type/STK11 wild-type status, and 8 of 25 with STK11-mutant and 16 of 40 with STK11 wild-type status); and in association with lower baseline circulating tumor DNA levels (P = .01).
Among 45 patients who continued treatment with sotorasib beyond 1 year, 11 (24%) had any-grade adverse events after 1 year on treatment (new-onset), with no trend in adverse event types. One grade 3 event was observed (hemolytic anemia). No new-onset grade 4 or 5 adverse events were observed, and no new-onset events led to treatment discontinuation.
The investigators concluded, “These results demonstrate the long-term benefit of sotorasib, including in subgroups with poor prognosis.”
Dr. Dy, of Roswell Park Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Amgen Inc. For full disclosures of the study authors, visit ascopubs.org.
