Amgen announced results from the Phase 2 cohort of the CodeBreaK 100 study evaluating sotorasib (AMG 510) in 126 patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC). The results will be presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 2020 World Conference on Lung Cancer (WCLC).
CodeBreak 100 is a phase 1/2 open-label multicenter study enrolling patients with KRAS G12C-mutant solid tumors. Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 portion of the study is centrally assessed objective response rate. The Phase 2 portion in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline. Patients were treated with sotorasib 960 mg once daily orally. Prior to the trial, 81% of patients had progressed on both platinum-based chemotherapy and PD1/L1 inhibitors, with the remainder progressing after having received one of these therapies. A separate cohort of patients with colorectal cancer (CRC) is fully enrolled and topline results are expected in 2021.
Sotorasib demonstrated a confirmed objective response rate (ORR) and disease control rate (DCR) of 37.1% and 80.6%, respectively, and a median duration of response of 10 months (data cutoff of Dec.1, 2020; median follow-up time was 12.2 months). The results also highlighted that sotorasib is the first KRASG12C inhibitor to show progression-free survival (median of 6.8 months) in a Phase 2 study. Over 80% of patients achieved disease control, including three complete responses and 43 partial responses, and the median best tumor shrinkage among all responders (n=46) was 60%. The median time to objective response was 1.4 months.
Sotorasib is a KRASG12C inhibitor. Sotorasib has demonstrated a positive benefit-risk profile with fast, deep and durable anticancer activity in patients with NSCLC harboring the KRAS G12C mutation with a once daily oral formulation. Breakthrough Therapy Designation has been granted in the U.S.