FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC

Abstract

On May 28, 2021, the FDA granted accelerated approval to sotorasib (Lumakras, Amgen) for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with a Kirsten rat sarcoma proto-oncogene (KRAS) G12C mutation who have received at least one prior systemic therapy. The approval was based on CodeBreaK 100 (Study 20170543), a dose-escalation and dose-expansion trial in patients with an advanced, KRAS G12C-mutated, solid tumor. The overall response rate (ORR) observed in patients with KRAS G12C-mutated NSCLC treated with sotorasib (n = 124) was 36% [95% confidence interval (CI), 28-45]. The median duration of response was 10.0 months (95% CI, 6.9-not estimable). The most common adverse reactions (≥20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. This is the first approval of a targeted therapy for KRAS G12C-mutated NSCLC. Because of pharmacokinetic data and ORRs of patient cohorts who took sotorasib at lower doses in the dose-escalation portion of CodeBreaK 100, a dose comparison study is being conducted as a post-marketing requirement.

Figure 1.. Mean Sotorasib Multiple-Dose (Day 8) Plasma Concentration-Time Profiles Following Oral Administration of Sotorasib QD under Fasted Conditions in Patients with KRAS G12C-Mutated Advanced Solid Tumors.

Plasma was collected over time from patients with KRAS G12C mutated advanced solid tumor who were enrolled in CodeBreaK 100 and receiving sotorasib at 180mg, 360mg, 720mg, or 960mg. Plasma concentrations of sotorasib were measured over time. Data are represented as Mean and Standard Error. Source U.S. Food and Drug Administration. NDA Multi-disciplinary Review and Evaluation (NDA 214665) and Approval Package: LUMAKRAS (sotorasib) (ref 19).