Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer

Abstract

Sotorasib (LUMAKRAS™ in the USA and LUMYKRAS™ in the EU) is an orally active, first-in-class G12C-mutant KRAS (KRAS^G12C) inhibitor. By binding irreversibly to KRAS^G12C, sotorasib inhibits downstream signalling pathways which are associated with cell growth and differentiation. Sotorasib is indicated for the treatment of adults with advanced, previously treated, KRAS G12C mutation-positive non-small cell lung cancer (NSCLC) in multiple countries, including the countries of the EU and the USA. A clinically relevant objective response rate was observed in patients with KRAS G12C mutation-positive NSCLC during the primary analysis and in an updated analysis of the phase I/II CodeBreaK 100 trial. Furthermore, a clinically relevant response duration was reported in updated analyses of the trial. Sotorasib has a manageable tolerability profile, with permitted dose modifications to manage toxicity. In summary, sotorasib is a promising KRAS^G12C inhibitor that increases the available treatment options for patients with KRAS G12C mutation-positive NSCLC who were previously treated with platinum-based chemotherapy and/or immunotherapy.

Fig. 1

Trial design of the open-label phase I/II CodeBreaK 100 trial in adults with advanced, previously-treated, KRAS G12C mutation-positive solid tumours, including NSCLC [16, 17]. Efficacy results are reported in the animated figure (available online). KRAS Kirsten rat sarcoma virus, NSCLC non-small cell lung cancer. ^a123 patients with evaluable disease during the primary analysis; 124 patients during the updated analysis

Fig. 2

Treatment-related AEs with an incidence ≥ 5% of patients with locally advanced or metastatic non-small cell lung cancer enrolled in the phase II portion of CodeBreaK 100 (n = 126) [16]. AEs adverse events