lung cancer

Sotorasib for Lung Cancers with KRAS p.G12C Mutation

Sotorasib for Lung Cancers with KRAS p.G12C Mutation

Background and purpose

Sotorasib is a small molecule inhibitor of KRAS, and it has shown anticancer activity in patients with KRAS p.G12C mutated advanced solid tumors and phase 1 studies.  There is promising anticancer activity in the subgroup of patients with non-small cell lung cancer.


A single group, phase 2 trial, was developed to investigate the activity of Sotorasib in this subset of patients.  It was dosed at 960 mg once daily.  Patients with non-small cell lung cancer, with previous treatment exposure, were enrolled in the study.  The primary endpoint was objective response (partial or complete response).  Key secondary endpoints included duration of response, disease control (defined as stable disease, partial response, complete response) as well as progression free survival, overall survival and importantly safety.  Exploratory biomarkers were also evaluated.


126 patients were enrolled.  The majority, 81%, had previously received both platinum-based chemotherapy and inhibitors of PD1 or PD-L1.  According to central review, 124 patients have measurable disease at baseline and were evaluated for response.  An objective response was observed in 46 patients, 37.1%, 95% confidence interval, 28.6–46.2 including 4 patients, 3.2%, who had a complete response and 42 (33.9%) patients who had a partial response.  The median duration of response was 11.1 months.  Disease control occurred in 80.6% of patients, 100 patients.  The median progression free survival was 6.8 months, 95% confidence interval, 5.1–8.2, and the median overall survival was 12.5 months, 95% confidence interval, 10.0–could not be evaluated.  Treatment-related adverse events occurred in 69.8% of patients, 88–126 patients.  Great 3 adverse events occurred in 25 patients, 19.8% and a single grade 4 event occurred in 1 patient.  Responses were observed and subgroups defined according to PD-L1 expression as well as tumor mutation burden, and concurrence of other mutations including STK 11, 8 KE AP 1, or TP53.


The authors concluded “Sotorasib therapy led to a durable clinical benefit without safety signals in patients with previously treated KRAS p.G12C mutated non-small cell lung cancer.”


Sotorasib for Lung Cancers with KRAS p.G12C Mutation