The KRAS p.G12C mutation is known to occur in 13% of non-small cell lung cancers (NSCLC) and 3% in colorectal cancers. However, there are no approved therapies for the treatment of KRAS mutations in cancer. This study aims to evaluate the efficacy of sotorasib, a small molecule that targets (irreversibly and selectively) KRASG12C.

This phase 1 trial included a total of 129 patients with advanced solid tumors with KRAS p.G12C mutation. The patients were assigned to receive sotorasib once daily. The primary outcome of the study was the overall safety of the treatment, along with pharmacokinetics and objective response.

The findings suggested that no dose-limiting or toxic effects were observed. A total of 73 patients experienced treatment-related adverse events, 11.6% of them being of grade 3 or 4. Among patients in the NSCLC subgroup, 32.2% of patients had a confirmed objective response rate, and 88.1% had disease control. The study further confirmed that the median progression-free survival was 6.3 months. In the colorectal cancer subgroup, the confirmed response rate was 7.1%, and the disease control rate was 73.8%.

The research concluded that sotorasib treatment for advanced solid tumors with KRAS p.G12C mutation was associated with promising anticancer activity.