Sotorasib produced a “rapid and durable clinical benefit” in patients with previously treated, KRAS p.G12C-mutated non-small cell lung cancer (NSCLC), researchers reported in The New England Journal of Medicine.1
Sotorasib previously demonstrated efficacy in the phase 1 portion of the CodeBreaK100 trial (ClinicalTrials.gov Identifier: NCT03600883), which enrolled patients with advanced solid tumors.2
In the phase 2 portion of the trial, researchers evaluated sotorasib in patients with locally advanced or metastatic KRAS p.G12C-mutated NSCLC. The trial enrolled 126 patients, most of whom (81%) had previously received both platinum-based chemotherapy and PD-1/PD-L1 inhibitors.
The median duration of treatment with sotorasib was 5.5 months. A majority of patients (69.8%) received sotorasib for 3 months or more, 47.6% received it for 6 months or more, and 32.5% for 9 months or more.
The objective response rate was 37.1%, including a complete response rate of 3.2%. The median duration of response was 11.1 months. The disease control rate was 80.6%.
Responses were observed regardless of baseline PD-L1 expression levels, tumor mutational burden, and co-occurring mutations in STK11, KEAP1, or TP53.
The median progression-free survival was 6.8 months, and the median overall survival was 12.5 months.
Treatment-related adverse events (TRAEs) of any grade were observed in 69.8% of patients. Grade 3 TRAEs occurred in 19.8%. Grade 4 pneumonitis and dyspnea occurred in 1 patient.
The researchers noted that no new safety signals were identified during the study.
Disclosures: This research was supported by Amgen and the National Institutes of Health. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
- Skoulidis F, Li BT, Dy GK, et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med. 2021;384(25):2371-2381. doi:10.1056/NEJMoa2103695
- Hong DS, Fakih MG, Strickler JH, et al. KRASG12C inhibition with sotorasib in advanced solid tumors. N Engl J Med. 2020;383(13):1207-1217. doi:10.1056/NEJMoa1917239