Trial Results Show Sotorasib Is First, Only KRAS G12C Inhibitor With Overall Survival Data for Non-small Cell Lung Cancer


Phase 2 clinical trial results assessing sotorasib in previously treated patients with NSCLC showed that the drug presented a median OS of 12.5 months among 124 patients.

Results from the phase 2 CodeBreaK 100 clinical trial assessing sotorasib (Lumakras; Amgen) in previously treated patients with non-small cell lung cancer (NSCLC) showed that the drug presented a median overall survival (OS) of 12.5 months among 124 patients who were evaluable during the trial.

The findings, presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, focused primarily on data pertaining to OS, which was a secondary endpoint of the trial. The majority of patients in the trial had been treated with platinum-based chemotherapy and immunotherapy (81%) prior to commencement.

Additionally, the results confirmed sotorasib had an objective response rate (ORR) of 37.1%, duration of response (DoR) of 11.1 months, and disease control rate (DCR) of 80.6%. An additional patient was also able to achieve complete response, which brought the total to 4 complete responses and 42 partial responses compared to results that were previously reported.

The data presented at the 2021 ASCO Annual Meeting are updated from the previously presented results at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer in January 2021. These updated data are based on a longer follow-up time of 15.3 months.

"Patients with KRAS G12C-mutated non-small cell lung cancer face poor outcomes so we are pleased with these overall survival results and the impact LUMAKRAS may have for patients with this devastating mutation," said David M. Reese, MD, executive vice president of Research and Development at Amgen, in a press release. "The results further confirm the deep and durable responses we have seen with LUMAKRAS throughout the CodeBreaK clinical trial program, the most advanced KRAS G12C clinical trial program with the longest follow-up."

During the exploratory analyses, investigators observed that tumor response to sotorasib was consistent across multiple biomarker subgroups, such as patient subgroups stratified by baseline PD-L1 expression levels and those with STK11 mutation.

Within the patient subgroup separated by baseline programmed death-ligand 1 (PD-L1) expression (n=86), investigators observed that the tumor response and shrinkage were present across a range of baseline PD-L1 expression levels, with a response rate of 48% within the PD-L1 negative patient group (TPS <1%).

Furthermore, in the STK11 mutation group, the investigators observed an improved efficacy upon treatment of sotorasib with the concurrent wild-type KEAP1 (n=22), with an observed median progression free survival of 11.0 months and median OS of 15.3 months among this patient population.

"Sotorasib is the first KRASG12C inhibitor to show an overall survival benefit, and the data represent a major step forward for patients with KRAS G12C-mutated non-small cell lung cancer where standard of care options are suboptimal," said lead investigator Ferdinandos Skoulidis, MD, PhD, assistant professor of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center, in the press release. "KRAS has been one of the most challenging therapeutic targets in cancer research, and these practice-changing results give hope to patients with the KRAS G12C mutation who previously had no targeted treatment options."

On May 28, 2021, sotorasib received FDA approval for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy. Sotorasib also received an accelerated approval based on the positive ORR and DoR results, although the continued approval for this indication may require further verification and description of clinical benefit in a subsequent confirmatory trial.


Results From Phase 2 CodeBreaK 100 Show LUMAKRAS™ (sotorasib) Is The First And Only KRAS G12C Inhibitor With Overall Survival Data. Thousand Oaks, CA: Amgen; June 4, 2021. Accessed June 16, 2021.

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