Sotorasib Superiority Vs Standard of Care Docetaxel in Previously Treated KRAS G12C–Mutant NSCLC

Treatment with sotorasib (Lumakras) resulted in statistically significant superior progression-free survival (PFS) vs standard of care intravenous docetaxel in patients with previously treated KRAS G12C–mutant non–small cell lung cancer (NSCLC), according to topline findings from the phase 3 CodeBreak 200 trial (NCT04303780).¹

Investigators noted that the study met its primary end point of PFS. This is the first clinical trial to assess the safety and efficacy of sotorasib in a population of patients with KRAS G12C-mutated NSCLC who have been previously treated with a platinum-based doublet chemotherapy and a checkpoint inhibitor. Findings from the study are set to read out at an upcoming medical meeting.

“Further analyses of the data are ongoing, and we look forward to sharing detailed data at an upcoming medical meeting,” David M. Reese, MD, executive vice president of Research and Development at Amgen, said in a press release. "We are grateful to all of the investigators and patients who participated in this first randomized, controlled clinical trial of a KRAS G12Cinhibitor."

The randomized, active control trial enrolled a total of 345 patients. Patients received either sotorasib or docetaxel for 21-day cycles. Secondary end points for the trial included overall survival, objective response rate, patient-reported outcomes, quality of life, duration of response, time to response, disease control rate, and safety.

To enroll on the trial, patients were required to be 18 years or older with an ECOG performance status of 0 or 1. Pathologically documented, previously treated locally advanced and unresectable/metastatic disease with a KRAS G12C mutation confirmed via central testing or documentation was required before enrolling. Those with active brain metastases, myocardial infarction within 6 months of day 1 of the study, and gastrointestinal tract disease inhibiting the ability to inject oral medication were not able to enroll.

In May 2021, sotorasib was granted an accelerated approval by the FDA for patients with KRAS G12C–mutated NSCLC who have been treated with a minimum of 1 prior therapy.² The regulatory organization’s decision was based on data from the phase 1/2 CodeBreaK 100 clinical trial (NCT03600883), which highlighted deep, durable responses following treatment with sotorasib. In the population of 124 patients, the objective response rate was 36% (95% CI, 28%-45%), and the median duration of response was 10 months.

References

1. Amgen announces topline data from LUMAKRAS® (sotorasib) phase 3 trial in non-small cell lung cancer. News release. Amgen. August 30, 2022. Accessed August 31, 2022. https://bit.ly/3B274Vq
2. FDA approves first targeted therapy for lung cancer mutation previously considered resistant to drug therapy. News release. FDA. May 28, 2021. Accessed August 31, 2022. https://bit.ly/3fwHwVG