Phase 2 CodeBreaK 100 Study Yields Positive Topline Results in Advanced NSCLC

The study is evaluating sotorasib in 126 patients with KRAS G12C-mutant advanced non-small cell lung cancer who had failed a median of 2 prior lines of anti-cancer therapies.

The phase 2 CodeBreaK 100 clinical study, evaluating sotorasib in 126 patients with KRAS G12C-mutant advanced non-small cell lung cancer (NSCLC) who had failed a median of 2 prior lines of anti-cancer therapies, demonstrated positive topline results, according to Amgen, the developer of the agent.

The first-in-human, open-label, multicenter study enrolled patients with KRAS G12C-mutant solid tumors. Patients included in the study must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease.

The primary end point for the phase 2 study was centrally assessed objective response rate (ORR). Of the 126 patients enrolled in the study, 123 had centrally evaluable lesions by RECIST at baseline.

Sotorasib demonstrated an ORR consistent with previously reported phase 1 data in patients with advanced NSCLC who were administered a 960 mg daily dose. Key secondary end points, including duration of response, were found to be promising as well and over half of the responders remained on treatment and continued to respond as of the cutoff date.

In addition, safety and tolerability were also similar to previously reported data in phase 1 in patients with advanced NSCLC.

“Targeting KRAS has been a 40-year quest that has left patients with limited options. These topline data underscore our belief in the potential for sotorasib to become the standard of care for non-small cell lung cancer patients with the KRAS G12C mutation who remain in need of new treatment options," David M. Reese, MD, executive vice president of Research and Development at Amgen, said in a press release.

"We now have more than 500 patients who have been enrolled across clinical studies, and we are rapidly moving forward with a broad-based development program, which includes monotherapy studies in non-small cell lung cancer, colorectal cancer and other solid tumors harboring the KRAS G12C mutation, as well as a suite of combination studies,” Reese continued. “We look forward to discussing the current results with the U.S. Food and Drug Administration and other regulatory agencies, to determine the best path forward for sotorasib as a potential treatment for patients with NSCLC harboring the KRAS G12C mutation."

Results from this potentially registrational phase 2 clinical trial in patients with advanced NSCLC are being submitted to the International Association for the Study of Lung Cancer (IASLC) 2020 World Congress on Lung Cancer, taking place in January 2021.

A global, phase 3, randomized, active-controlled, confirmatory study which will compare sotorasib to docetaxel in patients with KRAS G12C-mutant NSCLC, titled CodeBreaK 200, has already begun recruiting. Additionally, a single-arm phase 2 trial in colorectal cancer, which is also a part of CodeBreaK 100, is fully enrolled and topline results are anticipated in 2021. Amgen is also enrolling several phase 1b combination studies across various advanced solid tumors in CodeBreaK 101.


Amgen Announces Positive Topline Phase 2 Results For Investigational KRAS G12C Inhibitor Sotorasib In Advanced Non-Small Cell Lung Cancer [news release]. Thousand Oaks, California. Published October 5, 2020. Accessed October 5, 2020.