Phase 2 Trial for Sotorasib Yields Positive Results With Certain Type of NSCLC

October 10, 2020

In announcing the topline results, Amgen said that sotorasib met the primary end point of centrally assessed objective response rate.

Weeks after reporting positive results for a phase 1 trial, Amgen said that its KRAS p.G12C inhibitor, sotorasib (AMG 510), performed well in patients with non-small cell lung cancer (NSCLC) during a phase 2 trial.

The open-label multicenter trial, as part of the CodeBreaK 100 clinical study, evaluated sotorasib in 126 patients with KRAS p.G12C-mutant advanced NSCLC who were unsuccessful using a median of 2 prior anti-cancer therapies.

"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 Reese, MD, executive vice president of Research and Development at Amgen, said in a statement​.

According to Amgen, the KRAS p.G12C mutation occurs in 13% of NSCLC cases and in 3% to 5% of colorectal cancers and 1% to 2% of numerous other solid tumors. The KRAS protein is the most commonly altered gene mutation associated with solid tumors. Currently, there are no FDA-approved therapies for tumors with KRAS mutations.

In announcing the topline results, Amgen said that sotorasib met the primary end point of centrally assessed objective response rate, which was consistent with the results from the phase 1 trial that were previously published in the New England Journal of Medicine. More detailed results of the study will be submitted to the IASLC 2020 World Congress on Lung Cancer that will take place in January 2021.

Of the 126 patients enrolled, 123 had centrally evaluable lesions by RECIST at baseline

"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,” said Reese.

Reese said Amgen is looking to discuss the current results and next steps for sotorasib with the FDA and other regulatory agencies.

Amgen’s single-arm phase 2 trial, also a part of the CodeBreak 100 study, is fully enrolled and is evaluating sotorasib in patients with colorectal cancer. Amgen said that results of the trial are expected in 2021.

Amgen also said that the CodeBreaK 2020 global phase 3 randomized active-controlled confirmatory study has begun recruiting to compare the effects of sotorasib to docetaxel in patients with KRAS p.G12C-mutant NSCLC.

The company is conducting enrollment for several phase 1b combination studies across various advanced solid tumors as part of the CodeBreaK 101 study.