Amgen’s Lumakras Study Results Show Long-Term Efficacy for Treatment of NSCLC

Sotorasib demonstrates clinical benefit and prolonged tumor response seen, with a 40.7% objective response rate.

Long-term efficacy and safety data from the CodeBreaK 100 phase 1/2 trial in individuals with KRAS G12C-mutated advanced non–small cell lung cancer (NSCLC) who took sotorasib (Lumakras) is positive, Amgen said in a statement.

The data of the 2-year follow up was presented as part of a clinical trials plenary session at the American Association for Cancer Research annual meeting.

Sotorasib is the first and only KRASG12C inhibitor to date that shows long-term clinical benefit and overall survival for individuals with NSCLC with the KRAS G12C mutation.

“With regulatory approvals in nearly 40 countries and thousands of patients treated, sotorasib, the only approved KRAS G12C inhibitor, is a transformative targeted therapy for the treatment of patients living with KRAS G12C-mutated NSCLC,” David Reese, MD, executive vice president of research and development at Amgen, said in a statement. “We are pleased with these latest results from the CodeBreaK 100 study, which represent the longest follow-up of patients treated with a KRASG12C inhibitor and confirm rapid, deep, and durable responses in patients receiving sotorasib.”

In the 2-year analysis, investigators included 174 individuals who were heavily pre-treated. Sotorasib showed a confirmed objective response rate (ORR) of 40.7%, a disease control rate of 83.7%, and a median duration of response (DOR) of 12.3 months.

Investigators reported that 5 individuals achieved complete responses, while 65 achieved partial responses. The results also showed a median progression-free survival of 6.3 months and overall survival of 12.5 months. Additionally, approximately 32.5% of individuals were still alive at the 2-year follow-up.

There were no new safety signals identified for sotorasib during the long-term follow-up.

The most common adverse events reported were cough, diarrhea, fatigue, hepatotoxicity, musculoskeletal pain, and nausea.

Additionally, it was reported that hepatotoxicity could lead to drug-induced liver injury and hepatitis.

Sotorasib could also cause interstitial lung disease or pneumonitis, which could be fatal, according to the statement,

“Since the FDA approval almost a year ago, sotorasib has changed the treatment paradigm for patients with advanced non-small cell lung cancer who harbor the KRAS G12C mutation,” Grace Dy, MD, chief of thoracic oncology at Roswell Park Comprehensive Cancer Center, said in the statement. “The durable efficacy and positive benefit-risk profile seen in the 2-year analysis of CodeBreaK 100 highlight the important role this innovative targeted therapy can offer long-term.”.

In May 2021, sotorasib became the first KRASG12C inhibitor to receive regulatory approval with its approval in the United States. It is now approved in 29 countries, including the European Union, Switzerland, and the United Kingdom.

The indication is approved under accelerated approval based on the DOR and ORR. Continued approval for the indication could be affected by verification and description of clinical benefit confirmed in trials.

Sotorasib is also being studied as treatment in multiple other solid tumors, according to the statement.

Reference

Lumakras (sotorasib) CodeBreaK 100 study shows two-year overall survival of 32.5% in patients with KRAS G12C-mutated advanced non–small cell lung cancer. Amgen. News release. April 10, 2022. Accessed April 12, 2022. https://www.amgen.com/newsroom/press-releases/2022/04/lumakras-sotorasib-codebreak-100-study-shows-twoyear-overall-survival-of-325-in-patients-with-kras-g12cmutated-advanced-nonsmall-cell-lung-cancer