The first drug to target a KRAS mutation in non-small cell lung cancer (NSCLC) has been recommended for approval in Europe.

At its November meeting, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) endorsed the novel oral therapy sotorasib (Lumykras). The indication is use in the treatment of adults with advanced NSCLC with a KRAS G12C mutation who have progressed after at least one prior line of systemic therapy.

Sotorasib is an inhibitor of KRAS G12C, an oncogenic driver of tumorigenesis. The drug blocks tumor cell signaling and survival, inhibits cell growth, and selectively promotes apoptosis in tumors harboring KRAS G12C, according to the CHMP.

KRAS mutations are the most common mutations in NSCLC tumors, but for a long time appeared to be resistant to drug therapy.  

The KRAS G12C mutation occurs in about 13% of NSCLC mutations.

When clinical data on sotorasib were presented at the 2020 World Conference on Lung Cancer, lung cancer experts greeted the results enthusiastically, as reported by Medscape Medical News at the time.

“This is a historic milestone in lung cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” Bob Li, MD, PhD, MPH, of Memorial Sloan Kettering Cancer Center in New York City, said at the time.

The drug was approved by the US Food and Drug Administration in May based on a study of 124 patients with locally advanced or metastatic KRAS G12C-mutated NSCLC with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy.

The FDA approval was based on an overall response rate of 36%, the study’s primary outcome. Of the patients who responded, 58% had a duration of response of 6 months or longer.

The EMA says its recommendation for approval is based on objective response rate and response duration data.

The most common side effects of sotorasib are diarrhea, nausea, fatigue, increased aspartate aminotransferase, and arthralgia said the CHMP.

Nick Mulcahy is an award-winning senior journalist for Medscape, focusing on oncology, and can be reached at [email protected] and on Twitter: @MulcahyNick

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