NEW YORK – The US Food and Drug Administration on Friday approved Amgen's sotorasib (Lumakras) for previously treated, locally advanced, or metastatic non-small cell lung cancer patients whose tumors harbor a KRAS G12C mutation.
The FDA also approved two companion diagnostics with sotorasib to identify patients with the KRAS G12C mutation: Qiagen's Therascreen KRAS RGQ PCR kit and Guardant Health's Guardant360 CDx. Qiagen's PCR test analyzes tumor tissue, and Guardant's next-generation sequencing test detects mutations in plasma samples.
Amgen partnered with Guardant and Qiagen last year to develop both the tissue- and blood-based companion diagnostics to identify patients with the KRAS G12C mutation. The FDA said if Guardant's test doesn't detect the mutation in patients' blood sample, then physicians should screen patients' tumor tissue for the mutation using Qiagen's test.
Sotorasib's approval makes it the first inhibitor of KRAS, once thought to be an "undruggable" target, to reach the market.
"The FDA approval of Lumakras is a breakthrough moment for patients with KRAS G12C-mutated non-small cell lung cancer because there is now a targeted therapy for this common, but previously elusive, mutation," David Reese, executive VP of R&D at Amgen, said in a statement. "The Lumakras development program was a race against cancer for Amgen's scientists and clinical trial investigators who together have now successfully delivered this new medicine to patients in less than three years — from first patient dosed to US regulatory approval."
The agency made its decision after evaluating data from the Phase II CodeBreak-100 clinical trial, which included 124 patients with locally advanced or metastatic, KRAS G12C-mutated NSCLC whose disease had progressed after receiving an immune checkpoint inhibitor or platinum-based chemotherapy. The objective response rate was 36 percent, and the disease control rate was 81 percent. Just over half (58 percent) of the responding patients continued to respond to the drug for six months or longer.
The FDA granted accelerated approval to sotorasib, and as such, Amgen may need to submit additional data to verify the clinical benefit seen in earlier studies. Specifically, the FDA has required a post-marketing study to investigate whether patients' responses to sotorasib are impacted by a lower dose.
Mirati Theapeutics is also advancing a registration-enabling study for adagrasib in KRAS G12C-mutated NSCLC and is expecting to complete a new drug application submission later this year. In a statement, the company highlighted that adagrasib is designed to sustain its inhibition of KRAS G12C, a potentially important attribute in treating KRAS G12C-mutated cancers, which regenerate every 24 to 48 hours.