NEW YORK – Amgen on Tuesday said that it received a complete response letter from the US Food and Drug Administration for converting the accelerated approval of Lumakras (sotorasib) as a treatment for patients with KRAS G12C-mutated non-small cell lung cancer to full approval.
In its response, the FDA said that Amgen had fulfilled the post-marketing requirement issued at the time it gave Lumakras accelerated approval to compare the safety and efficacy of a 960 mg daily dose to a lower dose. However, it issued a new post-marketing requirement for an additional confirmatory study to support full approval to be completed no later than February 2028. In an email, an Amgen spokesperson said the company is working with the FDA to confirm the details of the new study.
The FDA's accelerated approval of Lumakras was based on data from a single-arm Phase II trial in patients with locally advanced, unresectable, or metastatic NSCLC harboring KRAS G12C mutations who had received at least one prior systemic therapy. That approval came with a post-marketing requirement to confirm the benefits seen in that study and to conduct a dose optimization study. The agency based its latest decision on data from the confirmatory CodeBreaK 200 clinical trial in which Amgen compared the activity of Lumakras to docetaxel chemotherapy in that same setting.
In the CodeBreaK 200 trial, Amgen reported that median progression-free survival for patients on Lumakras was 5.6 months versus 4.5 months for those on docetaxel. However, in a meeting of the FDA's Oncologic Drugs Advisory Committee in October, advisers said they could not reliably interpret the progression-free survival data. The committee members noted patterns in patient dropouts, data censoring, and how investigators determined which patients experienced cancer progression that raised concerns about systemic bias in the trial.
Amgen also explored optimal dosing of Lumakras in the Phase I/II CodeBreaK 100 trial by comparing a 960 mg daily dose of Lumakras to a 240 mg daily dose in patients with advanced KRAS G12C-mutated NSCLC. In results reported at the European Society of Medical Oncology's annual meeting in November, Amgen reported an overall response rate of 32.7 percent for patients on 960 mg Lumakras and 24.8 percent for patients on the 240 mg dose. The disease control rates were 86.5 percent and 81.9. percent, respectively, and at a median follow-up of 17.5 months, the median overall survival was 13 months for patients on the 960 mg dose and 11.7 months for those on 240 mg. Amgen concluded that patients fared better on the 960 mg dose and that those results were backed up by data from the CodeBreaK 300 trial in which patients on the 960 mg dose showed a greater benefit than those on 240 mg.
"We remain confident in the value Lumakras offers patients worldwide based on the totality of data shared and real-world clinical experience and continue to advance the CodeBreaK clinical trial program," the Amgen spokesperson said. "All ongoing research of Lumakras in new combinations, lines of therapy, and tumor types will continue as planned."