Amgen's KRAS Inhibitor Lumakras Moves Closer to Full FDA Approval for Non-Small Cell Lung Cancer

▎Edited by the WuXi AppTec content team

Recently, Amgen announced that the FDA’s Oncologic Drugs Advisory Committee (ODAC) will review clinical trial data supporting the conversion of the accelerated approval for the KRAS inhibitor Lumakras (sotorasib) into a full approval. The committee meeting is scheduled for October 5 this year. Lumakras has already received accelerated approval for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation who have been previously treated.

KRAS gene mutation is one of the most common oncogenic gene mutations in cancer patients, and it was once famously considered an "undruggable" target. In May 2021, based on the response rate results from the open-label Phase 1/2 clinical trial CodeBreaK 100, the U.S. FDA granted accelerated approval for Lumakras. This represents a significant milestone in the development of drugs targeting KRAS.FDA's accelerated approval means that Amgen needs to conduct follow-up clinical trials to confirm the efficacy of Lumakras.

In September last year, Amgen announced the results of the Phase 3 clinical trial CodeBreaK 200.Compared with standard chemotherapy, Lumakras reduced the risk of disease progression or death by 34% (HR: 0.66, [95% CI: 0.51, 0.86]; P=0.002).After one year of treatment, the progression-free survival rate was 25% in the Lumakras group and 10% in the chemotherapy group. Additionally,Lumakras also met the secondary endpoint of objective response rate (ORR). The ORR in the Lumakras group was 28%, compared to 13% in the chemotherapy group (P

Lumakras simultaneously improved the disease control rate (83% vs. 60%).

Based on these data, Amgen has submitted a supplemental New Drug Application (sNDA) to convert the accelerated approval of Lumakras into a full approval. The FDA is expected to make a decision by December 24 this year.

[1] AMGEN TO DISCUSS APPLICATION FOR LUMAKRAS® (SOTORASIB) FOR THE TREATMENT OF KRAS G12C-POSITIVE NSCLC AT FDA ADVISORY COMMITTEE MEETING. Retrieved August 22, 2023, from https://www.amgen.com/newsroom/press-releases/2023/08/amgen-to-discuss-application-for-lumakras-sotorasib-for-the-treatment-of-kras-g12cpositive-nsclc-at-fda-advisory-committee-meeting