Amgen's sNDA for Lumakras (Sotorasib) Denied Full Approval by FDA for KRAS G12C-Mutated NSCLC

Dec 27, 2023 07:31 CST Updated 07:31

Amgen

Developer of Treatment Drugs for Serious Diseases

On December 26, Amgen announced that the FDA had completed the review of the new drug supplemental application for Lumakras (sotorasib) and refused to grant full approval for Lumakras to treat patients with KRAS G12C-mutated non-small cell lung cancer who have received at least one prior systemic therapy. The FDA requested that Amgen conduct additional confirmatory studies and complete them no later than February 2028.

Sotorasib, a KRAC G12C inhibitor developed by Amgen, received FDA Accelerated Approval (AA) in May 2021 based on the single-arm, multicenter, Phase I/II CodeBreak 100 study for patients with KRAS G12C-mutated non-small cell lung cancer who have previously received at least one systemic therapy.

CodeBreak 100 study results showed that, with a median follow-up of 15.3 months, among 124 evaluable patients, the ORR was 37.1% (3.2% being CR), the median DOR was 11.1 months, the median PFS was 6.8 months, and the median OS was 12.5 months. In terms of safety, 69.8% of patients experienced treatment-related adverse events (TRAEs), 19.8% (25 patients) had Grade 3 AEs, and 0.8% (1 patient) had Grade 4 AEs.

For verificationsotorasibAs part of the post-marketing requirement for clinical benefit, the sponsor conducted an open-label, randomized, multi-center, Phase III CodeBreaK 200 study, in which patients who had progressed after prior treatment with platinum-based chemotherapy and PD-1 or PD-L1 inhibitors were randomly assigned in a 1:1 ratio to receive either sotorasib (960 mg po qd) or docetaxel (75 mg/m² iv q3w).The primary endpoint was PFS assessed by BICR in the ITT population (imaging assessment at screening, then every 6 weeks up to Week 49, and every 9 weeks thereafter).

The study enrolled a total of 345 patients with a median follow-up of 17.7 months. The median PFS in the sotorasib group (n=171) and the docetaxel group (n=174) was 5.6 months and 4.5 months, respectively (HR=0.66, 95% CI 0.51-0.86, P=0.0017), reaching the primary endpoint. However, there was no significant difference in the key secondary endpoint OS (10.6 vs 11.3 months, HR=1.01, 95% CI 0.77-1.33, P=0.53).

In February 2023, based on the CodeBreaK 200 study, the sponsor submitted a supplemental New Drug Application to the FDA for sotorasib in patients with KRAS G12C-mutated NSCLC who had received at least one prior systemic therapy, seeking full approval. At the ODAC expert committee meeting held by the FDA in October this year, the final vote was 2 in favor and 10 against, concluding that the primary endpoint PFS of CodeBreaK 200 could not be reliably interpreted. (Recommended reading:ODAC Review: The Landscape of New Drug Development and Evidence-Based Summary for KRAS-Mutated Advanced Non-Small Cell Lung Cancer）

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