The FDA has delayed its decision regarding the supplemental new drug application (sNDA) for sotorasib (Lumakras) in combination with panitumumab (Vectibix) for the treatment of patients with chemorefractory metastatic colorectal cancer (CRC) harboring a KRAS G12C mutation. The new target action date is set for January 17, 2025.
Amgen, the sNDA sponsor, stated that the extension allows the FDA to thoroughly review recently submitted supplemental information. The initial decision date was October 17, 2024.
CodeBreaK 300 Trial Data
The sNDA is based on data from the phase 3 CodeBreaK 300 study. The trial evaluated sotorasib in combination with panitumumab in patients with KRAS G12C-mutated metastatic CRC who had progressed on prior lines of chemotherapy. Results presented at the 2023 ESMO Congress demonstrated a median progression-free survival (PFS) of 5.6 months (HR, 0.49; 95% CI; 0.30-0.80) for patients receiving sotorasib 960 mg plus panitumumab, and 3.9 months (HR, 0.58; 95% CI, 0.36-0.93) for those receiving sotorasib 240 mg plus panitumumab. In comparison, patients treated with investigator's choice of trifluridine and tipiracil or regorafenib had a median PFS of 2.2 months (95% CI, 1.9-3.9).
Updated findings presented at the 2024 ASCO Annual Meeting indicated a trend toward improved overall survival (OS) in patients treated with the 960-mg dose of sotorasib plus panitumumab, although the study was not statistically powered to detect a significant difference. The median OS was not reached in the sotorasib 960 mg arm, 11.9 months (95% CI, 7.5-NE) in the sotorasib 240 mg arm, and 10.3 months (range, 7.0-NE) in the investigator’s choice arm. The hazard ratio for OS was 0.70 (95% CI, 0.41-1.18) with sotorasib 960 mg plus panitumumab compared with investigator’s choice, and 0.83 (95% CI, 0.49-1.39) with sotorasib 240 mg plus panitumumab compared with investigator’s choice.
Sotorasib's Prior Approvals and Setbacks
Sotorasib received accelerated approval from the FDA in May 2021 for treating locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC) after at least one prior line of therapy. This approval was based on data from the phase 2 CodeBreaK 100 study.
However, in December 2023, the FDA issued a complete response letter to the sNDA for sotorasib, which sought to convert the accelerated approval in NSCLC to a traditional approval. This followed an October 2023 Oncologic Drug Advisory Committee meeting where the panel voted that PFS data from the CodeBreaK 200 trial could not be reliably interpreted.
