The FDA has granted accelerated approval to Bristol-Myers Squibb's Krazati (adagrasib) in combination with Eli Lilly's Erbitux (cetuximab) for the treatment of patients with KRAS G12C-mutated locally advanced or metastatic colorectal cancer (CRC) who have previously received chemotherapy. This decision marks a significant step forward in addressing a critical unmet need in CRC, where the KRAS G12C mutation occurs in approximately 3% to 4% of cases.
Clinical Efficacy and Trial Data
The approval is based on data from the Phase 1/2 KRYSTAL-1 study, which evaluated the efficacy and safety of Krazati in combination with cetuximab. The study demonstrated an overall response rate (ORR) of 34% and a median duration of response of 5.8 months. These findings provide a clinically meaningful benefit for patients with this specific KRAS mutation who have limited treatment options after prior chemotherapy.
Competitive Landscape and Market Potential
Krazati now competes with Amgen's Lumakras (sotorasib) in the KRAS inhibitor market. While both drugs are approved as second-line monotherapies for KRAS G12C-mutated non-small cell lung cancer (NSCLC), this new indication gives Krazati an opportunity to expand its market share. Amgen has also reported positive pivotal trial results in KRAS G12C-mutated colorectal cancer for Lumakras in combination with its own EGFR drug Vectibix (panitumumab).
According to GlobalData, the market for KRAS-targeting drugs in oncology could reach $4 billion by 2029, with Lumakras and Krazati accounting for a significant portion of that total. Morningstar analyst Damien Conover suggested that Krazati could become a $1 billion product following this CRC approval, justifying BMS’s acquisition of Mirati Therapeutics.
Ongoing Studies and Future Directions
The FDA's accelerated approval is contingent upon the results of a confirmatory trial. BMS has reported positive results from its confirmatory study in NSCLC, showing a significant improvement in progression-free survival (PFS). The company is also exploring Krazati in combination with Merck & Co's PD-1 inhibitor Keytruda (pembrolizumab) as a potential first-line NSCLC therapy.
KRAS Mutations in CRC
KRAS is one of the most frequently mutated oncogenes in human cancer and drives the disease in up to 50% of patients with CRC, according to BMS. The KRAS G12C mutation is a specific subtype that has become a focus of targeted therapy development. This approval represents a significant advancement in precision medicine for CRC patients with this mutation.
