Divarasib

The FDA has pushed back its decision deadline to move Amgen’s KRAS inhibitor Lumakras into metastatic colorectal cancer to January, the company told Endpoints News . The regulator was supposed to decide Thursday whether to approve the drug in combination with Amgen’s EGFR drug Vectibix for chemorefractory metastatic colorectal cancer patients who have a KRAS G12C mutation. After Endpoints sent Amgen questions about the status of the review, the company said the new deadline for action is three months from now, on Jan. 17, 2025. Amgen said the delay was to “allow additional time for review of supplemental data recently submitted to the agency.” Lumakras is currently approved under the accelerated pathway for non-small cell lung cancer. Another KRAS inhibitor, Bristol Myers Squibb’s Krazati, is also approved under the accelerated pathway in both lung cancer and colorectal cancer. The colorectal market is a large one, though KRAS G12C mutations make up just 3% to 4% of metastatic cases. Cancers of the colon and rectum are projected to make up 8% of all new cancer diagnoses in 2024, according to the National Cancer Institute . That places those cancers just behind breast, prostate and lung cancers. The FDA cleared Bristol Myers’ Krazati for use with Eli Lilly’s Erbitux in June for previously treated locally advanced or metastatic colorectal cancer patients. Amgen applied for approval in metastatic colorectal cancer with results from the CodeBreaK 300 study, which showed that a 960 mg dose of the drug resulted in a 30.2% response rate. However, it didn’t improve overall survival, according to data presented in June , though Amgen said the study wasn’t powered to show a statistically significant improvement in survival. Lumakras was the first KRAS inhibitor to win regulatory approval in 2021. It marked a major medical breakthrough. Researchers have long known that KRAS mutations drive cancer, but hadn’t been able to treat them in a targeted fashion. The efficacy of the drugs, though, has been modest. In lung cancer, the FDA declined to convert Lumakras’ accelerated approval to a full one in December, citing concerns around the reliability of the pivotal trial data and noting that the median progression-free survival benefit could be less than what Amgen claimed — and potentially as little as five days. Commercially, sales of Lumakras have been tepid, generating $167 million for the first half of the year. Roche is developing its own KRAS inhibitor divarasib, which it is studying in a Phase 3 trial head-to-head against Krazati and Lumakras in second-line lung cancer and Phase 1/1b for colorectal cancer. Other companies, including Revolution Medicines, are developing RAS inhibitors that they hope can be more effective and go beyond the single mutation G12C, which could help treat more patients.