Updated results from the phase 1a FIT-001 trial show that darlifarnib (KO-2806) combined with cabozantinib produced encouraging results in patients with advanced clear cell renal cell carcinoma (ccRCC) who had not previously received cabozantinib. The overall response rate ranged from 33% to 50% across the dose groups, and the median progression-free survival was 13 months. The median duration of response has not yet been reached, with more than half of the responding patients still receiving treatment.
Darlifarnib works by blocking RHEB farnesylation, which inhibits the mTORC1 pathway while preserving mTORC2 activity. This approach is designed to improve the effectiveness of cabozantinib without adding significant overlapping side effects.
The combination was generally well tolerated. The most notable side effect was neutropenia, which was managed with dose adjustments and supportive care. A phase 1b dose-optimization study is now enrolling patients to compare the combination with cabozantinib alone and determine the recommended dose for a planned phase 3 registration trial expected to begin in 2028.