Darlifarnib — Investigational Agent
Other · Phase 1 · Kura Oncology
Mechanism of Action
Next-generation, oral farnesyl transferase inhibitor (FTI) that selectively blocks the enzyme farnesyltransferase, preventing post-translational farnesylation (prenylation) of RAS family proteins and RHEB (Ras homolog enriched in brain). Farnesylation is required for RHEB to localize to the lysosomal membrane and activate mTOR complex 1 (mTORC1). By inhibiting RHEB farnesylation, darlifarnib suppresses RHEB-dependent mTORC1 signaling — a critical adaptive resistance node that tumor cells co-opt to escape VEGFR tyrosine kinase inhibitors, KRAS inhibitors, and PI3Kα inhibitors. Unlike…
Investigational Indications
- Advanced clear cell renal cell carcinoma (ccRCC) — in combination with cabozantinib (VEGFR/MET/AXL TKI), including cabozantinib-naïve and cabozantinib-pretreated populations
- KRAS G12C-mutant advanced non-small cell lung cancer (NSCLC) — in combination with adagrasib, including patients with prior KRAS inhibitor exposure
- KRAS G12C-mutant advanced pancreatic ductal adenocarcinoma (PDAC) — in combination with adagrasib
- KRAS G12C-mutant advanced colorectal cancer (CRC) — in combination with adagrasib
- RAS-altered advanced solid tumors — monotherapy dose escalation cohort