Darlifarnib

At ESMO 2025, Kura Oncology presented early data on farnesyl transferase inhibitors (FTIs) darlifarnib and tipifarnib. Darlifarnib monotherapy showed on-target activity in HRAS-mutant tumors. Darlifarnib combined with cabozantinib yielded a 33-50% ORR in renal cell carcinoma. Tipifarnib with alpelisib achieved a 47% ORR in heavily pretreated PIK3CA-altered head and neck cancer. These preliminary results suggest FTIs can enhance targeted therapies by addressing resistance mechanisms. Further studies are ongoing to determine optimal dosing and durability.