Darlifarnib (KO-2806) Monotherapy in HRAS-Mutant Solid Tumors - Darlifarnib (KO-2806) is a next-generation FTI with enhanced potency and optimized PK properties[18] - In the FIT-001 monotherapy study, encouraging anti-tumor activity was observed in HRAS-mutant solid tumors[25] - One patient with HRAS-mutant salivary gland carcinoma showed a 62.8% tumor shrinkage from baseline after 80 weeks on 5 mg KO-2806[28, 30] - A patient with advanced HRAS-mutant HNSCC showed a 60% tumor shrinkage at week 8 on 8 mg KO-2806[32, 35] Darlifarnib + Cabozantinib Combination in Renal Cell Carcinoma (RCC) - The combination of KO-2806 and cabozantinib demonstrated a manageable safety profile in RCC patients[48, 69] - In ccRCC patients, the ORR ranged from 33% to 50%, and the DCR ranged from 80% to 100%[50, 69] - One patient with ccRCC treated with KO-2806 5 mg + cabozantinib 60 mg showed a 44% reduction in tumor size at week 16[57, 60] - In ccRCC patients with prior cabozantinib exposure, ORR ranged from 17% to 50%[50, 69] Tipifarnib + Alpelisib Combination in HNSCC - The combination of tipifarnib and alpelisib was well-tolerated in PIK3CA-mutant R/M HNSCC patients[79, 91] - An ORR of 47% was observed at a dose of tipifarnib 1200 mg/day + alpelisib 250 mg/day[80, 81, 91] - One patient with PIK3CA R88Q mutation achieved PR with 81% reduction at week 4[85, 88]