Tipifarnib — Investigational Agent
Other · Phase 2/3 · Kura Oncology
Mechanism of Action
First-generation oral farnesyl transferase inhibitor (FTI) that competitively blocks the enzyme farnesyltransferase, preventing post-translational farnesylation of RAS family proteins. The critical mechanistic distinction between tipifarnib and later-generation FTIs is its preferential efficacy in HRAS-mutant tumors: unlike KRAS and NRAS, which can escape farnesyltransferase inhibition through alternative geranylgeranylation (a parallel prenylation route), HRAS depends exclusively on farnesylation for membrane anchoring and oncogenic signaling. When farnesyltransferase is inhibited,…
Investigational Indications
- HRAS-mutant recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) — monotherapy in patients with high HRAS variant allele frequency (VAF ≥20%) whose disease has progressed after prior therapy
- HRAS-mutant recurrent or metastatic HNSCC — in combination with alpelisib (PI3Kα inhibitor) in a registration-enabling study