Preliminary results of the use of tipifarnib demonstrate encouraging activity in solid tumors with mutant HRAS

Phase II trials evaluated the activity of tipifarnib in squamous carcinomas, tumors of the thyroid and salivary glands, urothelial carcinomas, among others

HRAS is an overexpressed and mutated proto-oncogene in head and neck squamous carcinomas (HNSCC) and other squamous cell carcinomas (SCCs). HRAS mutations are seen in 6 to 10% of HNSCC cases. Tipifarnib is a potent and highly selective inhibitor of farnesyltransferase, an enzyme critical to the proper function of HRAS.

During the ASCO 2020 Virtual Annual Meeting, data was presented from two Phase II clinical trials. The studies investigated the activity of tipifarnib in solid tumors with mutant HRAS: KO-TIP-001 (squamous carcinomas [SCC], tumors of the thyroid and salivary glands, among others); IST-01 (urothelial carcinomas, UC).

Based on preliminary efficacy results, KO-TIP-001 was changed to continue enrolling only patients with head and neck SCC (HNSCC) (cohort 2) and other SCC patients (cohort 3) with tumors carrying a high frequency of allele variant mutant HRAS (VAF)> 20%.

Until the cutoff date, 21 patients with HNSCC had been treated with tipifarnib, of which 18 were assessed for effectiveness. Ten objective responses were observed (overall response rate 56%). The progression-free survival (PFS) of tipifarnib and the last therapy prior to the trial were 6.1 and 2.8 months, respectively. In addition, 13 patients with recurrent / metastatic salivary gland tumors (SGT) were treated in KO-TIP-001 or in extended access programs. An objective response was observed in 12 (8%) evaluable patients and an additional 7 (58%) presented stable disease as the best response. The median PFS of patients with SGT was 7 months.

In IST-01, 16 patients had mutations in HRAS and 15 were included in the trial. Five responses were observed in 12 patients with UC assessed (42%) and 3 additional patients had a reduction in tumor size. The median SLP was 5.1 months.

These studies have shown encouraging activity of tipifarnib in solid tumors with mutant HRAS.

References:
J Clin Oncol 38: 2020 (suppl; abstr 6504)
https://meetinglibrary.asco.org/record/185451/abstract