According to results from the phase 2 AIN-HN study, tipifarnib demonstrated anti-tumor activity in later-line settings among patients with HRAS-mutated recurrent or metastatic head and neck squamous cell carcinoma who had received prior immunotherapy.

These results were presented at the European Society for Medical Oncology Congress in Madrid, Spain, by lead author, Alan L. Ho, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York.

“Despite recent advances, prognosis for [recurrent or metastatic head and neck squamous cell carcinoma] patients remains poor,” stated Dr Ho and coauthors. “Tipifarnib has activity in [patients] with [head and neck squamous cell carcinoma] harboring high variant allele frequency (VAF, ≥20%) mHRAS.”

In this study, 59 patients with histologically confirmed recurrent or metastatic head and neck squamous cell carcinoma who had previously had ≥1 platinum-containing regimen were eligible. Patients received 600 mg tipifarnib twice daily on days 1 to 7 and days 15 to 21 of a 28-day treatment cycle. There were 50 patients with high VAF and 26 who had received prior immunotherapy in the first-line. The primary end point was objective response rate (ORR) among patients with a high VAF (n = 50), as assessed by independent review facility (IRF). Patients who received ≥ 1 line of a platinum-containing regimen were additionally eligible for study enrollment.

At the data cut off point, the investigator-assessed ORR was 30% with 1 complete response. The IRF-assessed ORR was 20% with 1 complete response. Median progression-free survival (PFS) as assessed by IRF was 2.6 months and median overall survival (OS) was 7 months.

Grade ≥ 3 treatment-related adverse events occurred in 33 patients, with 7% of patients discontinuing treatment due to an adverse event. The most frequent events included neutropenia (24%), anemia (20%), leukopenia (14%), and febrile neutropenia (7%). 

“Tipifarnib is the first targeted therapy for this rare [head and neck squamous cell carcinoma] subset,” concluded Dr Ho et al. “Ongoing combination studies are targeting adaptive resistance pathways (PI3K/mTOR/Akt) to further improve outcomes.”

Source: 

Ho AL, Adkins DR, Hanna GJ, et al. A phase II study evaluating tipifarnib in mHRAS, recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (AIM-HN study). Presented at the 2023 ESMO Congress; October 20-24, 2023; Madrid, Spain. Abstract LBA47