The AIM-HN and SEQ-HN study
Research type
Research Study
Full title
The AIM-HN and SEQ-HN Study: A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC) with HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN).
IRAS ID
252909
Contact name
Kevin Harrington
Contact email
Sponsor organisation
Kura Oncology, Inc.
Eudract number
2018-001437-40
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
127,209, IND
Duration of Study in the UK
3 years, 8 months, 20 days
Research summary
Head and neck squamous cell carcinoma (HNSCC) accounts for more than 550,000 cases annually, worldwide, with incidence rates of certain subtypes (oropharyngeal) on the rise. Kura Oncology is conducting this research study to investigate if study medication, Tipifarnib, is safe and effective to use in participants with HNSCC, with HRAS gene mutations. The HRAS gene provides instructions for regulating cell division and when mutated has the potential to cause cells to become cancerous.
The study is made up of two parts and participants will be enrolled dependent on the results of a pre-screening assessment for HRAS mutations. It has been reported that HNSCC patients with HRAS mutations do not respond as well to some treatment options. If the pre-screening results indicate there is a HRAS mutation, participants may be eligible to participate in the treatment portion of the study called AIM-HN. If there is no HRAS mutation present, participants may be able to participate SEQ-HN (non-treatment portion of the study). Approximately 59 and 225 participants worldwide are expected to enrol in AIM-HN and SEQ-HN, respectively.
Participants enrolled in AIM-HN will take study medication orally, twice a day, in 28-day cycles. Duration of participation in the study will depend on participant’s study medicine tolerance, tumour response, and overall condition. Participants in AIM-HN will undergo a series of procedures, including providing blood samples, physical examinations/general assessments and tumour assessment scans during the study.
The purpose of SEQ-HN observational portion of the study is to assess how participants without an HRAS mutation respond to treatment for their HNSCC compared to participants who have an HRAS mutation to improve understanding. In this part of the study, patients will be asked to provide a single blood sample and will be contacted regularly by the study team for follow up. No medication will be administered.
Lay summary of study results: This study had 1 sub-study to assess the antitumor activity of the study drug tipifarnib in subjects with head and neck squamous cell carcinomas (HNSCC) with HRAS mutations (called AIM-HN), and who had received at least one prior platinum-containing regimen (recurrent/metastatic disease), and 1 sub-study to assess the impact of HRAS mutational status on response to first line systemic therapies for HNSCC (called SEQ-HN).
The primary study objective for the AIM-HN study was to determine the objective response rate (ORR) of tipifarnib in subjects with HNSCC with HRAS mutations with a variant allele frequency (VAF) ≥20% (called high VAF population), as assessed by an Independent Review Facility (IRF).
Subjects enrolled in AIM-HN received tipifarnib at a dose of 600 mg, orally, twice a day, on Days 1-7 and 15-21 of 28-day cycles. Subjects enrolled in SEQ-HN did not receive any tipifarnib treatment. In the AIM-HN study, a total of 59 subjects were enrolled and all 59 subjects received at least 1 dose of tipifarnib. In the SEQ-HN study, a total of 237 subjects were enrolled.
All 59 subjects in the AIM-HN and all 237 subjects in the SEQ-HN discontinued the study. The main reason for study discontinuation was death, with 40 deaths (67.8%) in AIM-HN and 149 deaths (62.9%) in SEQ-HN.
In the AIM-HN study, all 59 subjects discontinued the study treatment. The main reason was progressive disease. In the AIM-HN study, for subjects with high VAF, the ORR based on the IRF was 20%, with 1 subject achieving complete response and 9 subjects achieving partial response.
Overall Conclusions: Tipifarnib monotherapy was shown to have an acceptable safety and tolerability profile at 600 mg twice daily in alternating weeks in subjects with HRAS mutant recurrent/metastatic HNSCC. Tipifarnib demonstrated antitumor activity and clinical benefit for HRAS mutant, recurrent/metastatic HNSCC subjects with high VAF.
REC name
London - Riverside Research Ethics Committee
REC reference
19/LO/0271
Date of REC Opinion
25 Apr 2019
REC opinion
Further Information Favourable Opinion