Phase 2
Completed N=296
Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy
HRAS Gene Mutation · HNSCC
Source: ClinicalTrials.gov NCT03719690 ↗
Enrolled (actual)
296
Serious AEs
47.5%
Results posted
Jun 2024
Primary outcomePrimary: Objective Response Rate (ORR) in High Variable Allele Frequency (VAF) Population, as Assessed by Independent Review Facility (IRF) — 20.0 percentage of participants
Summary
An international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN). The first cohort will assess the objective response rate (ORR) of tipifarnib in subjects with HNSCC with HRAS mutations. The second study cohort, SEQ-HN, is an observational sub-study including HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Objective Response Rate (ORR) in High Variable Allele Frequency (VAF) Population, as Assessed by Independent Review Facility (IRF) |
20.0 | — |
| SECONDARY ORR in All VAF Population, as Assessed by IRF |
18.6 | — |
| SECONDARY Duration of Response (DoR) in High VAF Population, as Assessed by IRF |
6.51 | — |
| SECONDARY DoR in All VAF Population, as Assessed by IRF |
6.51 | — |
| SECONDARY Progression Free Survival (PFS) in High VAF Population, as Assessed by IRF |
2.60 | — |
| SECONDARY PFS in All VAF Population, as Assessed by IRF |
2.23 | — |
| SECONDARY PFS Rate in High VAF Population, as Assessed by IRF |
29; 20 | — |
| SECONDARY PFS Rate in All VAF Population, as Assessed by IRF |
26; 18 | — |
| SECONDARY Overall Survival (OS) in High VAF Population |
6.97 | — |
| SECONDARY OS in All VAF Population |
6.21 | — |
| SECONDARY OS Rate at 12 Months in High VAF Population |
31 | — |
| SECONDARY OS Rate at 12 Months in All VAF Population |
30 | — |
| SECONDARY Time to Response (TTR) in High VAF Population, as Assessed by IRF |
1.9 | — |
| SECONDARY TTR in All VAF Population, as Assessed by IRF |
1.9 | — |
| SECONDARY Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs) |
58; 43 | — |
| SECONDARY Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module 35 (EORTC QLQ-H&N35) Subscales |
0.0; 8.3; 0.0; 0.0 | — |
| SECONDARY Change From Baseline in the EuroQol-Visual Analog Scale (EQ-VAS) Score |
3.5 | — |
Eligibility Criteria
Inclusion Criteria
AIM-HN
- At least 18 years of age.
- Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
- Documented treatment failure from most recent prior therapy (e.g. tumor progression, clinical deterioration, or recurrence), and from at least one prior platinum-containing regimen, in any treatment setting.
- Known tumor missense HRAS mutation.
- Measurable disease by RECIST v1.1.
- ECOG performance status of 0-1.
- Acceptable liver, renal and hematological function
- Other protocol defined inclusion criteria may apply.
Exclusion Criteria
- Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).
- Received treatment for unstable angina within prior year, myocardial infarction within the prior year, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
- Non-tolerable Grade 2 or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
- Active, uncontrolled bacterial, viral or fungal infections requiring systemic therapy. Known history of infection with human immunodeficiency virus or an active infection with hepatitis B or hepatitis C.
- Received treatment for non-cancer related liver disease within prior year.
- Other protocol defined exclusion criteria may apply
Inclusion Criteria: SEQ-HN
- At least 18 years of age.
- Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology.
- Will or has received at least one systemic anti-cancer therapy for recurrent or metastatic HNSCC.
- HRAS wildtype (i.e., have no identified tumor missense HRAS mutation).
- Other protocol defined inclusion criteria may apply
Exclusion Criteria: SEQ-HN
- Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).
- Other protocol defined exclusion criteria may apply
Data sourced from ClinicalTrials.gov (NCT03719690). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.