Abstract PR08: Preliminary results from a phase 2 trial of tipifarnib in squamous cell carcinomas (SCCs) with HRAS mutations

Alan Ho, Irene Brana, Robert Haddad, Jessica Bauman, Keith Bible, Laurence Faugeras, Sjoukje Oosting, Deborah J Wong, Myung-Ju Ahn, Valentina Boni, Caroline Even, Jerome Fayette, Maria Flor, Kevin Harrington, Sung-Bae Kim, Lisa Licitra, Ioanna Nixon, Nabil F Saba, Cyrus Sayehli, Pol SpecenierFrancis Worden, Binaifer Balsara, Jeanne Britt, Vishnu Mishra, Catherine Scholz, Antonio Gualberto

Research output: Contribution to journalMeeting abstractpeer-review


Background: This Phase 2 study (NCT02383927) is a multi-institutional, open-label trial to determine the efficacy and safety of tipifarnib in patients (pts) with locally advanced/unresectable and/or metastatic solid tumors that carry HRAS missense mutations. HRAS is a proto-oncogene that is overexpressed and mutated in head and neck squamous cell carcinomas (HNSCC) and other SCCs. Tipifarnib is a potent and highly selective inhibitor of farnesyltransferase, a critical enzyme for HRAS activity. Methods: Pts received tipifarnib at a starting dose of 600 – 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles. Disease assessments were conducted according to RECIST v1.1 criteria. Null hypothesis and objective response of interest were respectively 10% and 30%. Prior to its completion, this study met its primary objective and, based on preliminary efficacy results (Ho, et. al, ESMO 2018), was amended to continue enrolling only pts with HNSCC (Cohort 2) and other SCC tumors (Cohort 3) carrying HRAS missense mutations at a high variant allele frequency (VAF >35% or ≥20% if baseline serum albumin is >3.5 g/dL). Results: As of May 1, 2019, 23 pts with HNSCC and 10 pts with tumors with other SCC histologies have been treated with tipifarnib. Pts had relapsed/refractory disease with a median of 2 prior regimens. Of note, no objective partial responses were observed on their last therapy prior to study entry, including platinum, immunotherapy and cetuximab +/- chemotherapy. In 15 HNSCC pts meeting the HRAS mutation high VAF inclusion criteria, a 53% overall response rate (ORR) was observed, with 8 confirmed partial responses (PR) and 5 disease stabilizations (SD). Two pts await first on-study tumor response assessment. Overall median progression free survival (PFS) was 5.4 mos (95% CI 4.5 to 19.5 mos, N=15); 19 mos (95% CI 5.3 to 19.5 mos) for pts experiencing a PR and 4.5 mos (95% CI 1.6 to 5.4 mos) for those experiencing SD. Median PFS on last prior therapy was 3.2 mos. All pts had at least 1 treatment-emergent adverse event (TEAE). The most frequently observed drug-related Grade >3 TEAEs occurring in ≥10% pts were blood and lymphatic system disorders, gastrointestinal disorders and renal disorders. Conclusions: Encouraging activity of tipifarnib was observed in HRAS mutant HNSCC. Based on these data, a pivotal study (AIM-HN and SEQ-HN Study, NCT03719690) evaluating the efficacy of this agent in HRAS mutant HNSCC (AIM-HN) and the impact of HRAS mutations on first line therapy of HNSCC (SEQ-HN) has been initiated.
Original languageEnglish
JournalMolecular Cancer Therapeutics
Issue number12 Supplement
Publication statusPublished - 1 Dec 2019
EventAACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics - Boston, MA, United States
Duration: 26 Oct 201930 Oct 2019


  • tipifarnib
  • squamous cell carcinomas
  • HRAS mutations


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