Tipifarnib Shows Responses in HRAS-Mutant Head and Neck Cancers

A subset of metastatic head and neck squamous cell carcinoma (HNSCC) with mutations of the HRAS gene showed responses to the compound tipifarnib, an inhibitor of the enzyme farnesyltransferase, according to data presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics held in Boston from October 26, 2019 to October 30, 2019. The phase II results apply to roughly 5 to 8% of patients with advanced HNSCC who show the HRAS mutation. 

“Tipifarnib may represent a promising new therapy for HRAS-mutant HNSCC patients,” said Alan L. Ho, MD, PhD, a Memorial Sloan Kettering Cancer Center medical oncologist, and one of the lead investigators of the trial. “The success of the trial also speaks to the promise of utilizing genomic sequencing of disease to identify highly effective therapies that are personalized to the specific biology of each individual patient’s tumor.”

The latest look at the drug’s use in head and neck cancers was focused on 23 patients with HNSCC and 10 with other squamous cell carcinomas with HRAS mutations. All subjects had relapsed/refractory disease with a median of 2 prior treatments and had to have progressed on previous treatment (including platinum therapy, immunotherapy, or cetuximab). 

“The patients received a 600 mg dose of tipifarnib twice daily (1200 mg total) on days 1 through 7 and days 15 through 21 of the 28-day cycle, according to the data.”

Researchers said they met the durable response rate objective before the study was finished. The primary object was thus “amended to enrich for patients most likely to respond by recruiting only those patients with HNSCC tumors that had HRAS missense mutations at a high variant allele frequency (VAF; 35% or higher); those with a VAF of 20 % or higher were also enrolled if their baseline serum albumin was at least 3.5 g/dL.” The testing has prompted a start of first-line HRAS-mutation HNSCC tests, according to the abstract. 

“This is another example of how understanding the genomics and biology of a disease can be leveraged to develop new and effective cancer therapies,” concluded Ho. 

Tipifarnib has previously been tested in plexiform neurofibromas, as well as for AML, according to the literature available online. The latest study is sponsored by Kura Oncology.

References:

Ho A, Brana I, Haddad R, et al. Preliminary results from a phase 2 trial of tipifarnib in squamous cell carcinomas (SCCs) with HRAS mutations. Abstract presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics. Boston, October 26-30, 2019.

Kura Oncology. Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations.
Available from: https://clinicaltrials.gov/ct2/show/results/NCT02383927 .
ClinicalTrials.gov Identifier: NCT02383927. Accessed October 39, 2019.