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Association details:
| Biomarker: | HRAS mutation |
|---|---|
| Cancer: | Squamous Cell Carcinoma of Head and Neck |
| Drug: | Zarnestra (tipifarnib) (CXCL12 inhibitor, Farnesyl transferase inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Kura Oncology Receives FDA Breakthrough Therapy Designation for Tipifarnib in Head and Neck Squamous Cell Carcinoma
Published date:
02/24/2021
Excerpt:
Kura Oncology...a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, today announced that its investigational drug, tipifarnib, has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with recurrent or metastatic HRAS mutant head and neck squamous cell carcinoma (HNSCC) with variant allele frequency ≥ 20% after disease progression on platinum-based chemotherapy.
Source:
Title:
Kura Oncology Receives Fast Track Designation for Tipifarnib in HRAS Mutant HNSCC and Provides Enrollment Guidance for AIM-HN Trial
Published date:
12/16/2019
Excerpt:
Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for the treatment of cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to the Company’s lead drug candidate, tipifarnib, for the treatment of patients with HRAS mutant head and neck squamous cell carcinomas (HNSCC) after progression on platinum therapy.
Source:
Title:
Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations
Excerpt:
...- tumor that carries a missense HRAS mutation ith a variant allele frequency (VAF) > 20%....
Trial ID:
Source:
Title:
Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy
Excerpt:
...Known tumor missense HRAS mutation....
Trial ID:
Less C2 evidence
Source:
Title:
HRAS Mutations Define a Distinct Subgroup in Head and Neck Squamous Cell Carcinoma
Published date:
01/07/2023
Excerpt:
Two hundred forty-nine patients with HRAS-mutant HNSCC were identified from the four data sets….Use of tipifarnib in this data set demonstrated improved OS (25.5 months; 95% CI, 18.0 to 48.0).
DOI:
10.1200/PO.22.00211
Source:
Title:
Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations
Published date:
05/19/2021
Excerpt:
Tipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with HRAS mutations....Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7).
DOI:
10.1200/JCO.20.02903
Trial ID:
Source:
Title:
Preliminary activity of tipifarnib in tumors of the head and neck, salivary gland and urothelial tract with HRAS mutations.
Published date:
05/13/2020
Excerpt:
...21 HNSCC pts meeting the high HRASm VAF criteria had been treated with tipifarnib of whom 18 were efficacy evaluable at data cut off. Pts had received a median of 2 prior systemic regimens. Ten objective responses were observed in 18 evaluable pts for an ORR of 56%.
DOI:
10.1200/JCO.2020.38.15_suppl.6504
Source:
Title:
Preliminary results from a phase II trial of tipifarnib in squamous cell carcinomas (SCCs) with HRAS mutations
Published date:
10/01/2018
Excerpt:
HNSCC pts are currently evaluable for efficacy; 5 (71%) achieved a confirmed partial response with a median duration of response of 14.1 months (95% CI: 1.4-17.3 mo), exceeding the pre-specified null hypothesis….Encouraging activity of tipifarnib was observed in pts with HRAS mutant HNSCCs.
DOI:
https://doi.org/10.1093/annonc/mdy287.002
Trial ID:
Source:
Title:
Antitumor activity of tipifarnib and PI3K pathway inhibitors in HRAS-associated HNSCC.
Published date:
05/28/2020
Excerpt:
Regressions with the FTI-PI3K-a inhibitor doublet were observed both in tumors that were WT or harbored hotspot mutations or amplification of the PIK3CA gene and in HRAS mutants that carried or lacked PIK3CA mutations.
DOI:
10.1200/JCO.2020.38.15_suppl.e15658
Source:
Title:
Tipifarnib as a Precision Therapy for HRAS-Mutant Head and Neck Squamous Cell Carcinomas
Excerpt:
Tipifarnib treatment displaced both mutant and wild type HRAS from membranes but only inhibited proliferation, survival and spheroid formation of HRAS mutant cells….In vivo, tipifarnib treatment induced tumor stasis or regression in all six HRAS mutant xenografts tested...
DOI:
10.1158/1535-7163.MCT-19-0958
