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Molecular Profile HRAS mutant
Therapy Tipifarnib
Indication/Tumor Type head and neck squamous cell carcinoma
Response Type predicted - sensitive

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
HRAS mutant head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Phase II Actionable In a Phase II trial (AIM-HN), Zarnestra (tipifarnib) demonstrated safety and preliminary activity in patients with recurrent or metastatic head and neck squamous cell carcinoma harboring mutations in HRAS, resulting in an objective response rate of 20% (10/50, 1 complete and 9 partial responses), disease control rate of 48% (24/50), with stable disease in 14 patients, median progression-free survival of 2.6 mo, and median overall survival of 7 mo (Ann Oncol (2023) 34 (suppl_2): S1286-S1287; NCT03719690). detail...
HRAS mutant head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Phase II Actionable In a Phase II trial (KO-TIP-001), Zarnestra (tipifarnib) treatment resulted in an objective response rate of 55% (11/20) in patients with head and neck squamous cell carcinoma harboring HRAS missense mutations at a variant allele frequency over 20%, with nine patients achieved stable disease and a median progression-free survival of 5.6 months (PMID: 33750196; NCT02383927). 33750196
HRAS mutant head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cell lines harboring an HRAS mutation were sensitive to treatment with Zarnestra (tipifarnib), demonstrating reduced cell growth and decreased phosphorylation of Erk and Mek, and inhibition of spheroid viability in culture (PMID: 32727882). 32727882
PubMed Id Reference Title Details
(32727882) Tipifarnib as a Precision Therapy for HRAS-Mutant Head and Neck Squamous Cell Carcinomas. Full reference...
(33750196) Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations. Full reference...
LBA47 A phase II study evaluating tipifarnib in mHRAS, recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (AIM-HN study) Full reference...