Reference Detail

Ref Type

Abstract

PMID

Authors

A.L. Ho D.R. Adkins G.J. Hanna J. Bruce M-J. Ahn L. Iglesias Docampo H. Kang D.J. Wong A. Psyrri M. Gillison I. Braña Y.C. Liu C-Y. Hsieh M.H. Hong Z. Zhang B. Balsara A. Saunders A. Gasco Hernandez S. Dale R. Haddad

Title

LBA47 A phase II study evaluating tipifarnib in mHRAS, recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (AIM-HN study)

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	34	Supplement 2	October 2023	S1286-S1287	Ann Oncol

URL

https://www.annalsofoncology.org/article/S0923-7534(23)04185-6/fulltext

Abstract Text

Background Despite recent advances, prognosis for R/M HNSCC patients (pts) remains poor. HRAS mutations are seen in 4-8% of HNSCCs. HRAS is uniquely farnesylation dependent, making mHRAS tumors susceptible to farnesyl transferase inhibitors. Tipifarnib has activity in pts with HNSCC harboring high variant allele frequency (VAF, ≥20%) mHRAS (Ho et al. JCO 2021). We present data in 50 high VAF pts in AIM-HN. Methods Pts received tipifarnib 600 mg BID on days 1-7 and 15-21 of a 28-day cycle. The primary endpoint was objective response rate (ORR) in the high VAF pts by independent review facility (IRF). Histologically confirmed mHRAS HNSCC pts with ≥1 prior platinum-containing regimen were eligible. ORR was assessed in the modified intent to treat (mITT) set (≥1 tipifarnib dose). Results Of 59 pts treated with tipifarnib, 50 (85%) had high VAF (median VAF: 34% [range 4-89%]). Twenty-six (44%) received immunotherapy in 1st line (1L). By Investigator assessment, ORR was 30% with 1 pt achieving a CR. By IRF, ORR was 20% with 1 CR (Table). Two responders were on treatment at study close (9 and 29 mos). Median progression-free survival by IRF: 2.6 mos (95% CI: 1.9-4.4); median overall survival: 7.0 mos (95% CI: 4.9-11.5). Grade 3+ treatment-related adverse events (TRAEs) were observed in 33 pts (56%): neutropenia (24%), anemia (20%), leukopenia (14%) and febrile neutropenia (7%). However, only 7% discontinued treatment due to TRAEs. Conclusions Tipifarnib was safe and tolerable with anti-tumor activity observed in mHRAS R/M HNSCC pts post-IO and as later-line therapy. Tipifarnib is the first targeted therapy for this rare HNSCC subset. Ongoing combination studies are targeting adaptive resistance pathways (PI3K/mTOR/Akt) to further improve outcomes.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

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...