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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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