Authors
Xiuning Le, Jie Wang, Yan Yu, Yanqiu Zhao, David Planchard, Bo Gao, Alexander Spira, Jingling Liu, Xingya Li, Shirish Gadgeel, Natasha Leighl, Junqiang Zhang, Hidetoshi Hayashi, Makoto Nishio, Julien Mazieres, Adrianus Johannes de Langen, Maurice Pérol, Kiyotaka Yoh, Martin D Forster, Yasushi Goto, Maria de Miguel Luken, Fernando Fabio Franco Perez, Quincy Chu, Sagun Parakh, Monique B Nilsson, Yong Jiang, Tianhua Hu, Cunlin Wang, Nichole Baio, Luna Musib, Zineb Mounir, Marcin Kowanetz, Shirley Wang, Steven Yea, Jerry Hsu, Stuart Lutzker, John V Heymach, Oscar Juan-Vidal, Jonathan W Riess
Published in
Cancer cell. Oct 16, 2026. Epub Oct 16, 2026.
Abstract
P-loop and αC-helix compressing (PACC) mutations comprise a structurally distinct subgroup of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) with limited treatment options. Firmonertinib is a once-daily oral, brain-penetrant, mutant-selective EGFR tyrosine kinase inhibitor with a unique trifluoroethoxy side chain. Firmonertinib had high anti-proliferative efficacy in EGFR PACC-mutant cells and xenografts. In the phase 1b FURTHER study (NCT05364073), patients with metastatic EGFR PACC-mutant NSCLC randomized to receive first-line firmonertinib 160 mg (n = 25) or 240 mg (n = 22) had confirmed objective response rates (ORRs) of 43% and 68%, median duration of response not reached and 14.6 months, and median progression-free survival of 11.1 and 16.0 months, respectively; treatment-related adverse events led to dose reductions (19% and 24%) and discontinuation (3% and 0%). Intracranial ORR among patients with brain metastases at baseline was 47% (8/17). Results support further study of first-line firmonertinib in patients with EGFR PACC-mutant NSCLC.
PMID:
42887497
Bibliographic data and abstract were imported from PubMed on 17 Oct 2026.
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