FURTHER: A global study to evaluate furmonertinib in patients with EGFR mutant NSCLC including uncommon EGFR mutations (FURMO-002).

Xiuning Le The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Xiuning Le, Alexander I. Spira, Shirish M. Gadgeel, Jonathan W. Riess, Yan Yu, Yanqiu Zhao, Ying Cheng, Oscar Juan-Vidal, Bo Gao, Kiyotaka Yoh, Martin Forster, Satoru Kitazono, Hidetoshi Hayashi, David Planchard, Yong Jiang, Nichole Baio, Marcin Kowanetz, William Leung, Jerry Y. Hsu, Jie Wang

Authors Xiuning Le The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Xiuning Le, Alexander I. Spira, Shirish M. Gadgeel, Jonathan W. Riess, Yan Yu, Yanqiu Zhao, Ying Cheng, Oscar Juan-Vidal, Bo Gao, Kiyotaka Yoh, Martin Forster, Satoru Kitazono, Hidetoshi Hayashi, David Planchard, Yong Jiang, Nichole Baio, Marcin Kowanetz, William Leung, Jerry Y. Hsu, Jie Wang Organizations The University of Texas MD Anderson Cancer Center, Houston, TX, NEXT Oncology Virginia, Fairfax, VA, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, UC Davis Comprehensive Cancer Center, Sacramento, CA, Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China, Henan Cancer Hospital, Zhengzhou, China, Jilin Cancer Hospital, Changchun, China, Hospital Universitario y Politécnico La Fe, Valencia, Spain, Blacktown Cancer and Haematology Centre, Blacktown Hospital, Blacktown, NSW, Australia, National Cancer Center Hospital East, Kashiwa, Japan, University College London Cancer Institute, University College London Hospital NHS Trust, London, United Kingdom, Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan, Kindai University Hospital, Osaka, Japan, Gustave Roussy, Department of Medical Oncology, Thoracic Group, Villejuif, France, Allist Pharmaceuticals, Shanghai, China, ArriVent Biopharma, Newtown, PA, ArriVent Biopharma, Burlingame, CA, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China Abstract Disclosures Research Funding No funding sources reported Background: Furmonertinib (AST2818) is an oral, highly brain-penetrant, and broadly active mutation-selective epidermal growth factor receptor ( EGFR) inhibitor engineered for broad activity and selectivity across EGFR mutations (mts) (1). Furmonertinib is approved in China for first-line advanced NSCLC with EGFR Ex19del or L858R mts based on the progression-free survival benefit observed in the Phase 3 study versus gefitinib (FURLONG). Furmonertinib has also demonstrated promising interim efficacy and safety in patients (pts) with NSCLC harboring EGFR exon 20 insertion (ex20ins) mts with a confirmed overall response rate (ORR) of 78.6% (n=28) by blinded independent central review (BICR) and a preliminary median duration of response (DoR) of 15.2 months in the front-line setting (FAVOUR study; see Han et al., WCLC 2023). Furmonertinib recently obtained FDA Breakthrough Therapy Designation for the treatment of pts with advanced NSCLC with EGFR ex20ins mts. P-loop and αC-helix Compressing (PACC) mts represent another subset of uncommon EGFR mts (2) that are similar to ex20ins mts in narrowing the drug-binding pocket; including G719X, S768I, E709X, L747X, V774M. Preclinical data indicating that furmonertinib is potent in models harboring EGFR PACC mts Developing efficacious, well-tolerated, and CNS-penetrant medicines for NSCLC pts with EGFR ex20ins mts and PACC mts remains an unmet need. Methods: FURTHER (FURMO-002) is the first global trial evaluating furmonertinib in NSCLC pts with EGFR and HER2 mts in North America, Europe, and the Asia-Pacific. FURTHER is a phase 1b, open-label, multicenter study in which pts will be treated orally with furmonertinib daily. For Stage 1 dose-escalation, the primary endpoint is incidence and severity of adverse events, including dose limiting toxicities and has been completed. For Stage 2 dose expansion, approximately 120 pts will be enrolled across 4 expansion cohorts. Stage 2 Cohorts 1-3 dose expansion cohorts will enroll pts with previously treated, locally advanced or metastatic NSCLC pts with either EGFR ex20ins mts, HER2 ex20ins mts, or EGFR activating mts, respectively. Cohorts 1-3 allow enrollment of pts with prior EGFR or HER2-directed therapy. Stage 2 Cohort 4 will enroll EGFR TKI-naïve NSCLC pts with EGFR PACC mts. Key inclusion criteria include documented EGFR or HER2 mts by local testing and measurable disease per RECIST v1.1. Stage 2 primary endpoint is ORR using RECIST v1.1. Key secondary endpoints include progression-free survival and overall survival. Stage 2 enrollment is ongoing. 1. Musib et al., NACLC 2022. 2. Robichaux et al., 2021. Clinical trial information: NCT05364073.

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