Abstract 1561: Antitumor effect of farletuzumab ecteribulin in molecular subtypes of endometrial cancer patient-derived xenograft models

Abstract Background: Endometrial cancer (EC) represents a significant health burden globally, particularly in postmenopausal women. Current treatment options for advanced-stage EC remain limited, emphasizing the need for novel therapeutic strategies. This study aimed to investigate farletuzumab ecteribulin (FZEC), an antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα), as a potential new therapeutic agent for EC using tumor models. Methods:We utilized a panel of 24 patient-derived xenograft (PDX) models, representing various histological and molecular subtypes of EC with different levels of FRα expression, to evaluate the antitumor effect of FZEC. FZEC was administered intravenously at doses of 5 mg/kg and 12.5 mg/kg. Intratumoral accumulation of eribulin, the payload of FZEC, was visualized using phosphor-integrated dot imaging. Results:FZEC demonstrated dose-dependent antitumor effects across the EC-PDX panel. At 5 mg/kg, the FZEC efficacy was associated with FRα expression, with 100% of FRα 3+ models exhibiting tumor shrinkage compared to 27.2% of FRα-negative models. FZEC also demonstrated broad activity across both histological and molecular subtypes of EC. Intratumoral eribulin accumulation was highly correlated with antitumor effects, even in models with low FRα expression. Follow-up studies confirmed FRα-dependent antitumor effects, while also indicating potential FRα-independent mechanisms of action. Conclusion:FZEC demonstrated robust antitumor effect against the FRα high EC-PDX models. Importantly, significant antitumor effects were observed, even in FRα-low or negative models. Intratumoral eribulin accumulation exhibited a stronger correlation with efficacy than with FRα expression alone. These results support further clinical development of FZEC for EC treatment and highlight the complexity of ADC mechanisms of action. Citation Format: Shigehiro Yagishita, Sho Sato, Daisuke Shintani, Tadaaki Nishikawa, Aiko Ogasawara, Masanori Yasuda, Hironori Ishii, Keiji Furuuchi, Toshimitsu Uenaka, Hiroshi Yoshida, Kosei Hasegawa, Akinobu Hamada. Antitumor effect of farletuzumab ecteribulin in molecular subtypes of endometrial cancer patient-derived xenograft models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1561.