Farletuzumab ecteribulin, a folate receptor alpha (FRα) antibody-drug conjugate, in select advanced cancers: An open-label, multicenter, phase 1/2 dose-finding study

Wenham, Robert M., Ray-Coquard, Isabelle, Kristeleit, Rebecca, Matei, Daniela, Ghamande, Sharad and Jones, Robert H. ORCID: https://orcid.org/0000-0003-3576-9496 2026. Farletuzumab ecteribulin, a folate receptor alpha (FRα) antibody-drug conjugate, in select advanced cancers: An open-label, multicenter, phase 1/2 dose-finding study. Gynecologic Oncology 213 , pp. 109-119. 10.1016/j.ygyno.2026.08.023

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Abstract

Background In this phase 1/2 study, we assessed the safety/antitumor activity of farletuzumab ecteribulin (FZEC), a folate receptor alpha (FRα)-targeting antibody-drug conjugate, in patients with pretreated solid tumors. Methods Patients aged ≥18 years with measurable disease (per RECIST v1.1) were included. Patients with ovarian cancer (OC), endometrial cancer (EC), TNBC, and NSCLC were included in Dose-Escalation (0.9 mg/kg and 1.2 mg/kg IV Q3W). Patients with OC/EC were included for Dose-Confirmation (25 mg/m2 and 33 mg/m2 IV Q3W) and Dose-Optimization-part-A (8 mg/m2 D1/D8/D15, 12 mg/m2 D1/D8; 25 mg/m2 D1 + steroid IV Q3W). Results Eighty-nine patients were enrolled (median age: 67.0 years); most (88.7%) patients with OC and 50.0% patients with EC received ≥2 previous anticancer regimens. In Dose-Escalation (n = 25), interstitial lung disease (ILD)/pneumonitis occurred in 40% of patients. The dosing methodology was amended to body surface area-based dosing in subsequent study parts as an ILD/pneumonitis-mitigation strategy. In Dose-Confirmation (n = 24), 33.3% of patients experienced ILD/pneumonitis. In the 25 mg/m2 cohort, all ILD/pneumonitis events were grade-1/2. Evaluation of the 33 mg/m2 dose was discontinued due to observed ILD/pneumonitis. Dose equivalents of 25 mg/m2 were further evaluated in Dose-Optimization-part-A, with steroids/fractionated dosing (to mitigate ILD/pneumonitis). Patients receiving 8 mg/m2 D1/D8/D15 experienced no ILD/pneumonitis and achieved more responses versus other regimens, but the subgroup sizes were small. With steroids, incidence of ILD/pneumonitis was similar, but onset appeared delayed. Conclusions Fractionated doses of FZEC reduced the risk of ILD/pneumonitis and showed preliminary antitumor activity. Dose-Optimization-part-B will test additional FZEC fractionated doses (alone and in combination with lenvatinib) and concomitant steroid use.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Additional Information:	Full author list available at https://doi/org/10.1016/j.ygyno.2026.08.023
Publisher:	Elsevier BV
ISSN:	0090-8258
Date of First Compliant Deposit:	12 October 2026
Date of Acceptance:	30 August 2026
Last Modified:	12 Oct 2026 11:00
URI:	https://orca.cardiff.ac.uk/id/eprint/190141

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