Gynecologic oncology · 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.
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Wenham Robert M, Ray-Coquard Isabelle, Kristeleit Rebecca, Matei Daniela, Ghamande Sharad, Oaknin Ana, Berek Jonathan S, Perez-Fidalgo J Alejandro, Sentís Pau Guillén, Guerra Alia Eva M, Hou June, Follana Phillipe, Eberst Lauriane, Clamp Andrew, Frenel Jean-Sebastien, Roxburgh Patricia, Jones Robert H, Pautier Patricia, Jackson Amanda L, Armstrong Deborah K, Song Tingting, Nomoto Maiko, Hawk Natalyn, Scott Rachael, Makker Vicky
Аннотация
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. Clinical Trial Registration #: NCT04300556.
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. Clinical Trial Registration #: NCT04300556.