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

@article{wenham2026farletuzumab,
  title = {{Farletuzumab ecteribulin, a folate receptor alpha (FRα) antibody-drug conjugate, in select advanced cancers: An open-label, multicenter, phase 1/2 dose-finding study}},
  author = {Robert Wenham and Isabelle Ray-Coquard and Rebecca Kristeleit and Daniela Matei and Sharad Ghamande and Ana Oaknin and Jonathan Berek and J Alejandro Perez-Fidalgo and Pau Guillén Sentís and Eva Guerra Alia and June Hou and Phillipe Follana and Lauriane Eberst and Andrew Clamp and Jean-Sebastien Frenel and Patricia Roxburgh and Robert Jones and Patricia Pautier and Amanda Jackson and Deborah Armstrong and Tingting Song and Maiko Nomoto and Natalyn Hawk and Rachael Scott and Vicky Makker and J. Alejandro Perez-Fidalgo},
  journal = {Gynecologic Oncology},
  year = {2026},
  month = oct,
  doi = {10.1016/j.ygyno.2026.08.023},
  url = {https://hal.science/hal-05801041v1},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Farletuzumab ecteribulin, a folate receptor alpha (FRα) antibody-drug conjugate, in select advanced cancers: An open-label, multicenter, phase 1/2 dose-finding study
AU  - Robert Wenham
AU  - Isabelle Ray-Coquard
AU  - Rebecca Kristeleit
AU  - Daniela Matei
AU  - Sharad Ghamande
AU  - Ana Oaknin
AU  - Jonathan Berek
AU  - J Alejandro Perez-Fidalgo
AU  - Pau Guillén Sentís
AU  - Eva Guerra Alia
AU  - June Hou
AU  - Phillipe Follana
AU  - Lauriane Eberst
AU  - Andrew Clamp
AU  - Jean-Sebastien Frenel
AU  - Patricia Roxburgh
AU  - Robert Jones
AU  - Patricia Pautier
AU  - Amanda Jackson
AU  - Deborah Armstrong
AU  - Tingting Song
AU  - Maiko Nomoto
AU  - Natalyn Hawk
AU  - Rachael Scott
AU  - Vicky Makker
AU  - J. Alejandro Perez-Fidalgo
PY  - 2026
DA  - 2026/10/15
JO  - Gynecologic Oncology
DO  - 10.1016/j.ygyno.2026.08.023
UR  - https://hal.science/hal-05801041v1
AB  - 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/m 2 and 33 mg/m 2 IV Q3W) and Dose-Optimization-part-A (8 mg/m 2 D1/D8/D15, 12 mg/m 2 D1/D8; 25 mg/m 2 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/m 2 cohort, all ILD/pneumonitis events were grade-1/2. Evaluation of the 33 mg/m 2 dose was discontinued due to observed ILD/pneumonitis. Dose equivalents of 25 mg/m 2 were further evaluated in Dose-Optimization-part-A, with steroids/fractionated dosing (to mitigate ILD/pneumonitis). Patients receiving 8 mg/m 2 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.
SN  - 0090-8258
SN  - 1095-6859
ER  -