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

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.