REFRaME-O1/ENGOT-OV79/GOG-3086: A phase II/III, open-label study evaluating the efficacy and safety of luveltamab tazevibulin versus investigator's choice of chemotherapy in women with relapsed platinum-resistant epithelial ovarian cancer expressing folate receptor alpha

Abstract

Objectives: The primary objective of the study is to evaluate the efficacy (primary endpoint progression-free survival) of luveltamab tazevibulin in subjects with relapsed platinum-resistant epithelial ovarian cancer expressing FOLRalpha. The secondary objectives are to evaluate additional efficacy measures (overall survival as key secondary endpoint) and safety and tolerability of luveltamab tazevibulin in subjects with relapsed platinum-resistant epithelial ovarian cancer expressing FOLRalpha. Exploratory: To assess the incidence of study drug immunogenicity, pharmacodynamic effects and pharmacokinetics Methods: REFRaME-O1 is a multicenter, international, open-label, 2-part seamless phase II/III study of luveltamab tazevibulin in subjects with relapsed platinum-resistant ovarian cancer (PROC) expressing FolRalpha. Part 1 consists of a dose-optimization stage and will randomize ~50 subjects 1:1 to the treatment of luveltamab at 4.3 mg/kg Q3W or luveltamab 5.2 mg/kg Q3W + prophylactic pegfilgrastim for 2 cycles followed by 4.3 mg/kg Q3W. Part 2 will commence with the selected optimized dose and randomization to luveltamab tazevibulin or the investigator's choice of chemotherapy. Key inclusion criteria are progressive PROC, up to 3 prior regimens, tumor proportion score by immunohistochemistry of >=25 % for FolRalpha expression, and measurable radiologic disease. Key exclusion criteria are primary platinum-refractory disease and prior treatment with a FolRalpha targeting antibody-drug conjugate (ADC) or ADC containing a tubulin inhibitor.