Reframe-O1/engot-Ov79/gog-3086: a Phase 2/3 Open-Label Study Evaluating the Efficacy and Safety of Luveltamab Tazevibulin Versus Investigator's Choice Chemotherapy

Abstract

Introduction Folate receptor alpha (FolRa) is a validated target in the treatment of platinum resistant ovarian cancer (PROC) expressing high-FolRa. There remains a high unmet need to treat PROC with low to moderate FolRa expression. Luveltamab tazevibulin (luvelta), a novel FolRa-targeting ADC with a hemiasterlin warhead (DAR4), is designed using site-specific conjugation technology to target a broad range of FolRa-expressing cancers. Luvelta demonstrated preliminary efficacy data (ORR of 37.5%; mDOR of 5.5 months; mPFS of 6.1 months) in 32 patients with advanced/relapsed EOC with FolRa expression of >25% (any intensity) in a Ph1 study (NCT03748186). ORR was higher at 5.2 mg/kg (43.8% versus 31.3%, n=32) compared to 4.3 mg/kg. Luvelta showed a manageable safety profile, with the most common grade 3+ adverse events of neutropenia, arthralgia, and anemia. This data forms the basis for a pivotal study of luvelta in patients with PROC with broad FolRa expression levels. Methods REFRaME-O1/ENGOT-Ov79/GOG-3086 is a 2-part Phase 2/3 study of luvelta in subjects with relapsed PROC expressing FolRa. Part 1 is the dose-optimization stage, with ~50 subjects randomized 1:1 at 4.3 mg/kg Q3W or 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 versus investigator's choice chemotherapy, with a 2:1 randomization schedule. Key inclusion criteria: progressive PROC, up to 3 prior regimens, TPS of >=25% for FolRa expression, and measurable disease. Key exclusion criteria: primary platinum refractory disease and prior treatment with a FolRa ADC or ADC-containing tubulin inhibitor. Current Trial Status Currently enrolling.