Luveltamab tazevibulin (STRO-002), an anti-folate receptor alpha (FolRα) antibody drug conjugate (ADC), safety and efficacy in a broad distribution of FolRα expression in patients with recurrent epithelial ovarian cancer (OC): Update of STRO-002-GM1 phase 1 dose expansion cohort.

5508 Background: Luveltamab tazevibulin (luvelta) is a novel FolRα-targeting ADC with a stable cleavable linker and a 3-aminophenyl hemiasterlin warhead (DAR of 4) that induces cytotoxic and immunologic cell death. Using site-specific conjugation technology, luvelta is designed to target a broad range of FolRα expressing OC. STRO-002-GM1 is a global phase 1 study evaluating luvelta in patients with relapsed OC. We provide updated data from the initial ovarian expansion cohort. Methods: The study enrolled advanced OC pts who had progressive platinum resistant (PROC) after 1-3 prior lines or platinum sensitive disease after 2-3 prior lines of platinum chemotherapy. Pts were randomized 1:1 to received luveltamab at 4.3 or 5.2 mg/kg given IV every 3 weeks until disease progression. Prophylactic corticosteroid eyedrops were not required/administered. FolRα expression was not required for study entry but was analyzed retrospectively in archival tissue using the FOLR1 IHC assay (Ventana Medical Systems). The scoring paradigm assessed percentage of cells with any intensity expression (TPS). TPS >25% was selected for further analysis. Results: 44 pts were enrolled (23 pts at 4.3 mg/kg and 21 pts at 5.2 mg/kg). For pts with a TPS >25% (n=35), the median prior lines of therapy was 2.5 (range 1-3), 69% had prior bevacizumab treatment, and 83% prior PARP inhibitor treatment. Investigator assessed efficacy data for pts with a TPS >25% are presented in the table. The most common grade ≥ 3 treatment emergent adverse events (TEAEs) included neutropenia (70.5%), arthralgia (18.2%), and anemia (13.6%). G3/4 neutropenia had a higher incidence at 5.2 mg/kg than 4.3 mg/kg (76% vs 65%); most notable for G4 neutropenia (52% vs 22%). 1 pt at each dose level had febrile neutropenia. TEAEs led to dose delay in 80% of pts with a higher incidence at 5.2 mg/kg (95% vs. 65%). TEAEs led to dose reduction in 61% of pts with a higher incidence at 5.2 mg/kg (76% vs. 48%). 1 pt had a G5 sepsis with G4 neutropenia. Neutropenia, arthralgia and anemia were managed with standard medical treatment and dose reductions. Conclusions: These dose expansion data confirm activity of luvelta at starting doses ranging from 4.3-5.2 mg/kg in recurrent OC with FolRα expression as low as TPS>25% and supports further clinical study in this population. The global phase 2/3 REFRaME registration study will evaluate luvelta in PROC pts with TPS >25%. Clinical trial information: NCT03748186 . [Table: see text]