Phase 1 study of BAT8006, a folate receptor α antibody drug conjugate with strong bystander effect, in subjects with advanced solid tumors.

5550 Background: BAT8006 is an antibody-drug conjugate targeting to folate receptor α (FRα). In this phase 1 study, the authors investigated BAT8006 in subjects with solid tumors. Methods: Subjects with advance solid tumor received BAT8006 on day 1 of a 21-day cycle until subject intolerance or disease progression. The study objectives were tolerability, safety, pharmacokinetic characteristics, immunogenicity, preliminary efficacy. Results: As of January 5, 2024, 100 Chinese subjects with advanced solid tumor were allocated into six cohorts, including 1.2, 1.8, 2.1, 2.4mg/kg and 84, 93mg/m 2 dose levels. Fifty-two subjects with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer (OC) were enrolled and treated with BAT8006 doses of 1.8 mg/kg (n = 2), 2.1 mg/kg (n = 16), 2.4 mg/kg (n = 15), 84mg/m 2 (n = 10) or 93mg/m 2 (n = 9). The median duration of follow-up of these 52 subjects was 4.5 (1.1, 16.4) months. There was 1 dose-limiting toxicity, Grade 4 thrombopenia, reported in 2.4 mg/kg dose cohort in the dose escalation study. The maximum tolerated dose has not yet been reached. In 52 subjects with OC, at least one treatment-emergent adverse events (TEAEs) were reported in 49/52 (94.2%) subjects who have received at least one dose of BAT8006. The most common TEAEs (≥20%) of any grade were thrombocytopenia, neutropenia, anemia, leukopenia, nausea, vomiting and constipation. The majority of the TRAEs were Grade 1 or 2; 57.7% subjects experienced Grade 3 or greater AEs as the worst grade, including thrombocytopenia 11/52 (21.2%), neutropenia 15/52 (28.8%), anemia 11/52 (21.2%), leukopenia 15/52 (28.8%). In the 84 and 93mg/m 2 dose cohorts, which were selected to be further explored in the dose expansion study, the incidences of ≥ Grade 3 thrombocytopenia and neutropenia were 0% vs 22.2% and 30% vs 33.3%, respectively. Three subjects (3/52, 5.8%) experienced dose reduction, and 11 (11/52, 21.2%) subjects had study drug interruption during the study. One (1/52, 1.9%) subject terminated the study treatment due to TEAE. There was one case of death reported during the study due to neoplasm progression. In these 52 subjects, 60.0% of them (31/52) had undergone>3 lines prior systemic treatment. Thirty-six of them have at least one tumor assessment. The ORR per investigator including unconfirmed partial response (PR) is 41.7% (15/36), regardless of the FRα expression. The disease control rate (DCR) is 86.1% (31/36). In 25 subjects with FRα TPS≥50%, the ORR is 11/25 (44.0%), DCR is 22/25 (88.0%). In 12 subjects with FRα TPS≥75%, the ORR is 6/12 (50.0%), DCR is 22/25 (91.7%). Conclusions: BAT8006 was well-tolerated with manageable toxicity and demonstrated preliminary antitumor activity in ovarian cancer. Clinical trial information: NCT05378737 .