Phase 1 study of BAT8006, a folate receptor α antibody drug conjugate with strong bystander effect, in subjects with advanced solid tumors.
Authors: Haiyan Jia, Songling Zhang, Yuping Sun, Huifeng Zhang, Jihong Liu, Zhentong Wei, Hong Zhang, Jiajia Mai, Hui Qiu, Jianying Huang, Yehui Shi, Juncheng Wei, Qunxian Rao, Li Sun, An Lin, Jie Tang, Ziyi Fu, Xinlang Zhang, Di Zhong, Jin-Chen Yu
Journal: Journal of Clinical Oncology (2024)

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&gt;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 .