A phase 1 study of BAT8007, an anti-nectin-4 monoclonal antibody-exatecan conjugate, in patients with advanced solid tumors.

e16567 Background: BAT8007 is an antibody-drug conjugate targeting Nectin-4. In this phase 1 study, the authors investigated BAT8007 in subjects with advanced solid tumors. Methods: Subjects with advance solid tumor received BAT8007 on day 1 of a 21-day cycle until subject intolerance or disease progression. The study objectives were tolerability, safety, pharmacokinetic characteristics, immunogenicity, and preliminary efficacy. Results: As of January 30, 2024, 16 Chinese subjects with urothelial carcinoma (UC), non-small cell lung cancer (NSCLC), prostatic cancer, esophageal squamous cancer, hepatocellular carcinoma, ovarian cancer were allocated into five cohorts of 0.8, 1.6, 2.4, 3.0, 3.6mg/kg dose levels. The Nectin-4 expression on tumor tissue was not a requirement for eligibility. There was no dose-limiting toxicity observed, the dose escalation beyond 3.6mg/kg is continuing to be explored. The maximum tolerated dose has not yet been reached. In 16 subjects who have received at least one dose of BAT8007, at least one treatment-emergent adverse events (TEAEs) were reported in 13/16 (81.25%) subjects. The most common TEAEs (≥20%) of any grade were anemia, neutropenia, leukopenia, nausea, vomiting, hypoalbuminemia, hypertriglyceridemia and fatigue. The majority of the treatment-emergent adverse events were Grade 1 or 2; 18.75% subjects experienced Grade 3 or greater AEs, including thrombocytopenia 1/16 (6.25%), worsening anemia 1/16 (6.25%), neutropenia 1/16 (6.25%). The gastrointestinal toxicity was mild. There were no subjects terminated the study treatment due to TEAE. No skin, ocular toxicity and interstitial lung disease were reported. Six subjects with UC were recruited and distributed in 0.8mg/kg(n=1), 1.6mg/kg(n=1) and 3.0mg/kg(n=4) cohort. All of them had undergone prior 3-5 lines of systemic treatments including PD-1 antibodies and platinum-based regimens. Four subjects with UC were enrolled, and 2 of them performed one tumor assessment as data cut off. Both of them showed stable disease with target lesion reductions of -14% and -16.3%, respectively. Both of these two UC subjects had been treated with RC48 (disitamab vedotin, an anti-HER2 ADC) treatment prior to this assessment. Additionally, 1 subject with NSCLC achieved a confirmed partial response (target lesion reduction of -61.0%) in 2.4 mg/kg cohort, and is still benefiting from BAT8007. Conclusions: BAT8007 was well-tolerated with manageable toxicity and demonstrated preliminary antitumor activity in urothelial carcinoma and NSCLC. Clinical trial information: NCT05879627 .