Abstract CT165: A phase 1/2a, multicenter, open-label, first-in-human study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DB-1311 (a B7-H3-targeting ADC) in patients with advanced/metastatic solid tumors

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Abstract Background: B7 homolog 3 protein (B7-H3, an immune checkpoint molecule) overexpression correlates with disease progression and poor prognosis in various cancers, including lung cancer, esophageal cancer, prostate cancer, and melanoma, is therefore as an ideal candidate for targeted immunotherapy. DB-1311 is an antibody-drug conjugate (ADC) comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody covalently linked to a proprietary DNA topoisomerase I inhibitor via a maleimide tetrapeptide-based cleavable linker, with a drug-to-antibody ratio of approximately 6. Preclinical studies of DB-1311 demonstrated promising antitumor activity in solid tumors and a tolerable safety profile, warranting further clinical development. Methods: This global, first-in-human, Phase 1/2a study includes dose escalation and expansion parts to assess the safety, tolerability, pharmacokinetics, and antitumor activity of DB-1311 in patients (pts) with pretreated advanced/metastatic solid tumors (NCT05914116). Eligible pts must have tumor that has relapsed or progressed on or after standard systemic treatments, or is intolerable with standard treatment, or for which no standard treatment is available; have ECOG PS ≤1; and evidence adequate organ function. Up to 5 ascending dose levels of DB-1311 will be evaluated with an accelerated titration at first dose followed by a classic “3+3” design to identify the maximum tolerated dose and/or recommended phase 2 dose in pts with solid tumors. Phase 2a part will initiate with a randomization (1:1) cohort for dose optimization in pts with small cell lung cancer with two dose levels identified by the safety monitoring committee based on cumulative data from Phase 1 part. The other five cohorts will enroll pts with non-small cell lung cancer, esophageal squamous cell carcinoma, castration-resistant prostate cancer, melanoma, and other solid tumors at the dose level(s) determined based on cumulative data. DB-1311 will be administrated intravenously as monotherapy until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of consent. The study plans to enroll approximately 90 pts in Phase 1 and 190 in Phase 2a from locations including but not limited to Australia, United States, China, and Taiwan. To the data cut-off 05 Dec 2023, 11 pts have been enrolled in the study. Citation Format: Ying Cheng, Aaron Lisberg, Charlotte Lemech, Afaf Abed, Arvind Chaudhry, Andrew Schmidt, Xin Lu, Zhongyuan Zhu, Wei Gu, Yang Qiu, Rong Shi, Bin Zhang. A phase 1/2a, multicenter, open-label, first-in-human study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DB-1311 (a B7-H3-targeting ADC) in patients with advanced/metastatic solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT165.