Abstract CT094: A Phase 1/2 study of BDC-4182, a claudin18.2-targeting next generation immune-stimulating antibody conjugate (ISAC), in patients with advanced gastric and gastroesophageal cancer

Abstract Background: Claudin 18. 2 (CLDN18. 2) is a transmembrane tight junction protein with expression restricted to the gastric mucosal epithelia where CLDN18. 2 protects against paracellular acid leakage and associated gastritis. 1 CLDN18. 2 overexpression has been observed in several tumor types, including gastric, esophageal, and pancreatic cancer. 2, 3 Loss of cell polarity in these tumors results in CLDN18. 2 localization to surfaces that are more readily accessible to biologics and effector cells. This expression pattern makes CLDN18. 2 a compelling target for immune-stimulating antibody conjugates (ISACs) that combine the specificity of tumor-targeting antibodies with the potency and durability of immune activation. BDC-4182 is a next-generation ISAC consisting of a CLDN18. 2-targeting antibody covalently attached to a novel toll-like receptor (TLR) 7/8 agonist via a non-cleavable linker. In preclinical models, systemic delivery of ISACs has been shown to broadly activate the innate and adaptive immune system, leading to complete tumor regression. A BDC-4182 surrogate induced immunologic memory and epitope spreading as evidenced by rejection of tumor cells that no longer express the target antigen (CLDN18. 2) following re-challenge. 4, 5 Methods: This is a first-in-human Phase 1 dose escalation and Phase 2 expansion study of BDC-4182. Up to 122 patients with advanced gastric and gastroesophageal cancer will be enrolled. To optimize tolerability, BDC-4182 is administered via an intra-patient step-up dosing regimen wherein subjects receive lower initial priming doses prior to the target dose. Primary objectives are to define safety and tolerability and to determine the recommended phase 2 dose (RP2D) of BDC-4182 as a single agent. Secondary objectives will evaluate the preliminary anti-tumor activity of BDC-4182, analyze PK characteristics of BDC-4182, and evaluate the immunogenicity of BDC-4182 as a single agent. Exploratory analyses will also be conducted to explore potential biomarkers in blood and tumor tissue associated with exposure, efficacy, or safety of BDC-4182, and to define CLDN18 expression in tumor tissue. This study is being conducted in Australia, South Korea, and Taiwan. References: 1. Suzuki K, Sentani K, Tanaka H, et al. Cell Mol Gastroenterol Hepatol. 2019;8: 119-142. 2. Hong JY, An JY, Lee J, et al. Transl Cancer Res. 2020;9: 3367-3374. 3. Chen J, Xu Z, Hu C, et al. Front Oncol. 2023;13: 1132319. 4. Fu C, Luo A, Liu J, et al. J Immunother Cancer. 2024;12 (Suppl 2): Abstract 1052. 5. Kim HK, Monnier J, Fu C, et al. J Immunother Cancer. 2023;11 (Suppl 1): Abstract 1147-D. Citation Format: Sophia Frentzas, Michelle Morris, Megan Barnet, Niall Tebbutt, Mark Wong, Michael Michael, Hyung-Don Kim, Keun-Wook Lee, Sun Young Rha, Sang Cheul Oh, I-Chen Wu, Li-Yuan Bai, Wen-Chi Chou, Ming-Huang Chen, Yen-Yang Chen, Chia-Chi Lin, Anthony Rodrigues, Jason Ptacek, Michael N. Alonso, Tariq Arshad, Jakob Dupont, Kristi Balacy, Sung Hee Lim. A Phase 1/2 study of BDC-4182, a claudin18. 2-targeting next generation immune-stimulating antibody conjugate (ISAC), in patients with advanced gastric and gastroesophageal cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT094.