36Phase 1 dose escalation of BA3182, a conditionally binding EpCAM x CD3 bispecific T-cell engager in metastatic adenocarcinoma

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Abstract Background EpCAM (Epithelial Cell Adhesion Molecule) is a cell surface protein overexpressed by most adenocarcinomas. BA3182, a novel dual-conditionally binding EpCAM x CD3 T cell engager (TCE), is designed to selectively bind to both EpCAM and CD3 in the acidic tumor microenvironment (TME). In healthy tissues, binding of BA3182 to both the EpCAM and CD3 receptors is greatly reduced or eliminated, thus avoiding on-target, off-tumor activity. Preclinical studies showed potent antitumor activity in colorectal and breast cancer models, with a > 100-fold improvement in therapeutic index over non-conditionally binding EpCAM x CD3 TCE's. Methods This phase 1 dose escalation study uses a Bayesian Optimal Interval design in treatment refractory adenocarcinoma patients. Patients received weekly intravenous (IV) or subcutaneous doses of BA3182. EpCAM expression in tumor specimens is characterized by immunohistochemistry. Results As of May 9, 2025, 30 pts were enrolled in cohorts ranging from 2.6-300 micrograms total dose of BA3182 administered weekly IV or subcutaneously. Tumor types include colorectal (n=l 7), PDAC (n = 4), breast (n = 2), cholangiocarcinoma (n = 2), esophageal (n=l), gallbladder (n=l), NSCLC (n=l), ovarian (n=l), and small bowel (n=l). Transient and manageable grade 1 (n = 2) and grade 2 (n=l) CRS were observed. Dose escalation continues at weekly subcutaneous doses of 300 micrograms and higher. Tumor reduction (CRC-8% and -10%; breast-11%; NSCLC-25%) has been observed prior to the 100 microgram dose level. Two pts with CRC experienced prolonged progression-free intervals (8 mo ongoing and 14 mo). Conclusions BA3182, a CAB-EpCAM x CAB-CD3 T-cell engager that selectively binds to both EpCAM and CD3 in the acidic TME, is associated with preliminary evidence of anti-tumor activity with acceptable tolerability in humans. Dose escalation continues.

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