BioAtla presented encouraging first-in-human Phase 1 data for BA3182, a dual-conditionally active bispecific T-cell engager, at the European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress in Barcelona, Spain. The novel therapy demonstrated tumor reductions across multiple adenocarcinoma types in heavily pretreated patients with treatment-refractory metastatic disease.
Phase 1 Trial Design and Patient Population
The ongoing dose-escalation clinical trial enrolled 39 patients with heavily pretreated metastatic adenocarcinoma as of June 20, 2025. Patients had received a median of 3 prior lines of therapy, representing a challenging population with limited treatment options. The trial tested doses ranging from 0.0026 mg to 0.6 mg BA3182 administered weekly, with either 0, 1, or 2 priming doses delivered four to seven days prior to treatment dosing.
Tumor types included a diverse range of adenocarcinomas: adenoid cystic carcinoma, breast, cholangiocarcinoma, colorectal, esophagus, gallbladder, lung, ovarian, and pancreas. Colorectal carcinoma patients constituted 56% of enrolled participants, reflecting the high prevalence of this cancer type among adenocarcinomas.
Promising Efficacy Signals
Five patients achieved objective tumor size reductions across different cancer types: colorectal carcinoma patients experienced 8% and 10% reductions, breast adenocarcinoma showed an 11% reduction, cholangiocarcinoma demonstrated a 13% reduction, and non-small cell lung cancer achieved a notable 25% reduction.
Particularly encouraging were the prolonged progression-free intervals observed in two colorectal carcinoma patients, lasting 11 months and 14 months respectively. These extended periods of disease control in heavily pretreated patients suggest meaningful clinical benefit from BA3182 therapy.
Safety Profile and Administration
The safety profile proved reassuring, with adverse events generally characterized as low-grade, transient, and readily manageable. The trial compared intravenous (IV) and subcutaneous (SC) formulations, with 17 patients receiving IV doses of 0.0026 mg to 0.032 mg weekly and 22 patients receiving SC doses of 0.032 mg to 0.6 mg weekly.
Subcutaneous dosing demonstrated an improved pharmacokinetic profile compared to IV administration, showing delayed and lower maximum concentration with similar trough concentrations. This finding supports the continued development of the SC formulation for patient convenience and potentially improved tolerability.
Cytokine Release Syndrome occurred only with IV dosing prior to implementing prophylactic tocilizumab for the first treatment dose, affecting three patients with Grade 1 (n=2) and Grade 2 (n=1) severity that readily resolved. Early, transient, asymptomatic hepatic transaminase elevations (Grade 1 to Grade 3) occurred in eight patients total across both IV and SC dosing but resolved without delaying subsequent weekly treatment doses.
Dual-CAB Technology Platform
BA3182 represents a novel approach to bispecific T-cell engagement through BioAtla's proprietary Conditionally Active Biologic (CAB) platform technology. The therapy contains two binding sites for EpCAM (Epithelial Cell Adhesion Molecule) and two binding sites for CD3ε, designed to bind their respective targets specifically and reversibly under tumor microenvironment conditions while having reduced binding outside the tumor microenvironment.
"BA3182, our dual-CAB EpCAM x CD3 bispecific TCE, was developed to drive maximal binding in the acidic tumor microenvironment, effectively eliminating binding in healthy tissues, and thereby avoiding on-target, off-tumor toxicities observed by others in previous attempts with EpCAM targeting antibodies," said Jay M. Short, Ph.D., Chairman, Chief Executive Officer and co-founder of BioAtla.
Preclinical studies demonstrated the technology's potential, showing potent antitumor activity in a human colorectal carcinoma xenograft model with greater than 100-fold improvement in therapeutic index compared to non-CAB EpCAM x CD3 variants.
Market Potential and Next Steps
EpCAM expression is robust among adenocarcinomas of the colon, stomach, pancreas, biliary tract, lung, breast, prostate, and thyroid, making it a compelling bispecific T-cell engager target when antibody binding can be reliably restricted to the tumor microenvironment. Short noted that "BA3182 has the potential to serve over one million patients globally and could be a best-in-class bispecific TCE for multiple solid tumor types."
Dose escalation continues at 1.2 mg flat dosing via subcutaneous administration, with updated Phase 1 data anticipated in the second half of 2025. The primary objectives focus on characterizing safety and tolerability with escalating doses to determine efficacious doses for guiding the selection of the recommended Phase 2 dose, while secondary objectives include evaluation of preliminary antitumor activity across different cancer types, pharmacokinetics, and potential immunogenicity.
