Novel Bispecific Yields Safety, Activity Across Tumor Types

Findings from a phase 1 dose-escalation trial (NCT05808634)¹ evaluating BA3182 revealed a manageable safety profile with preliminary evidence of antitumor activity in patients with treatment-refractory adenocarcinoma. Results were presented during the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Asia Congress 2025.²

“Primary objectives include safety, tolerability, PS3000 - iStock and defining the recommended phase 2 dose,” lead author Jennifer Valerin, MD, PhD, said in a presentation of the data. “Secondary objectives included characterization of antitumor activity, pharmacokinetics, and immunogenicity,” Valerin, an assistant clinical professor, Division of Hematology/Oncology, University of California, in Orange, continued.

The current presentation evaluated subcutaneous doses that ranged from 0.32 mg to 1.2 mg. “When administered subcutaneously, the Cmax [maximum serum concentration] was 2 to 6 times lower with sufficient exposure, but [we] anticipated lower rates of cytokine release syndrome [CRS],” Valerin said. “We have therefore decided to continue forward with the subcutaneous administration. This presentation focuses on the subcutaneous dosing,” she explained.

Investigators explored dose levels of 0.32 mg, 0.1 mg, 0.3 mg, 0.6 mg, and 1.2 mg, with a planned dosing greater than 1.8 mg to 10 mg. As of June 20, 2025, the data cutoff, 22 patients were treated per subcutaneous protocol.

The intravenous (IV) dosing cohort was previously described, and investigators reported a high bioavailability of 76.8%.³

The mean age in the subcutaneous cohort was 58 years, and 50% of patients were male. Most patients (59%) had an ECOG performance status of 0, and 41% had a status of 1. Patients were heavily pretreated and had a median of 3 previous lines of therapy prior to enrollment.

The majority of patients had colon/rectum cancer (11/22; 50%), followed by pancreatic cancer (6/22; 27%). The remaining patients had adenoid cystic carcinoma; cholangiocarcinoma; and gallbladder, lung, and ovarian cancer, all of which were 5%.

Safety and Antitumor Activity

Regarding safety, the most frequent treatment- related adverse events (TRAEs) of any grade were transient and manageable. These TRAEs were mainly grade 1 or 2 and occurred during the priming-dose phase.

Overall, 20 (91%) patients exhibited anygrade AEs, 6 (32%) exhibited grade 3, and 1 (5%) patient exhibited a grade 4 AE.

No AEs led to treatment discontinuation or death.

Specific AEs of note include elevated alanine aminotransferase levels (any grade, 36%; grade 3 or higher, 14%), elevated aspartate aminotransferase levels (32%; 14%), and nonfebrile neutropenia (14%; 9%).

Valerin highlighted the experience of a 71-year-old man with intrahepatic cholangiocarcinoma with a 13% reduction in his tumor at a low dose of 0.1 mg of BA3182 after 12 weeks. The patient had been previously treated in a clinical trial with the standard of care: gemcitabine, cisplatin, durvalumab (Imfinzi), and an investigational agent.

“This patient has experienced tumor reduction and is asymptomatic after 2 months on treatment. He has resumed activities of daily living while being on study. The patient has increased dosage to 2.3 mg,” Valerin said.

Mechanism of Action and Ongoing Research

BA3182 is a bispecific T-cell engager that selectively binds to EpCAM and CD3. BA3182’s binding to EpCAM is greatly reduced or eliminated in healthy tissues, thus limiting on-target, off-tumor activity.

Preclinical studies showed potent antitumor activity in colorectal and breast cancer models, with a greater than 100-fold improvement in therapeutic index over nonconditionally binding EpCAM x CD3 T-cell engagers.

“BA3182 binds EpCAM and CD3 in a low pH environment, thus restricting beneficial cytolytic immune synapses to the tumor microenvironment while avoiding damage to normal EpCAM-expressing tissues,” Valerin said. “Adverse events, including CRS, were generally low grade, transient, and manageable.

"In the subcutaneous dose, no instances of CRS were observed, suggesting that the therapeutic window targeting EpCAM may be meaningfully widened. Dose escalation actively continues to focus on colorectal cancer,” she concluded.

REFERENCES:

1. Valerin JB, Thomas JS, Selfridge JE, et al. First-in-human phase 1 study of a dual-conditionally active biologic (CAB) EpCAM x CD3 bispecific T-cell engager (TCE), BA3182, in patients with treatment refractory metastatic adenocarcinoma. Ann Oncol. 2025;10(suppl 6):1-7. doi:10.1016/esmoop/ esmoop105384

2. Valerin JB, Thomas JS, Selfridge JE, et al. First-in-human phase 1 study of a dual-conditionally active biologic (CAB) EpCAM x CD3 bispecific T-cell engager (TCE), BA3182, in patients with treatment refractory metastatic adenocarcinoma. Presented at: ESMO TAT Asia Congress 2025; July 18-20, 2025; Hong Kong SAR, China. Abstract 360.

3. Starodub A, Thomas J, Selfridge JEE, et al. Preliminary results from a first-in-human phase I study of a dual-conditionally binding EpCAM x CD3 bispecific T-cell engager, BA3182, in pts with treatment refractory metastatic adenocarcinoma. Ann Oncol. 2025;36(suppl 1):S183-S184. doi:10.1016/ annonc/annonc1826