Dong-A ST Advances CLDN18.2-Targeting ADC DA-3501 Into First-in-Human Trial for Gastric and Pancreatic Cancers
South Korean pharmaceutical company Dong-A ST has registered a first-in-human Phase I/IIa clinical trial for DA-3501, a Claudin 18.2-targeting antibody-drug conjugate, in patients with advanced gastric or gastroesophageal junction adenocarcinoma and pancreatic ductal adenocarcinoma. The molecule, originally designated AT-211, was developed by AbTis, a biotech subsidiary Dong-A ST acquired in December 2023, using the proprietary AbClick site-selective conjugation platform. DA-3501 enters clinical testing as the ADC modality continues to attract investment in gastrointestinal oncology, where CLDN18.2 has emerged as a validated target following Astellas's approval of zolbetuximab in 2023. The Dong-A ST clinical trial adds another entrant to a field that now spans naked antibodies, ADCs, and cell therapies directed at this tight junction protein.
The trial (NCT07481357) is an open-label, non-randomized, sequential dose-escalation study enrolling up to 51 patients aged 19 years or older with histologically or cytologically confirmed CLDN18.2-positive disease and measurable tumors per RECIST v1.1. DA-3501 is administered as an intravenous infusion once every three weeks across 11 planned dose levels. The co-primary endpoints are maximum tolerated dose, assessed by dose-limiting toxicities during the first 21-day cycle, and optimal biological effective dose, determined by overall response rate at 42 days. Secondary endpoints were not specified in the registration. Eligibility requires a life expectancy of at least 12 weeks; patients with cardiac or gastrointestinal abnormalities, active systemic infections, or known hepatitis B, hepatitis C, or HIV are excluded. The trial is registered in South Korea with an estimated start date of Q1 2026, primary completion in Q1 2028, and full completion by Q1 2029. No FDA regulatory pathway has been disclosed; the study is not listed as an FDA-regulated drug trial.
CLDN18.2 is a tight junction protein whose expression in healthy tissue is confined to differentiated gastric mucosal cells. In malignancy, it is aberrantly overexpressed on tumor cell surfaces in approximately 77% of gastric cancers and a subset of pancreatic ductal adenocarcinomas, creating a therapeutic window for targeted agents. DA-3501 exploits this by coupling an anti-CLDN18.2 monoclonal antibody to a cytotoxic payload via AbTis's AbClick linker, a third-generation site-specific conjugation technology that enables controlled drug-antibody ratios without requiring antibody engineering. The specific payload class has not been disclosed. Upon binding CLDN18.2, the ADC is internalized and the linker is cleaved intracellularly, releasing the cytotoxin. Preclinical work on CLDN18.2-targeting ADCs has demonstrated tumor regression in xenograft models. AbTis was founded in 2016 by Sang Jeon Chung and validated its platform through collaborations with Lonza and WuXi XDC before Dong-A ST's full acquisition. The molecule was developed entirely in-house within the Dong-A ST corporate family, with no disclosed in-licensing arrangement. Research on CLDN18.2 as a therapeutic target continues to expand across multiple modalities.