T320 tissue factor-targeted ADC from pre-clinical research to phase I clinical study.

Abstract

e15032 Background: Tissue factor (TF) is highly expressed in various malignant tumors, including pancreatic, cervical, lung, and esophageal cancers, while being minimally expressed in normal tissues. T320 is a novel antibody-drug conjugate (ADC) consisting of a TF-targeting humanized monoclonal IgG1 conjugated with the cytotoxic payload monomethyl auristatin E (MMAE). Methods: Preclinical evaluation included in vitro binding affinity assays using TF-expressing tumor cell lines and in vivo efficacy studies in multiple human tumor xenograft models to assess tumor growth inhibition. GLP-compliant toxicology and safety studies were conducted in cynomolgus monkeys, administering T320 at doses up to 5 mg/kg weekly for five weeks (QWx5W) to evaluate systemic toxicity. Based on these GLP non-clinical studies, a non-randomized, open-label, multicenter Phase I clinical study was launched to evaluate the safety, tolerability, and pharmacokinetics (PK) of T320 in patients with advanced solid tumors. Results: In vitro studies demonstrated that T320 has a high affinity for its tumor cell target. In vivo efficacy studies showed over 90% inhibition of tumor growth, and toxicology studies in monkeys revealed no serious systemic toxicity at doses up to 5 mg/kg QWx5W. As of December 2025, 9 patients have been enrolled in the Phase I study. Preliminary clinical PK analysis and adverse drug reactions (ADRs) have been assessed; notably, one patient with ovarian cancer in the 0.4 mg/kg Q3W cohort achieved durable stable disease for 6 months. The most common ADRs (occurring in at least 20% of patients) included hypoalbuminemia, anemia, increased blood bilirubin, gastrointestinal bleeding, coagulation disorder, constipation, nausea, and fatigue. Conclusions: Preclinical studies have demonstrated the potent anti-tumor efficacy and favorable pharmacokinetics and safety profile of T320. Early clinical data indicate manageable toxicity and promising activity, specifically highlighted by the durable stable disease observed in ovarian cancer. Further evaluation of T320 performance in the ongoing Phase I clinical study is expected.