Phase 1 XNW28012 tissue factor–targeted topo1 inhibitor ADC in metastatic pancreatic cancer

Evopoint Biosciences’ Phase 1, open-label, randomized, multicenter study tests XNW28012 monotherapy in metastatic pancreatic cancer that has progressed after prior therapy, with two IV Q3W dose levels (2.0 mg/kg vs 2.4 mg/kg). XNW28012 is an antibody-drug conjugate that binds tissue factor (TF) on tumor cells, internalizes, and releases a topoisomerase 1 inhibitor payload to induce DNA damage and cell death. The primary focus is safety/tolerability with pharmacokinetics, immunogenicity (anti-drug antibodies), and preliminary antitumor activity (e.g., response rate, duration of response, PFS) to support dose selection for later studies. TF is broadly expressed across many epithelial tumors and can be prevalent in pancreatic cancer, making TF an attractive “address label” for ADC delivery rather than a rare biomarker-defined niche. For patients whose metastatic disease has already progressed, today’s care is sequential systemic therapy—commonly fluoropyrimidine- and gemcitabine-based combinations (with irinotecan/oxaliplatin used across lines) and targeted options only for small molecular subsets (e.g., BRCA/PALB2, MSI-high)—so this program explores whether a TF-directed topo1 ADC can add a new post-progression option.