Phase 1b/2 ASP546C CLDN18.2-targeted ADC with topoisomerase I inhibitor payload

Astellas Pharma Global Development is running this Phase 1b/2, open-label, multicohort study to define a tolerable, active dose and characterize safety/PK plus preliminary efficacy of ASP546C. ASP546C is an antibody–drug conjugate (ADC) that binds claudin 18.2 (CLDN18.2) on tumor cells and delivers a topoisomerase I inhibitor payload, aiming to concentrate DNA-damaging cytotoxicity in CLDN18.2-expressing tumors. Part 1 enrolls unresectable locally advanced/metastatic gastroesophageal adenocarcinoma (gastric/GEJ/esophageal) and compares lower vs higher dose; cohorts 1–2 also focus on HER2-positive disease (a clinically important subset where dual-biomarker selection may sharpen benefit/risk). Part 2 gives the higher dose in pancreatic adenocarcinoma (cohort 3) and a pan-tumor basket (cohort 4: cholangiocarcinoma, colorectal adenocarcinoma, NSCLC adenocarcinoma, SCLC, ovarian mucinous carcinoma, and invasive breast cancer), all requiring CLDN18.2 expression and at least one prior systemic line. Today’s care in these post–first-line settings is typically sequential systemic therapy (fluoropyrimidine/platinum ± trastuzumab and/or immunotherapy for gastroesophageal cancer; gemcitabine/nab-paclitaxel or FOLFIRINOX-derived regimens for pancreatic cancer; and tumor-specific chemo/targeted/immunotherapy options), so the key angle is whether CLDN18.2-directed ADC delivery can extend the emerging CLDN18.2 biomarker beyond antibodies into a broader, cross-tumor ADC strategy.