SHR-A1904 (garetatug rezetecan) CLDN18.2 ADC posts 25.5% ORR in heavily pretreated CLDN18.2+ solid tumors

SHR-A1904 is an investigational claudin-18.2 (CLDN18.2)–targeting antibody–drug conjugate evaluated in a global Phase 1/2a dose-escalation/optimization study in CLDN18.2-expressing relapsed/refractory solid tumors (NCT05277168). As of December 1, 2025, 51 patients were enrolled (GC/GEJC n=41; pancreatic cancer n=9; lung adenocarcinoma n=1); most had ≥2 prior lines (72.5%), and 42 received ≥3.6mg/kg Q3W (24 Asian; 18 non-Asian). Across all patients, ORR was 25.5% with median DoR 5.7 months, median PFS 2.8 months, and median OS 9.8 months—numerically in the ballpark of typical later-line chemo outcomes in unselected GC/GEJ (often ORR ~10–20% and PFS ~2–4 months with options like taxanes/irinotecan ± ramucirumab), while the non-Asian subgroup showed higher ORR 44.4% but with small numbers and wide CIs. Safety was dominated by GI toxicity: TRAEs 94.1% with nausea 66.7% and vomiting 52.9%; Grade ≥3 TRAEs 41.2% and serious TRAEs 17.6%, with 1 DLT (Grade 3 vomiting) at 6.0mg/kg and no treatment-related deaths—important given CLDN18.2 programs (e.g., zolbetuximab) are also notorious for nausea/vomiting.