With its recent approval in several jurisdictions, oncologists now face the challenge of choosing between zolbetuximab and ICI for first-line treatment of HER2-/CLDN18.2+ G/GEJ adenocarcinomas in dual biomarker-positive tumors that also co-express PD-L1 with CPS ≥1. The gene discussed is CD274; the disease is adenocarcinoma.