ideasIdea
Biomarker-directed first-line quadruplets in gastric cancer
Stomach cancer now has three add-on biomarkers (HER2, PD-L1, Claudin 18.2) that often overlap. Test whether combining two add-ons beats picking one.
About 20% of CLDN18.2-positive tumours are PD-L1 CPS ≥5; HER2 and CLDN18.2 rarely overlap. Chemotherapy + zolbetuximab + nivolumab is under study (ILUSTRO cohorts); HERIZON-GEA-01 already combined zanidatamab with tislelizumab.
Hypothesis
In CLDN18.2-positive, PD-L1 CPS ≥5 tumours, chemotherapy + zolbetuximab + PD-1 blockade improves OS over chemotherapy + PD-1 alone without prohibitive toxicity.
Rationale
Non-overlapping mechanisms (ADCC vs T-cell release); zolbetuximab-induced cell death may increase antigen presentation.
What would test it
Randomised phase 3 in double-positive patients; OS primary; ctDNA and CLDN18.2 heterogeneity as stratifiers.
Maturity
early clinical