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In stomach cancers that express the protein Claudin 18.2, adding the antibody zolbetuximab to chemotherapy extended survival by nearly three months, making Claudin 18.2 a new biomarker to test for.
Double-blind phase 3 trial of 565 patients with untreated, HER2-negative, Claudin 18.2-positive (moderate-to-strong staining in 75% or more of tumour cells) locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma, randomised to zolbetuximab or placebo plus mFOLFOX6. Primary endpoint was PFS.
Median PFS was 10.6 vs 8.7 months (HR 0.75) and median OS 18.2 vs 15.5 months (HR 0.75). Together with the GLOW trial (zolbetuximab plus CAPOX) it led to approvals in 2024 and made Claudin 18.2 testing routine for HER2-negative gastric cancer, while opening a target now pursued by ADCs and CAR-T cells.
Patients with newly diagnosed advanced stomach cancer should now have Claudin 18.2 tested alongside HER2, PD-L1 and mismatch repair, because roughly a third will be eligible for zolbetuximab, which adds about three months of median survival. The main practical problem is nausea and vomiting during infusions, which needs aggressive prophylaxis. How to sequence or combine it with immunotherapy in PD-L1-positive tumours is unresolved.
Shares Yoon-Koo Kang, Kohei Shitara, Claudin 18.2-positive gastric cancer, Claudin 18.2.
Shares Yoon-Koo Kang, Kohei Shitara, ADCC (antibody-dependent cellular cytotoxicity), Claudin 18.2-positive gastric cancer.
Shares Kohei Shitara, Lines of therapy, Progression-free survival (PFS), Overall survival (OS).
Shares Yung-Jue Bang, Kohei Shitara, Oesophageal cancer, Monoclonal antibodies.
Shares Claudin 18.2-positive gastric cancer, Claudin 18.2, Astellas, Gastric & gastro-oesophageal junction cancer.
Shares Claudin 18.2-positive gastric cancer, Claudin 18.2, Immunohistochemistry (IHC), Gastric & gastro-oesophageal junction cancer.
Shares Yung-Jue Bang, Overall survival (OS), Immunohistochemistry (IHC), Gastric & gastro-oesophageal junction cancer.
Shares Lines of therapy, Progression-free survival (PFS), Overall survival (OS), Histopathology & immunohistochemistry.