Claudin 18.2 expression (>= 75% of tumour cells, moderate to strong)

aka CLDN18.2, Claudin 18.2 positive, CLDN18.2-positive, claudin 18.2 expression, CLDN18 IHC, CLDN18.2 >= 75%

Claudin 18.2 is a tight-junction protein exposed on stomach cancer cells. Zolbetuximab requires at least 75 percent of tumour cells to stain moderately or strongly, the strictest expression threshold in any current label.

Zolbetuximab (Vyloy) is labelled with fluoropyrimidine and platinum chemotherapy for first-line HER2-negative gastric or GEJ adenocarcinoma whose tumours are CLDN18.2 positive as determined by an FDA-approved test; the SPOTLIGHT and GLOW trials and the VENTANA CLDN18 (43-14A) RxDx Assay define positivity as 75 percent or more of tumour cells with moderate to strong membranous staining. About 38 percent of screened patients met the bar. CLDN18.2 ADCs and CAR-T cells in trials use lower or different cut-offs.

Part ofClaudin 18.2· CLDN18 All readouts

Claudin 18.2: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · A tight-junction protein normally hidden in the stomach lining that becomes exposed in gastric and pancreatic cancers.

IHC score 1 approval threshold

What it means for a patient

If at least three quarters of your stomach cancer cells stain moderately or strongly for claudin 18.2, zolbetuximab can be added to first-line chemotherapy, provided the cancer is HER2-negative. A lower percentage does not qualify under the label, though trials of other claudin 18.2 drugs may accept it. Nausea and vomiting during the first infusions are common and expected.

Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.

Scoring rule

75 percent or more of viable tumour cells with moderate to strong membranous CLDN18 staining on the VENTANA CLDN18 (43-14A) RxDx Assay.

“CLDN18.2 positivity (defined as ≥75% of tumor cells demonstrating moderate to strong membranous CLDN18 staining) was determined by immunohistochemistry on gastric or GEJ tumor tissue specimens from all patients with the VENTANA CLDN18 (43‑14A) RxDx Assay performed in a central laboratory.”
VYLOY prescribing information

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
>= 75% of tumour cells with moderate to strong membranous staining	Zolbetuximab	Claudin 18.2-positive gastric cancer	FDA	label

Drugs whose label names it

Zolbetuximab

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
VENTANA CLDN18 (43-14A) RxDx Assay	Ventana Medical Systems (Roche)	Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma - Tissue	Zolbetuximab	P230018 (10/18/2024)

Tests that measure it

VENTANA CLDN18 (43-14A) RxDx Assay

Trials that name this readout

Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.