biomarkersBiomarker

c-Met protein overexpression (IHC 3+ in >= 50% of tumour cells)

aka c-Met overexpression, MET overexpression, c-Met high, MET IHC 3+, c-Met protein overexpression, MET SP44, c-Met-high NSCLC

c-Met overexpression is a stain, not a gene change: strong (3+) membrane staining in at least half of tumour cells. It selects telisotuzumab vedotin, an antibody-drug conjugate, in previously treated non-squamous lung cancer.

The VENTANA MET (SP44) RxDx Assay scores c-Met protein on tumour cell membranes and cytoplasm; the telisotuzumab vedotin (Emrelis, May 2025) label defines high c-Met overexpression as 50 percent or more of tumour cells with strong (3+) staining, as determined by an FDA-approved test, in locally advanced or metastatic non-squamous NSCLC after prior systemic therapy (LUMINOSITY). About a quarter of non-squamous, EGFR wild-type lung cancers meet the bar. Overexpression can occur without amplification or exon 14 skipping and the three readouts are scored separately.

Part ofMET· METOther readoutsMET amplification MET exon 14 skipping mutation All readouts

MET: 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 receptor that is either mutated in some lung cancers or amplified as an escape route when other lung cancer drugs fail.

IHC score 1 approval threshold

What it means for a patient

If the SP44 stain shows strong c-Met in at least half of your non-squamous lung cancer cells, telisotuzumab vedotin is on label after a first treatment has stopped working. This is a protein stain, so a sequencing report that says nothing about MET does not answer the question; ask whether the stain was done.

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

50 percent or more of tumour cells showing strong (3+) membranous and/or cytoplasmic c-Met staining on the VENTANA MET (SP44) RxDx Assay.

“MET protein expression (>= 50% of tumor cells exhibiting strong membrane and/or cytoplasmic staining 3+)”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
>= 50% of tumour cells with strong (3+) staining	Telisotuzumab vedotin	Non-small-cell lung cancer	FDA	label

Drugs whose label names it

Telisotuzumab vedotin

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
VENTANA MET (SP44) RxDx Assay	Ventana Medical Systems (Roche Tissue Diagnostics)	Non-Small Cell Lung Cancer (NSCLC) - Tissue	Telisotuzumab vedotin	P240037 (05/14/2025)

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.