biomarkersBiomarker

NTRK1/2/3 gene fusion

aka NTRK fusion, NTRK gene fusion, TRK fusion, NTRK1 fusion, NTRK2 fusion, NTRK3 fusion, ETV6-NTRK3, ETV6::NTRK3, TRK fusion cancer, NTRK

An NTRK fusion joins one of three TRK kinase genes to a partner and drives cancers from infant fibrosarcoma to salivary and thyroid tumours, rare in common cancers but near-universal in a few rare ones. Larotrectinib, entrectinib and repotrectinib are approved for it regardless of tumour type.

NTRK1, NTRK2 and NTRK3 fusions (ETV6::NTRK3 in secretory carcinomas and infantile fibrosarcoma, LMNA::NTRK1 and TPM3::NTRK1 elsewhere) are best detected by RNA sequencing; DNA panels miss some NTRK2 and NTRK3 events because of long introns, and pan-TRK immunohistochemistry is a screen that needs molecular confirmation. Larotrectinib (2018) and entrectinib (2019) are labelled tumour-agnostically for solid tumours with an NTRK gene fusion without a known acquired resistance mutation, metastatic or where surgery would cause severe morbidity, with no satisfactory alternative or after progression; repotrectinib (2024) for NTRK fusion-positive solid tumours. FoundationOne CDx and Liquid CDx and TruSight Oncology Comprehensive are the listed companion diagnostics.

Part ofNTRK· NTRK1/2/3 All readouts

NTRK: 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 · Rare gene fusions found across dozens of cancer types; the first target where a drug was approved for any tumour carrying it.

Sequencing 2 approval thresholds

What it means for a patient

If your tumour carries an NTRK fusion, a TRK tablet (larotrectinib, entrectinib or repotrectinib) is on label whatever the type of cancer, once it has spread or cannot be removed without serious harm, and responses are frequent and often long. Ask whether the test included RNA sequencing, because DNA-only panels can miss these fusions.

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

An in-frame fusion involving the kinase domain of NTRK1, NTRK2 or NTRK3 detected by RNA or DNA sequencing (pan-TRK IHC as a screen only), without a known acquired resistance mutation.

“NTRK1, NTRK2 and NTRK3 fusions”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
NTRK gene fusion without a known acquired resistance mutation	Larotrectinib	Metastatic cancer (cancer that has spread)	FDA	label
NTRK gene fusion in tumour or plasma	Entrectinib	Metastatic cancer (cancer that has spread)	FDA	label

Drugs whose label names it

Larotrectinib Entrectinib

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
FoundationOne CDx	Foundation Medicine	Solid Tumors - Tissue	Larotrectinib	P170019/S017 (10/23/2020)
FoundationOne CDx	Foundation Medicine	Solid Tumors - Tissue	Entrectinib	P170019/S014 (06/07/2022)
FoundationOne Liquid CDx	Foundation Medicine	Solid Tumors - Plasma	Entrectinib	P190032/S004 (12/22/2022)
TruSight Oncology Comprehensive	Illumina	Solid Tumors - Tissue	Larotrectinib	P230011 (08/21/2024)

Tests that measure it

FoundationOne CDx FoundationOne Liquid CDx Tempus xT and xT CDx FoundationOne CDx FoundationOne Liquid CDx Caris MI Profile Illumina TruSight Oncology Comprehensive Exact Sciences OncoExTra

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.