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A rare fusion that joins the neuregulin 1 gene to a partner, leaving the HER3 ligand stuck on the cell surface where it switches HER3 on continuously. It is found in a small percentage of lung adenocarcinomas, particularly invasive mucinous adenocarcinoma in people who have never smoked, and in pancreatic and biliary cancers, and zenocutuzumab is approved for it.
NRG1 encodes neuregulin 1, the ligand of HER3. A fusion (CD74::NRG1 and SLC3A2::NRG1 are the commonest partners) keeps the EGF-like domain of neuregulin tethered to the membrane, where it drives HER2-HER3 dimerisation and downstream signalling; the readout is filed under HER3 for that reason, and it is why a HER2 by HER3 bispecific antibody treats it. The fusions are rare, enriched in invasive mucinous adenocarcinoma of the lung and in people who have never smoked, and they are missed by DNA-only panels often enough that RNA sequencing is the recommended way to look for them. Zenocutuzumab (Bizengri) was approved by the FDA under accelerated approval on the basis of overall response rate and duration of response, for advanced unresectable or metastatic NRG1 fusion-positive non-small cell lung cancer and pancreatic adenocarcinoma after progression on prior systemic therapy, with cholangiocarcinoma added to the label in May 2026. No companion diagnostic is listed on the FDA device list for it; the label asks only that patients be selected on the presence of an NRG1 gene fusion in tumour specimens.
In plain words · HER3 is a cousin of HER2 that cancers use as an escape route when HER2 or EGFR are blocked.
An NRG1 fusion is rare and easy to miss, and it opens a treatment that nothing else does: zenocutuzumab is approved for advanced lung, pancreatic and bile duct cancers that carry one, after other treatment has stopped working. Ask whether the panel your tumour was tested on included RNA sequencing, because DNA-only panels miss many NRG1 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.
An in-frame fusion involving NRG1 detected in a tumour specimen, best by RNA sequencing because DNA-only panels miss many of these rearrangements.
“Select patients for treatment with BIZENGRI based on the presence of an NRG1 gene fusion in tumor specimens”
BIZENGRI (zenocutuzumab) prescribing information, section 2.1 Patient Selection (DailyMed, revised May 2026)| Threshold | Drug | Cancer | Regulator | Source |
|---|---|---|---|---|
| NRG1 gene fusion in a tumour specimen | Zenocutuzumab | Non-small-cell lung cancer | FDA | label |
| NRG1 gene fusion in a tumour specimen | Zenocutuzumab | Pancreatic ductal adenocarcinoma | FDA | label |
| NRG1 gene fusion in a tumour specimen | Zenocutuzumab | Biliary tract cancer (cholangiocarcinoma) | FDA | label |
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.
It put a number on how rare NRG1 fusions are and showed that heterogeneous partners make RNA-based testing the only reliable way to find them, which is the practical argument for adding a fusion panel to a driver-negative lung cancer work-up.
It identified a driver in the one lung histology that had none, and it defined a mechanism, ligand presentation, that requires an antibody against the receptor pair rather than a kinase inhibitor.
Shares ROS1 fusion (ROS1-positive), RET fusion and RET mutation, NTRK1/2/3 gene fusion, Gene fusion and the tags biomarker, fusion.
Shares Gene fusion, Receptor tyrosine kinase activation, Comprehensive genomic profiling, Non-small-cell lung cancer and the tag biomarker.
Shares Receptor tyrosine kinase activation, Comprehensive genomic profiling, Non-small-cell lung cancer and the tag biomarker.
Shares Zenocutuzumab, NRG1, HER3, Tumour-agnostic (tissue-agnostic) approval.
Shares HER2 (ERBB2) activating mutation, Non-small-cell lung cancer and the tag biomarker.
Shares Gene fusion, Biliary tract cancer (cholangiocarcinoma) and the tag biomarker.
Shares HER2 (ERBB2) activating mutation, HER2 and the tag biomarker.
Shares Tumour-agnostic (tissue-agnostic) approval, Biliary tract cancer (cholangiocarcinoma), Pancreatic ductal adenocarcinoma and the tag biomarker.