NRG1 (neuregulin-1) gene fusion in NSCLC — predominant in invasive mucinous adenocarcinom...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`RF-NSCLC-NRG1-FUSION-ZENO-CANDIDATE`
Type	Red flag
Status	reviewed 2026-04-29 \| pending_clinical_signoff
Diseases	`DIS-NSCLC`
Sources	`SRC-ESMO-NSCLC-METASTATIC-2024` `SRC-NCCN-NSCLC-2025`

Red Flag Origin

Definition	NRG1 (neuregulin-1) gene fusion in NSCLC — predominant in invasive mucinous adenocarcinoma (~7-27% of KRAS-WT IMA). NRG1 fusions produce aberrant ligand-display driving HER2-HER3 heterodimer signalling. Zenocutuzumab (MCLA-128, Bizengri) — first-in-class HER2 × HER3 bispecific IgG1 — granted FDA accelerated approval 4 Dec 2024 for advanced NSCLC and pancreatic NRG1+ post-prior systemic therapy. eNRGy phase-2 (Schram 2024; n=204): NSCLC ORR 33%, mDOR ~9 months. RNA-NGS testing critical — DNA-only panels miss fusions in 30-40% of cases. Candidate RF until pivotal trial-Source SRC-ENRGY-SCHRAM-2024 ingested.
Clinical direction	intensify
Category	high-risk-biology
Shifts algorithm	ALGO-NSCLC-METASTATIC-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "nrg1_fusion",
      "value": true
    },
    {
      "finding": "nrg1_status",
      "value": "fusion-positive"
    },
    {
      "finding": "nrg1_rearrangement",
      "value": "positive"
    }
  ],
  "type": "biomarker"
}

Notes

Candidate RF — eNRGy trial-Source not yet ingested (SRC-ENRGY-SCHRAM-2024 flag for ingestion chunk). Routes 2L+ to zenocutuzumab 750 mg IV every 2 weeks. Highest NSCLC prevalence in invasive mucinous adenocarcinoma (~7-27% KRAS-WT IMA); rare in conventional adenocarcinoma. Testing methodology critical — RNA-NGS preferred (Archer FusionPlex, Oncomine Comprehensive Plus, FoundationOne CDx with RNA add-on). DNA-only panels report 30-40% false-negative rate due to NRG1 large-intron breakpoint variability. Reflex RNA-NGS recommended at progression in KRAS-WT IMA-NSCLC and KRAS-WT pancreatic. Priority 60 sits with other NSCLC fusion RFs (ALK 50, ROS1 50, RET 50, NTRK 50) — slightly lower because zenocutuzumab is 2L (post-prior systemic therapy per FDA accelerated approval label), not 1L.

Used By

No reverse references found in the YAML corpus.