Les fusions NRG1 se produisent dans environ 0,5% d'adénocarcinome ductal pancréatique (PDAC) - un a...
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| ID | BMA-NRG1-FUSION-PDAC |
|---|---|
| Type | Pertinence thérapeutique |
| État | reviewed 2026-05-03 | pending_clinical_signoff | actionability review required |
| Maladies | DIS-PDAC |
| Sources | SRC-ESMO-PANCREATIC-2024 SRC-NCCN-PANCREATIC-2025 |
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| Biomarqueur | BIO-NRG1-FUSION |
|---|---|
| Variante | fusion de gène NRG1 — tout partenaire de fusion (RBPMS-NRG1, SLC3A2-Nrga1, PMEPA1-Nrg1 parmi les plus fréquents dans le PDAC; détecté par ARN-seq) |
| Maladie | DIS-PDAC |
| Niveau ESCAT | IIA |
| Combinaisons recommandées | zenocutuzumab 750 mg IV q2w monotherapy (post-gemcitabine-based or post-FOLFIRINOX; CRESTONE regimen) |
| Résumé des faits | NRG1 fusions occur in ~0.5% of pancreatic ductal adenocarcinoma (PDAC) — a rare but actionable subset. Zenocutuzumab (MCLA-128), anti-HER2/HER3 bispecific antibody, FDA accelerated approval (Nov 2024) for NRG1 fusion-positive locally advanced or metastatic NSCLC and pancreatic adenocarcinoma after prior systemic therapy. CRESTONE trial (Schram et al. JCO 2024): NRG1-fusion PDAC cohort — ORR 40%, mDOR 9.1 mo, mPFS 8.7 mo — particularly notable given the ~3 mo mPFS typically seen with 2L-3L chemotherapy in PDAC. NRG1-fusion PDAC is likely KRAS-wild-type in >90% of cases (oncogenic KRAS and NRG1 fusion may be functionally redundant). RNA sequencing required — DNA NGS panels miss most NRG1 fusions. |
Notes
ESCAT IIA (accelerated approval based on ORR; confirmatory data pending). NRG1-fusion PDAC is enriched in KRAS-wild-type tumors (testing KRAS early identifies a subpopulation that warrants comprehensive RNA-seq). ORR of 40% in CRESTONE PDAC cohort is particularly impactful given the absence of other effective targeted therapies in 2L-3L PDAC. Testing strategy: if KRAS-wild-type PDAC identified, proceed to RNA-based comprehensive genomic profiling to detect NRG1 (and other rare fusions: NTRK, ALK, RET, FGFR). Zenocutuzumab is generally well tolerated: infusion reactions (premedication required), fatigue, nausea; no grade 3-4 cardiotoxicity seen in CRESTONE.
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