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INHIBITING RESISTANCE TO IMMUNOTHERAPY IN HEAD&NECK CANCER BY TARGETING NETRIN-1

Obiettivo

NeckNET is a major clinical development initiative aiming to establish a new standard of care for patients with Head & Neck cancer, one of the most devastating indications with poor prognosis at diagnosis and limited therapeutic options. NeckNET focuses on a specific group with immune checkpoint inhibitor (ICI)-secondary resistant and platinum-naïve recurrent/metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC), a severely underserved population with median survival of only ~12 months. After failure of first-line pembrolizumab, the only approved ICI in this setting, patients face rapid deterioration and poor access to clinical trials, since most active HNSCC studies target earlier lines of therapy or biomarker-selected groups. Thus, there is a critical unmet need for strategies to overcome immunotherapy resistance. NeckNET will evaluate NP137, a first-in-class monoclonal antibody targeting netrin-1, a key driver of epithelial-to-mesenchymal transition (EMT) and immune exclusion. By blocking netrin-1 signalling, NP137 restores tumour sensitivity to immunotherapy. NeckNET builds on encouraging results from the exploratory ImmunoNET trial, where NP137 combined with pembrolizumab achieved clinical benefit in 6 of 8 ICI-secondary refractory R/M HNSCC patients, with survival exceeding expectations for this population. Building on this foundation, NeckNET will conduct a multicentre, randomised Phase II trial in ~100 ICI-secondary resistant R/M HNSCC patients who progressed after initial response or ≥6 months disease stabilisation on pembrolizumab. Participants will be randomised to NP137+pembrolizumab versus platinum-based chemotherapy (investigator’s choice). The primary endpoint is overall survival; secondary endpoints include progression-free survival, quality of life, and translational EMT-biomarker analyses. Led by French SME NETRIS Pharma with GORTEC (FR), TTCC (ES) and ULB (BE), NeckNET will deliver a regulator-aligned trial across European centres.

Campo scientifico (EuroSciVoc)

Parole chiave

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Meccanismo di finanziamento

HORIZON-RIA - HORIZON Research and Innovation Actions

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Invito a presentare proposte

(si apre in una nuova finestra) HORIZON-HLTH-2025-01

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Coordinatore

NETRIS PHARMA SAS
Contributo netto dell'UE
€ 4 571 678,75
Indirizzo
RUE LAENNEC 28 BATIMENT CHENEY C CENTRE LEON BERARD
69008 Lyon
Francia
PMI
Sì
Regione
Auvergne-Rhône-Alpes Rhône-Alpes Rhône
Tipo di attività
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Collegamenti
Costo totale
€ 4 671 678,75

Partecipanti (4)