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The following is a summary of “Efficacy of Zenocutuzumab in NRG1 Fusion–Positive Cancer,” published in the February 2025 issue of The New England Journal of Medicine by Schram et al.
NRG1 fusions drive oncogenesis in multiple solid tumors by activating HER2-HER3 signaling and downstream proliferation pathways.
Researchers conducted a retrospective study on zenocutuzumab in NRG1 fusion–positive tumors. It showed efficacy with mostly low-grade adverse events (AEs).
They conducted a phase 2 study, assigning patients with advanced NRG1 fusion–positive cancer to 750 mg zenocutuzumab IV every 2 weeks. The primary endpoint was overall response, while secondary endpoints included duration of response, progression-free survival (PFS), and safety.
The results showed that 204 patients with 12 tumor types were treated. Among 158 with measurable disease enrolled ≥24 weeks before data cutoff, 30% (95% CI, 23–37) responded. The median response duration was 11.1 months (95% CI, 7.4–12.9), with 19% ongoing. Responses occurred in 29% (27/93, 95% CI, 20–39) of NSCLC and 42% (15/36, 95% CI, 25–59) of pancreatic cancer cases across NRG1 fusion partners. Median PFS was 6.8 months (95% CI, 5.5–9.1). Most AEs were grade 1 or 2, including diarrhea (18%), fatigue (12%), nausea (11%), and infusion reactions (14%). Due to an AE, 1 patient discontinued the treatment.
Investigators found that zenocutuzumab was effective in advanced NRG1 fusion–positive cancer, especially NSCLC and pancreatic cancer, with mainly low-grade AEs.
Source: nejm.org/doi/full/10.1056/NEJMoa2405008
