Zenocutuzumab showed efficacy in patients with advanced NRG1 fusion–positive cancer, including those with non–small cell lung cancer (NSCLC), according to results of a registrational, phase 2 clinical study.
Alison M. Schram, MD, of the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, and colleagues, conducted the study and recently published the findings in The New England Journal of Medicine.
This publication follows the US Food and Drug Administration’s December 2024 action to grant accelerated approval to zenocutuzumab (Bizengri, Merus N.V.) for adults with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma who have an NRG1 gene fusion with disease progression on or after prior systemic therapy.
“This is an effective drug for a disease that doesn’t respond well to standard treatments,” said Stephen V. Liu, MD, of the Georgetown University School of Medicine and Georgetown’s Lombardi Comprehensive Cancer Center in Washington, DC, who was involved with the study published in The New England Journal of Medicine.
Zenocutuzumab, a bispecific antibody directed against HER2 and HER3, is being evaluated in this setting because NRG1 fusions are “recurrent oncogenic drivers found in multiple solid tumors” and NRG1 is known to bind to HER3, “leading to heterodimerization with HER2 and activation of downstream growth and proliferation pathways.”
The study enrolled and treated 204 patients with 12 tumor types, including NSCLC and pancreatic cancer. All patients received 750 mg of zenocutuzumab intravenously every two weeks. The study’s primary endpoint was overall response (complete or partial response), according to investigator assessment. The secondary endpoints included duration of response, progression-free survival (PFS), and safety.
Responses occurred in 30% (95% CI, 23%-37%) of the 158 patients who had measurable disease and were enrolled at least 24 weeks before the data cutoff date. The median duration of response was 11.1 months (95% CI, 7.4-12.9), with 19% of responses ongoing at the data cutoff date. The median PFS was 6.8 months (95% CI, 5.5-9.1).
Among patients with NSCLC, responses occurred in 27 of 93 patients (29%; 95% CI, 20%-39%). Responses were also observed in patients with pancreatic cancer (42%; 95% CI, 25%-59%). The responses were seen in multiple tumor types and across multiple NRG1 fusion partners.
“Having a targeted agent here that’s effective is long overdue,” Dr. Liu said.
Adverse events were “primarily grade 1 or 2,” with the most common adverse events “that were considered by the investigator to be related to zenocutuzumab” being diarrhea (18%), fatigue (12%), and nausea (11%), according to the study authors. Infusion-related reactions were reported in 14% of the patients. One patient discontinued zenocutuzumab due to a treatment-related adverse event.
Based on the results of the phase 2 trial, the investigators concluded that zenocutuzumab “showed efficacy in patients with advanced NRG1 fusion–positive cancer,” including those with NSCLC.
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