On December 4, 2024, Merus N.V. announced the FDA approved BIZENGRI® (zenocutuzumab-zbco) as a treatment indicated for adults with pancreatic adenocarcinoma or NSCLC that are advanced unresectable or metastatic and harbor a NRG1 gene fusion who have disease progression on or after prior systemic therapy.
Zenocutuzumab is a humanized, ADCC-enhanced, bispecific IgG1k antibody that simultaneously targets the growth factor receptors HER2 and HER3, thereby blocking signal transduction caused by the binding of HER3 with its ligand neuregulin 1 (NRG1) or NRG1-fusion proteins. The antibody is in development by Merus as a treatment for patients with solid tumors harboring NRG1 gene fusions (NRG1+ cancer), who typically have suboptimal responses to conventional systemic treatment. FDA granted Breakthrough Therapy Designation for zenocutuzumab for the treatment of patients with advanced unresectable or metastatic NRG1+ pancreatic cancer following progression with prior systemic therapy or who have no satisfactory alternative treatment options, as well as Fast Track Designation for the treatment of patients with metastatic NRG1+ cancer that have progressed on standard of care therapy and Orphan Drug Designation for the treatment of patients with pancreatic cancer.
FDA’s approval was based on data from the open-label Phase 1/2 eNRGy trial (NCT02912949), which evaluated the safety and anti-tumor activity of zenocutuzumab monotherapy in NRG1+ NSCLC, PDAC, and other solid tumors. The study consisted of three patient cohorts: 1) NRG1+ NSCLC, 2) NRG1+ PDAC, and 3) other NRG1+ solid tumors. In the dose expansion period of the eNRGy study, participants received IV infusions of 750 mg of zenocutuzumab Q2W. Response rates were measured using RECIST v1.1 as assessed by blinded ICR. The ORR was 33% (95% CI, 22%-46%) and 40% (95% CI, 23%-59%) in the NRG1+ NSCLC (n=64) and NRG1+ PDAC (n=30) cohorts, respectively, and the median DOR was 7.4 months (95% CI, 4.0-16.6) in the NRG1+ NSCLC cohort and ranged from 3.7 months to 16.6 months in the NRG1+ PDAC cohorts.
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