New England Journal of Medicine Publishes: Efficacy of Zenocutuzumab in NRG1 Fusion-Positive Cancer

Core Insights - Merus N.V. announced the publication of results from the eNRGy trial for Bizengri (zenocutuzumab), the first treatment for adults with advanced unresectable or metastatic pancreatic adenocarcinoma or non-small cell lung cancer (NSCLC) harboring NRG1 gene fusion [1][2][3] Company Overview - Merus is a clinical-stage oncology company focused on developing innovative full-length multispecific antibodies, known as Biclonics and Triclonics [1][29] - The company has made significant progress in its clinical pipeline, emphasizing the importance of its proprietary Biclonics antibody technologies [2] Clinical Trial Results - The eNRGy trial included 204 patients across 12 tumor types, demonstrating durable efficacy of Bizengri in advanced NRG1+ cancers, particularly in NSCLC and pancreatic adenocarcinoma, with a favorable safety profile [3][21] - The trial's main outcome measures were overall response rate (ORR) and duration of response (DOR), assessed by independent central review [21] Treatment Indications - Bizengri is indicated for adults with advanced unresectable or metastatic pancreatic adenocarcinoma or NSCLC with NRG1 gene fusion who have disease progression after prior systemic therapy [5][20] - The treatment received accelerated approval based on ORR and DOR, with continued approval contingent upon further verification of clinical benefit [5] Licensing Agreement - In December, Merus entered into an exclusive licensing agreement with Partner Therapeutics, Inc. for the commercialization of zenocutuzumab in the U.S. [4] Safety and Efficacy - The publication highlights the safety and efficacy of Bizengri, with serious adverse reactions reported in 23% of patients with NRG1+ pancreatic adenocarcinoma and 25% in NRG1+ NSCLC [15][17] - Common adverse reactions included increased alanine aminotransferase (51%), diarrhea (36%), and fatigue (21%) among pancreatic adenocarcinoma patients [16] Mechanism of Action - Bizengri is a bispecific antibody that inhibits HER2:HER3 dimerization and prevents NRG1 binding to HER3, leading to decreased cell proliferation and signaling through the PI3K-AKT-mTOR pathway [20] Patient Demographics - In the NRG1+ pancreatic adenocarcinoma group, the median age was 49 years, with 43% female and 87% White [22] - In the NRG1+ NSCLC group, the median age was 64 years, with 64% female and 56% Asian [23]