Zenocutuzumab-zbco Earns Accelerated Approval for Pancreatic Adenocarcinoma, Non-Small Cell Lung Cancer

Zenocutuzumab-zbco (Bizengri; Merus) has been granted accelerated approval for adults with advanced, unresectable, or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy or advanced, unresectable, or metastatic non–small cell lung cancer (NSCLC) harboring an NRG1 gene fusion with disease progression on or after prior systemic therapy.¹

The approval, announced by FDA officials on December 4, 2024, represents the first FDA approval of a systemic therapy for patients with NSCLC or pancreatic adenocarcinoma harboring an NRG1 gene fusion.

A research team evaluated efficacy in eNRGy (NCT02912949), a multicenter, open-label, multicohort trial that enrolled 64 adults with advanced or metastatic NRG1 fusion–positive NSCLC and 30 adults with advanced or metastatic NRG1 fusion–positive pancreatic adenocarcinoma who had disease progression following standard-of-care treatment. Identification of positive NRG1 gene fusion status was prospectively determined by next-generation sequencing assays.

The researchers noted that for patients with NSCLC, the overall response rate (ORR) was 33% (95% CI, 22%-46%) and median duration of response (DOR) was 7.4 months (95% CI, 4.0-16.6). For pancreatic adenocarcinoma, ORR was 40% (95% CI, 23%-59%) and the DOR range was 3.7 months to 16.6 months.

“The FDA approval of Bizengri marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion. I have seen firsthand how treatment with Bizengri can deliver clinically meaningful outcomes for patients,” Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center and a principal investigator for the ongoing eNRGy trial, said in a press release about the approval.²

Diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema were the most commonly reported adverse events. The most common grade 3 or 4 laboratory abnormalities (≥10%) were increased gamma-glutamyl transferase, decreased hemoglobin, decreased sodium, and decreased platelets. The prescribing information includes a Boxed Warning for embryo-fetal toxicity.

References

1. FDA grants accelerated approval to zenocutuzumab-zbco for non-small cell lung cancer and pancreatic adenocarcinoma. Press release. FDA. Published December 4, 2024. Accessed December 5, 2024. www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zenocutuzumab-zbco-non-small-cell-lung-cancer-and-pancreatic
2. Merus announces FDA approval of Bizengri (zenocutuzumab-zbco) for NRG1+ pancreatic adenocarcinoma and NRG1+ non–small cell lung cancer (NSCLC) based on safety and efficacy data from the eNRGy study. Press release. GlobeNewswire. Published December 4, 2024. Accessed December 5, 2024. www.globenewswire.com/news-release/2024/12/04/2991955/37568/en/Merus-Announces-FDA-Approval-of-BIZENGRI-zenocutuzumab-zbco-for-NRG1-Pancreatic-Adenocarcinoma-and-NRG1-Non-Small-Cell-Lung-Cancer-NSCLC-Based-on-Safety-and-Efficacy-Data-From-the-.html