Bizengri Approved for Lung and Pancreatic Cancers
On Dec. 4, 2024, Merus announced that the U.S. Food and Drug Administration (FDA) granted accelerated approval to Bizengri® (zenocutuzumab-zbco) for adults with pancreatic adenocarcinoma or non-small cell lung cancer (NSCLC) that is advanced, unresectable or metastatic and harbor a neuregulin 1 (NRG1) gene fusion who have disease progression after prior therapy. This is a bispecific antibody that binds to human epidermal growth factor receptors two and three (HER2 and HER3), inhibiting the interaction with NRG1. This is the first therapy specifically for NRG1 gene fusions. The recommended dose of Bizengri is 750mg every two weeks by intravenous (IV) infusion until disease progression or unacceptable toxicity. Premedication prior to each infusion is required to reduce the risk of reactions. Cost information is not yet available. Partner Therapeutics will begin marketing Bizengri in the coming weeks, and full prescribing information can be found here.
At a Glance
- Brand Drug: Bizengri® (zenocutuzumab-zbco)
- Manufacturer: Merus
- Date Approved: Dec. 4, 2024
- Indication: Adults with advanced, unresectable, or metastatic non-small cell lung cancer or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after systemic therapy
- Dosage Forms Available: 375mg/18.75mL (20mg/mL) single-dose vials for dilution and IV infusion
- Launch Date: It is expected to be available in the coming weeks.
- Estimated Annual Cost: Cost is not available at this time.
- NRG1 gene fusions activate cancerous cells and proliferation in a variety of cancer types by activating the avian erythroblastosis B viral oncogene (erbB) receptor family, more specifically, HER2 and HER3 receptors. NRG1 fusions occur in 0.2% of tumors of all tumor types.
- According to the American Cancer Society (ACS), about 66,000 Americans will be diagnosed with pancreatic cancer in 2024 and NRG1 gene fusions occur in about 0.5% of pancreatic cancers each year, which is 330 individuals diagnosed annually. Lung cancer is decreasing annually, but still diagnosed by about 234,000 Americans. NSCLC accounts for up to 85% of all lung cancer cases or 198,900 individuals. NRG1 gene fusions occur in about 0.3% of NSCLC cases or 596 individuals diagnosed annually.
- The accelerated approval is supported by the eNRGy study that evaluated the treatment of NRG1+ solid tumors, including NRG1+ pancreatic adenocarcinoma or NSCLC, in patients who have failed previous therapy or have no alternative treatments. In the arm that evaluated adults with NRG1+ pancreatic adenocarcinoma, 30 patients treated with Bizengri showed a 40% overall response rate (ORR) observed by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The duration of response (DOR) ranged from 3.7 to 16.6 months. In the NSCLC portion of the trial, 65 adults who were NRG1+ were confirmed to have an ORR of 32% by RECIST v1.1 and the DOR was a median of 7.4 months. Continued approval is contingent upon demonstrating a clinical benefit in a confirmatory trial.
- This approval comes with a boxed warning for embryo-fetal toxicity. The most common adverse effects were infusion-related reactions, diarrhea, fatigue, nausea, vomiting, anemia, constipation, stomach pain, difficulty breathing, increased gamma-glutamyl transferase (GGT), and low platelets.
- This is the first approved therapy to target NRG1+ cancers. Targeted therapies in both pancreatic adenocarcinoma and NSCLC have been used; however, they do not provide treatment specifically for NRG1+ tumors.
- Merus is investigating Bizengri in other solid tumors that are NRG1+ and as an adjunct for castration-resistant prostate cancer (CRPC).