FDA Approves Bizengri (zenocutuzumab-zbco) for NRG1+ Pancreatic and Non-Small Cell Lung Cancers
核心洞察
The FDA has granted accelerated approval to Bizengri (zenocutuzumab-zbco) for advanced unresectable or metastatic NRG1 (搜索)+ pancreatic adenocarcinoma (搜索) and non-small cell lung cancer (搜索) (NSCLC).
Bizengri is the first and only FDA-approved therapy specifically targeting NRG1 (搜索) gene fusions in these cancers, offering a new treatment option for patients with disease progression after prior systemic therapy.
Approval was based on overall response rate (ORR) and duration of response (DOR) data from the eNRGy trial, with continued approval contingent on confirmatory trial results.
The U.S. Food and Drug Administration (FDA) has approved Bizengri (zenocutuzumab-zbco) for the treatment of adult patients with advanced unresectable or metastatic pancreatic adenocarcinoma (搜索) or non-small cell lung cancer (搜索) (NSCLC) harboring a neuregulin 1 (NRG1 (搜索)) gene fusion. This approval marks a significant advancement as Bizengri is the first and only therapy specifically indicated for these cancers with NRG1 gene fusions who have disease progression on or after prior systemic therapy.
The approval is based on data from the eNRGy trial, a multicenter, open-label clinical trial (NCT02912949) that evaluated the safety and efficacy of Bizengri in patients with NRG1 (搜索)+ pancreatic adenocarcinoma (搜索) or NRG1+ NSCLC. The indications are approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Efficacy Data from the eNRGy Trial
In the NRG1 (搜索)+ pancreatic adenocarcinoma (搜索) cohort (n=30), Bizengri demonstrated an ORR of 40% (95% CI, 23%-59%). The duration of response (DOR) ranged from 3.7 months to 16.6 months. For patients with NRG1+ NSCLC (n=64), the ORR was 33% (95% CI, 22%-46%), with a median DOR of 7.4 months (95% CI, 4.0-16.6). Response rates were assessed using RECIST v1.1 by blinded independent central review (BICR).
Safety Profile
The most common adverse reactions (≥10%) observed in the pooled safety population (N=175) were diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions (IRR), dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities (≥2%) included increased gamma-glutamyltransferase, decreased hemoglobin, decreased sodium, decreased platelets, increased aspartate aminotransferase, increased alanine aminotransferase, increased alkaline phosphatase, decreased magnesium, decreased phosphate, increased activated partial thromboplastin time, and increased bilirubin.
Bizengri carries a Boxed WARNING for Embryo-Fetal Toxicity and warnings for infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions, interstitial lung disease (ILD)/pneumonitis, and left ventricular dysfunction.
Mechanism of Action
Bizengri is a bispecific antibody that binds to the extracellular domains of HER2 (搜索) and HER3 (搜索), inhibiting HER2:HER3 dimerization and preventing NRG1 (搜索) binding to HER3. This action decreases cell proliferation and signaling through the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway. Bizengri also mediates antibody-dependent cellular cytotoxicity and has shown antitumor activity in mouse models of NRG1+ lung and pancreatic cancers.
Clinical Significance
"The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma (搜索) or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 (搜索) gene fusion. I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients," said 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.
This approval addresses a critical unmet need for patients with NRG1 (搜索)+ cancers, offering a targeted therapy where limited options previously existed. Merus and Partner Therapeutics announced a license agreement for U.S. commercialization. BIZENGRI® (zenocutuzumab-zbco) 20 mg/mL Injection for Intravenous Use is expected to be available to patients in the coming weeks.