FDA approves zenocutuzumab-zbco for lung and pancreatic cancer

On December 4, 2024, the Food and Drug Administration (FDA) granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus N.V.) for adult patients suffering from advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) as well as for those with metastatic pancreatic adenocarcinoma. This approval targets patients whose cancers harbor a neuregulin 1 (NRG1) gene fusion and have shown disease progression following prior systemic therapy. This marks the inaugural FDA approval of a systemic therapy specifically for patients with NSCLC or pancreatic adenocarcinoma containing an NRG1 gene fusion.

The efficacy of Bizengri was assessed through the eNRGy study (NCT02912949), which was a multicenter, open-label, multicohort trial. This trial incorporated 64 adults with advanced or metastatic NRG1 fusion-positive NSCLC and 30 adults with advanced or metastatic NRG1 fusion-positive pancreatic adenocarcinoma, all of whom had experienced disease progression after standard treatments. Identification of positive NRG1 gene fusion status was prospectively determined using next generation sequencing assays.

The major efficacy outcomes evaluated were the confirmed overall response rate (ORR) and duration of response (DOR), determined by an independent central review according to RECIST v1.1 criteria. In the NSCLC cohort, the ORR was 33% (95% CI: 22%, 46%) with a median DOR of 7.4 months (95% CI: 4.0, 16.6). For the pancreatic adenocarcinoma cohort, the ORR was 40% (95% CI: 23%, 59%) and the DOR ranged from 3.7 months to 16.6 months.

In terms of safety, the most common adverse reactions observed in the pooled safety population (occurring in ≥10% of patients) included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. The most frequent Grade 3 or 4 laboratory abnormalities (≥10%) were increased gamma-glutamyl transferase, decreased hemoglobin, decreased sodium, and decreased platelets. The prescribing information for Bizengri carries a Boxed Warning for embryo-fetal toxicity.

The recommended dosage of zenocutuzumab-zbco is 750 mg, administered as an intravenous infusion every two weeks until disease progression or the patient experiences unacceptable toxicity.

This application benefited from several of the FDA's expedited programs. It received priority review, breakthrough therapy designation, and orphan drug designation. These programs are outlined in the FDA’s Guidance for Industry on Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals are encouraged to report any serious adverse events suspected to be associated with the use of Bizengri to the FDA’s MedWatch Reporting System. For assistance with single-patient INDs for investigational oncology products, healthcare professionals can contact the Oncology Center of Excellence’s Project Facilitate.