On December 4, 2024, the U.S. Food and Drug Administration granted accelerated approval to the HER2 × HER3 bispecific antibody zenocutuzumab-zbco (Bizengri) for adults with the following types of lung and pancreatic cancers:
- advanced, unresectable, or metastatic non–small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy, or
- advanced, unresectable, or metastatic pancreatic adenocarcinoma harboring an NRG1 gene fusion with disease progression on or after prior systemic therapy.
This represents the first FDA approval of a systemic therapy for patients with NSCLC or pancreatic adenocarcinoma harboring an NRG1 gene fusion.
Efficacy was evaluated in the eNRGy study (ClinicalTrials.gov identifier NCT02912949), a multicenter, open-label, multicohort trial. The trial 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 after standard-of-care treatment. Identification of positive NRG1 gene fusion status was prospectively determined by next-generation sequencing assays.
The major efficacy outcome measures were confirmed overall response rate and duration of response, determined by blinded independent central review according to Response Evaluation Criteria in. Solid Tumors v1.1. For NSCLC, the overall response rate was 33% (95% confidence interval [CI] = 22%–46%), and the median duration of response was 7.4 months (95% CI = 4.0–16.6 months). For pancreatic adenocarcinoma, the overall response rate was 40% (95% CI = 23%–59%), and the duration of response range was 3.7 months to 16.6 months.
In the pooled safety population, the most common adverse reactions (≥ 10%) were diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. 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 embryofetal toxicity.
The recommended dose of zenocutuzumab-zbco is 750 mg, as an intravenous infusion every 2 weeks, until disease progression or unacceptable toxicity.
