The FDA says the approval marks the first systemic therapy for non–small cell lung cancer and pancreatic adenocarcinoma harboring NRG1 gene fusions.

RT’s Three Key Takeaways:

  1. Approved for Advanced NRG1 Fusion-Positive Cancers: The FDA granted accelerated approval for zenocutuzumab-zbco to treat adults with advanced or metastatic non–small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring NRG1 gene fusions.
  2. First FDA-Approved Therapy for NRG1 Gene Fusions: Zenocutuzumab-zbco is the first systemic treatment approved for advanced or metastatic non–small cell lung cancer (NSCLC) and pancreatic adenocarcinoma with NRG1 gene fusions, according to the FDA.
  3. Demonstrated Clinical Efficacy in Trials: The eNRGy trial reported a 33% overall response rate (ORR) for NSCLC and a 40% ORR for pancreatic adenocarcinoma, with median durations of response up to 7.4 months.

The US Food and Drug Administration (FDA) has granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus N.V.) for adults with pancreatic adenocarcinoma or non–small cell lung cancer (NSCLC) that are advanced unresectable or metastatic and harbor a neuregulin 1 (NRG1) gene fusion who have 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, 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 following standard of care treatment. Identification of positive NRG1 gene fusion status was prospectively determined by next-generation sequencing assays.

Efficacy, Safety, and Approval Highlights

The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR), determined by blinded independent central review according to RECIST v1.1. For NSCLC, ORR was 33% (95% CI: 22%, 46%) and median 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.

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 embryo-fetal toxicity.

The recommended zenocutuzumab-zbco dose is 750 mg, as an intravenous infusion every two weeks, until disease progression or unacceptable toxicity.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The application was granted priority review, breakthrough designation, and orphan drug designation. 

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