FDA grants accelerated approval to zenocutuzumab-zbco for non-small cell lung cancer and pancreatic adenocarcinoma

Regulatory approval: On Dec 4, 2024, the FDA granted accelerated approval to zenocutuzumab-zbco (Bizengri; Merus N.V.) for adults with advanced, unresectable, or metastatic NRG1 fusion–positive NSCLC or pancreatic adenocarcinoma whose disease progressed on or after prior systemic therapy. Approval was supported by ORR and DOR results from the multicenter, open-label eNRGy trial (NCT02912949). This is described as the first FDA-approved systemic therapy for NRG1 fusion–positive NSCLC or pancreatic adenocarcinoma.

FDA accelerated approval (Dec 4, 2024)

The FDA granted accelerated approval to zenocutuzumab-zbco (Bizengri; Merus N.V.) for adults with:

  • Advanced, unresectable, or metastatic NSCLC with an NRG1 gene fusion and disease progression on or after prior systemic therapy, or
  • Advanced, unresectable, or metastatic pancreatic adenocarcinoma with an NRG1 gene fusion and disease progression on or after prior systemic therapy.

The FDA stated this is the first approval of a systemic therapy for patients with NRG1 fusion–positive NSCLC or pancreatic adenocarcinoma.

Supporting evidence: eNRGy (NCT02912949)

Efficacy was evaluated in eNRGy, a multicenter, open-label, multicohort trial enrolling:

  • 64 adults with advanced/metastatic NRG1 fusion–positive NSCLC, and
  • 30 adults with advanced/metastatic NRG1 fusion–positive pancreatic adenocarcinoma, with progression after standard-of-care treatment. NRG1 fusion status was prospectively identified by next-generation sequencing assays.

Primary efficacy outcomes were confirmed ORR and DOR by blinded independent central review (RECIST v1.1):

  • NSCLC: ORR 33% (95% CI, 22–46); median DOR 7.4 months (95% CI, 4.0–16.6)
  • Pancreatic adenocarcinoma: ORR 40% (95% CI, 23–59); DOR range 3.7–16.6 months

Safety and dosing (label highlights)

Common adverse reactions (≥10%) included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3/4 lab abnormalities (≥10%) included increased GGT, decreased hemoglobin, decreased sodium, and decreased platelets. The prescribing information includes a Boxed Warning for embryo-fetal toxicity.

Recommended dose: 750 mg IV every 2 weeks until disease progression or unacceptable toxicity.

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