On 4 December 2024, the US Food and Drug Administration (FDA) granted accelerated approval to zenocutuzumab-zbco (Bizengri, Merus N.V.) for adults with:
- advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) harbouring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy, or
- advanced, unresectable, or metastatic pancreatic adenocarcinoma harbouring a 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 harbouring an NRG1 gene fusion.
Efficacy was evaluated in the eNRGy study (NCT02912949), a multicentre, open-label, multicohort study. 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.
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% confidence interval [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 diarrhoea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnoea, rash, constipation, vomiting, abdominal pain, and oedema. The most common Grade 3 or 4 laboratory abnormalities (≥10%) were increased gamma-glutamyl transferase, decreased haemoglobin, decreased sodium, and decreased platelets. The prescribing information includes a Boxed Warning for embryo-foetal toxicity.
The recommended zenocutuzumab-zbco dose is 750 mg, as an intravenous infusion every 2 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.
This application was granted priority review, breakthrough designation, and orphan drug designation.
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