FDA approves first therapy for lung, pancreatic cancers harboring NRG1 gene fusion

December 6, 2024

Brand name: Bizengri

Generic name: zenocutuzumab-zbco

Manufacturer: Merus N.V.

Approval date: December 4, 2024

FDA granted accelerated approval to Bizengri (zenocutuzumab-zbco), a bispecific HER2- and HER3-directed antibody, for adults with the following indications:

• 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
• 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.

According to a manufacturer press release, the indications are approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval may be contingent upon verification in a confirmatory trial(s).

Efficacy

Efficacy was evaluated in the eNRGy study (NCT02912949), a multicenter, open-label, multicohort trial that 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 ORR and DOR. 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.

Safety

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 lab abnormalities (≥2%) were increased GGT, decreased Hgb, decreased sodium, and decreased platelets. The prescribing information includes a Boxed Warning for embryo-fetal toxicity.

Recommended dose

The recommended dose of zenocutuzumab-zbco is 750 mg, as an IV infusion q2wks, until disease progression or unacceptable toxicity.

Sources:

FDA. (2024, December 4). FDA grants accelerated approval to zenocutuzumab-zbco for non-small cell lung cancer and pancreatic adenocarcinoma. [Press release]. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zenocutuzumab-zbco-non-small-cell-lung-cancer-and-pancreatic

Merus N.V. (2024, December 4). Merus Announces FDA Approval of BIZENGRI® (zenocutuzumab-zbco) for NRG1+ Pancreatic Adenocarcinoma and NRG1+ Non–Small Cell Lung Cancer (NSCLC) Based on Safety and Efficacy Data From the eNRGy Study. [News release]. https://ir.merus.nl/news-releases/news-release-details/merus-announces-fda-approval-bizengrir-zenocutuzumab-zbco-nrg1

Merus N.V.: Bizengri (zenocutuzumab-zbco) [Package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761352s001lbl.pdf