On December 4, 2024, the FDA granted accelerated approval to zenocutuzumab-zbco (Bizengri), marking a significant milestone in cancer care. This is the first approved systemic therapy targeting NRG1 gene fusions, a rare but actionable driver mutation in certain cancers. Zenocutuzumab-zbco is approved for adults with:
- Advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) harboring an NRG1 fusion, with disease progression following systemic therapy.
- Advanced, unresectable, or metastatic pancreatic adenocarcinoma harboring an NRG1 fusion, with disease progression following systemic therapy.
This approval offers a new, precision-medicine option for patients with these challenging cancers.
Understanding NRG1 Gene Fusions
NRG1 (neuregulin 1) gene fusions are rare genetic alterations that drive tumor growth by activating the HER3 signaling pathway. These fusions are found in approximately:
- 0.2%-0.5% of NSCLC cases,
- 0.5%-1% of pancreatic adenocarcinomas,
making them critical but difficult targets in oncology.
NRG1 fusion-positive cancers often resist standard treatments, which underscores the importance of targeted therapies like zenocutuzumab-zbco.
Clinical Trial Data: The eNRGy Study
The FDA approval was based on results from the eNRGy trial, a multicenter, open-label study evaluating zenocutuzumab-zbco in adults with advanced or metastatic NRG1 fusion-positive cancers.
Key Results:
- For NSCLC:
- Overall Response Rate (ORR): 33% (95% CI: 22%, 46%).
- Median Duration of Response (DOR): 7.4 months (95% CI: 4.0, 16.6).
- For Pancreatic Adenocarcinoma:
- ORR: 40% (95% CI: 23%, 59%).
- DOR Range: 3.7 to 16.6 months.
These results highlight zenocutuzumab-zbco’s ability to deliver meaningful responses, even in heavily pretreated patients.
Safety Profile and Administration
Zenocutuzumab-zbco demonstrated a manageable safety profile, consistent with targeted therapies.
Most Common Adverse Reactions (≥10%):
- Diarrhea, musculoskeletal pain, fatigue, nausea, and infusion-related reactions.
- Other common reactions included dyspnea, rash, abdominal pain, vomiting, and edema.
Common Grade 3 or 4 Laboratory Abnormalities (≥10%):
- Increased gamma-glutamyl transferase, decreased hemoglobin, decreased sodium, and decreased platelets.
Boxed Warning: The prescribing information includes a warning for embryo-fetal toxicity, emphasizing the importance of pregnancy prevention during treatment.
Recommended Dose: 750 mg, administered intravenously every two weeks, until disease progression or unacceptable toxicity.
Implications for Oncology Care
The approval of zenocutuzumab-zbco is a milestone in precision medicine and cancer care, offering new hope to patients with limited treatment options. Here’s why it matters:
- First Therapy for NRG1 Fusions: This approval establishes a targeted option for a rare but clinically significant mutation, paving the way for further innovations in precision oncology.
- Expanding Options for NSCLC and Pancreatic Cancer: These cancers are notoriously difficult to treat in advanced stages. This therapy provides a targeted approach for patients with limited systemic options.
- Encouraging Responses: While the response rates and durations vary, the results demonstrate the potential of targeting NRG1 fusions with significant and durable outcomes for some patients.
For Providers and Patients
Next Steps for Providers:
- Ensure patients undergo next-generation sequencing (NGS) to identify NRG1 gene fusions. Accurate molecular testing is essential for selecting candidates for zenocutuzumab-zbco.
- Familiarize yourself with the administration schedule and potential side effects to counsel patients effectively.
What Patients Should Know:
- This therapy is a targeted option specifically for cancers with NRG1 fusions, determined by specialized genetic testing.
- Side effects are manageable but may include fatigue, gastrointestinal symptoms, and infusion-related reactions. Speak to your oncologist about how to address these.
- Ask about eligibility for this treatment and discuss how it fits into your overall care plan.
Looking Ahead
The approval of zenocutuzumab-zbco is a testament to the power of precision oncology and targeted therapy development. While it represents a breakthrough for patients with NRG1 fusions, further research is needed to expand its applications and explore combination therapies that might improve outcomes further.
For now, this approval gives hope to a group of patients with challenging cancers, reinforcing the critical role of molecular testing in guiding personalized treatment strategies.
For more updates on groundbreaking cancer therapies, stay tuned to MedOncMD.com.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology.