The U.S. Food and Drug Administration (FDA) approved accelerated approval of Zenocutuzumab-zbco (sold under the brand name Bizengri by Merus N.V.) for the treatment of advanced non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring NRG1 gene fusions. This is the first FDA-approved systemic therapy that targets these rare genetic mutations.Key Points from the Approval:
Indications:

• Non-Small Cell Lung Cancer (NSCLC): Adults with advanced, unresectable, or metastatic NSCLC and whose disease has progressed after prior systemic therapy.

• Pancreatic Adenocarcinoma: Adults with advanced, unresectable, or metastatic pancreatic adenocarcinoma and whose disease has progressed after prior systemic therapy.

Clinical Trial Results:

• The eNRGy Study (NCT02912949) was a multicenter, open-label study that included 94 patients with NRG1 fusion-positive cancers (64 with NSCLC and 30 with pancreatic adenocarcinoma).

• Efficacy Results:

• NSCLC: ORR = 33%, and median duration of response = 7.4 months.

• Pancreatic Adenocarcinoma: ORR = 40%, and DOR range, 3.7 to 16.6 months.

Safety Profile:
Most common adverse reactions (≥10%): Diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, rash, and abdominal pain.
Common Grade 3 or 4 laboratory abnormalities (≥10%): Increased gamma-glutamyl transferase, decreased hemoglobin, sodium, and platelets.
Includes a Boxed Warning for embryo-fetal toxicity, underscoring the need for caution during pregnancy.Recommended Dose:
750 mg intravenous infusion given every 2 weeks, discontinued due to disease progression or unacceptable toxicity.Title: FDA Grants Accelerated Approval to Zenocutuzumab-zbco for Advanced Lung and Pancreatic Cancers
Date: December 6, 2024
Content:
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Zenocutuzumab-zbco (marketed as Bizengri by Merus N.V.) for the treatment of advanced non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring NRG1 gene fusions. This marks the first FDA-approved systemic therapy targeting these rare genetic mutations.
Key Highlights of the Approval:

1. Indications:

   • Non-Small Cell Lung Cancer (NSCLC): For adults with advanced, unresectable, or metastatic NSCLC with disease progression after prior systemic therapy.

   • Pancreatic Adenocarcinoma: For adults with advanced, unresectable, or metastatic pancreatic adenocarcinoma with disease progression after prior systemic therapy.

2. Clinical Trial Results:

3. The eNRGy Study (NCT02912949), a multicenter, open-label trial, evaluated 94 patients with NRG1 fusion-positive cancers (64 with NSCLC and 30 with pancreatic adenocarcinoma).

4. Efficacy Outcomes:

   • NSCLC: Overall response rate (ORR) of 33% and median duration of response (DOR) of 7.4 months.

   • Pancreatic Adenocarcinoma: ORR of 40% with a DOR range of 3.7 to 16.6 months.

5. Safety Profile:

6. Most common adverse reactions (≥10%): Diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, rash, and abdominal pain.

7. Common Grade 3 or 4 laboratory abnormalities (≥10%): Increased gamma-glutamyl transferase, decreased hemoglobin, sodium, and platelets.

8. Includes a Boxed Warning for embryo-fetal toxicity, underscoring the need for caution during pregnancy.

4. Recommended Dose:
750 mg as an intravenous infusion every 2 weeks, continued until disease progression or unacceptable toxicity.5. Expedited Programs:
The drug has been approved through FDA expedited programs, such as priority review, breakthrough therapy designation, and orphan drug designation. The review used the Assessment Aid from the FDA, which helps the agency expedite reviews of serious drugs.

Action Needed by Healthcare Professionals:
Healthcare professionals are advised to closely monitor patients for adverse reactions and to report any serious adverse events to the FDA MedWatch Reporting System at 1-800-FDA-1088.
This achievement underscores the significance of next-generation sequencing in the identification of genetic mutations such as NRG1 fusions and the provision of targeted therapies to patients with few other choices.