BIZENGRI® is a bispecific HER2- and HER3-directed antibody that represents a significant advancement in the treatment of specific types of cancer.

Approved under an accelerated approval process, BIZENGRI is indicated for adults with advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion.

This approval is based on the overall response rate and duration of response, with continued approval contingent upon confirmatory trial results.

Afatinib (Gilotrif) for NSCLC

Indications and Usage BIZENGRI is indicated for the treatment of:

1. Non-Small Cell Lung Cancer (NSCLC): For adults with advanced, unresectable, or metastatic NSCLC harboring an NRG1 gene fusion who have experienced disease progression following prior systemic therapy.

2. Pancreatic Adenocarcinoma: For adults with advanced, unresectable, or metastatic pancreatic adenocarcinoma with an NRG1 gene fusion after disease progression on prior systemic therapy.

These indications are approved under the accelerated approval pathway.

Bizengri Dosage and Administration

1. Patient Selection: Treatment with BIZENGRI requires confirmation of the presence of an NRG1 gene fusion.

2. Left Ventricular Ejection Fraction (LVEF) Assessment: Evaluate LVEF prior to initiating therapy.

3. Recommended Dosage: 750 mg every 2 weeks until disease progression or the occurrence of unacceptable toxicity.

4. Premedication: Administer premedications before each infusion to reduce the risk of infusion-related reactions (IRRs).

5. Mode of Administration: BIZENGRI is administered as an intravenous infusion, after dilution, over a period of 4 hours.

Dosage Forms and Strengths:

• BIZENGRI is supplied as a 375 mg/18.75 mL (20 mg/mL) solution in a single-dose vial.

Contraindications to Bizengri:

• There are no known contraindications for BIZENGRI.

Warnings and Precautions:

1. Infusion-Related Reactions (IRRs) / Hypersensitivity / Anaphylaxis:

   • BIZENGRI should be administered in a setting with emergency resuscitation equipment and staff trained to handle infusion-related reactions.

   • Monitor for signs and symptoms of IRR during infusion.

   • For Grade ≤ 3 IRR, interrupt the infusion and administer symptomatic treatment as needed. Resume at a reduced rate after symptoms resolve.

   • For Grade 4 or life-threatening IRR, hypersensitivity, or anaphylaxis, permanently discontinue BIZENGRI.

2. Interstitial Lung Disease (ILD) / Pneumonitis:

   • Monitor patients for new or worsening pulmonary symptoms indicative of ILD or pneumonitis.

   • Permanently discontinue BIZENGRI for Grade ≥2 ILD or pneumonitis.

3. Left Ventricular Dysfunction:

   • Assess LVEF before starting treatment and at regular intervals during treatment.

   • Manage any LVEF dysfunction by interrupting or discontinuing treatment as clinically indicated.

   • Permanently discontinue BIZENGRI in patients with symptomatic congestive heart failure (CHF).

Side Effects of Bizengri:

1. Common Adverse Reactions (≥10% of patients):

   • Diarrhea

   • Musculoskeletal pain

   • Fatigue

   • Nausea

   • Infusion-related reactions (IRR)

   • Dyspnea (shortness of breath)

   • Rash

   • Constipation

   • Vomiting

   • Abdominal pain

   • Edema (swelling)

2. Common Grade 3 or 4 Laboratory Abnormalities (≥2% of patients):

   • Increased gamma-glutamyl transferase (GGT)

   • Decreased hemoglobin

   • Decreased sodium

   • Decreased platelets

   • Increased aspartate aminotransferase (AST)

   • Increased alanine aminotransferase (ALT)

   • Increased alkaline phosphatase

   • Decreased magnesium

   • Decreased phosphate

   • Increased activated partial thromboplastin time (aPTT)

   • Increased bilirubin

Conclusion:

BIZENGRI offers a targeted approach to treating cancers with NRG1 gene fusions, providing a treatment option for patients with limited alternatives.

Its bispecific action against HER2 and HER3 highlights the ongoing evolution of targeted cancer therapies. However, healthcare providers must be vigilant about potential infusion-related reactions, interstitial lung disease, and cardiac dysfunction. Proper monitoring and patient selection are essential for maximizing the benefits of BIZENGRI therapy.