BIZENGRI Solution for injection Ref.[113877] Active ingredients: Zenocutuzumab

Source: FDA, National Drug Code (US) Revision Year: 2024

1. Indications and Usage

1.1 Advanced Unresectable or Metastatic NRG1 Fusion-Positive Non-Small Cell Lung Cancer

BIZENGRI is indicated for the treatment of adults with 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.

This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.1)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

1.2 Advanced Unresectable or Metastatic NRG1 Fusion-Positive Pancreatic Adenocarcinoma

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

2. Dosage and Administration

2.1 Patient Selection

Select patients for treatment with BIZENGRI based on the presence of an NRG1 gene fusion in tumor specimens [see Clinical Studies (14.1, 14.2)].

An FDA-approved test for the detection of NRG1 gene fusions is not currently available.

2.2 Recommended Evaluation Before Initiating BIZENGRI

Before initiating BIZENGRI, evaluate left ventricular ejection fraction (LVEF) [see Warnings and Precautions (5.3)].

2.3 Recommended Dosage

The recommended dosage of BIZENGRI is 750 mg as an intravenous (IV) infusion every 2 weeks until disease progression or unacceptable toxicity [see Dosage and Administration (2.7)].
Administer premedications before each BIZENGRI infusion as recommended to reduce the risk of infusion-related reactions [see Dosage and Administration (2.4)].

2.4 Recommended Premedications

Prior to each infusion of BIZENGRI, administer premedications to reduce the risk of infusion-related reactions (IRRs) [see Warnings and Precautions (5.1)] (see Table 1).

Table 1. Premedications Prior to BIZENGRI Infusions:

Medication	Dose	Route of Administration
Corticosteroid¹	Dexamethasone (10 mg)	Oral or intravenous
Antipyretic	Acetaminophen (1,000 mg)	Oral or intravenous
H1 Antihistamine	Dexchlorpheniramine (5 mg) or other anti-H1 equivalent	Intravenous or oral

¹ Optional after initial BIZENGRI infusion

2.5 Dosage Modifications for Adverse Reactions

No dose reduction is recommended for BIZENGRI. The recommended dosage modifications of BIZENGRI for adverse reactions are provided in Table 2.

Table 2. Recommended BIZENGRI Dosage Modifications and Management for Adverse Reactions:

Adverse Reaction	Severity Dose	Modifications and Management
Infusion-related reactions (IRRs)/Hypersensitivity/ Anaphylactic Reactions [see Warnings and Precautions (5.1)]	≤ Grade 3 IRR	• Interrupt BIZENGRI infusion if IRR is suspected and monitor patient until reaction symptoms resolve. • Provide symptomatic treatment as needed. • Resume the infusion at 50% of the infusion rate at which the reaction occurred. The infusion rate may be escalated if there are no additional symptoms. • Corticosteroid premedication can be used as necessary for subsequent BIZENGRI infusions [see Recommended Premedications (2.4)].
	Grade 4 IRR or any grade hypersensitivity/ anaphylactic reaction	• Permanently discontinue BIZENGRI.
Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.2)]	Grade 1	• Interrupt BIZENGRI until recovery. • Consider prompt initiation of corticosteroids when the diagnosis is suspected. • Resume treatment after resolution.
	≥ Grade 2	• Permanently discontinue BIZENGRI. • Promptly treat with corticosteroids.
Left Ventricular Dysfunction [see Warnings and Precautions (5.3)]	LVEF is 45-49% and absolute decrease from baseline ≥10% or LVEF less than 45%	• Interrupt BIZENGRI. • Repeat LVEF assessment within 3 weeks. • If LVEF is less than 45% or LVEF has not recovered to within 10% from baseline, permanently discontinue BIZENGRI. • If LVEF is 50% or greater or LVEF is 45-49% and recovered to within 10% of baseline, resume BIZENGRI and monitor LVEF every 12 weeks while on treatment and as clinically indicated.
	Symptomatic congestive heart failure (CHF)	• Permanently discontinue BIZENGRI.
Other Clinically Relevant Adverse Reactions [see Adverse Reactions (6.1)]	Grade 3 or 4	• Withhold BIZENGRI until recovery to ≤ Grade 1 or baseline. • Provide symptomatic treatment as needed. • Resume treatment after resolution of symptoms.

2.6 Preparation

Dilute and prepare BIZENGRI for intravenous infusion before administration.

For the initial infusion, prepare BIZENGRI as close to administration time as possible to allow for the possibility of extended infusion time in the event of an infusion-related reaction.

Check that the BIZENGRI solution is clear to slightly opalescent, colorless to slightly yellow. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if discoloration or visible particles are present.
Withdraw and then discard 37.5 mL 0.9% Sodium Chloride Injection from the 250 mL infusion bag. Only use infusion bags made of polyvinylchloride (PVC), polyolefin or polyolefin/polyamide coextruded plastic.
Withdraw a total of 37.5 mL of BIZENGRI from 2 vials and add it to the infusion bag. The final volume in the infusion bag should be 250 mL. Discard any unused portion left in the vial.
Gently invert the bag to mix the solution. Do not shake.
If not used immediately, store the diluted solution refrigerated at 2°C to 8°C (36°F to 46°F) and protect from light after preparation unless the infusion is initiated within 2 hours of preparation.

2.7 Administration

If the infusion time exceeds the recommended storage time, the infusion bag must be discarded and a new infusion bag prepared to continue the infusion. Diluted BIZENGRI solution must by administered within:
- 6 hours from end of preparation of infusion solution stored at room temperature [15°C to 25°C (59°F to 77°F)]
- 28 hours from end of preparation of infusion solution stored refrigerated [2°C to 8°C (36°F to 46°F)]
If the diluted BIZENGRI solution has been refrigerated, allow it to reach room temperature (approximately 30 minutes) prior to administration.
Administer diluted BIZENGRI solution [see Dosage and Administration (2.6)] by intravenous infusion using an infusion set made of either PVC, polyethylene (PE), polyurethane (PUR) or polybutadiene (PB) with an in-line, sterile, non-pyrogenic, low protein-binding polyethersulfone (PES) filter (pore size 0.2 micrometer).
Do not infuse BIZENGRI concomitantly in the same IV line with other agents.
Administer BIZENGRI infusion via a peripheral or central line.
Monitor patients closely for signs and symptoms of infusion-related reactions during BIZENGRI infusion and monitor patients for at least 1 hour following completion of the first BIZENGRI infusion and as clinically indicated [see Warnings and Precautions (5.1)].
Administer intravenous infusion over 4 hours.

16.2. Storage and Handling

Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze. Do not shake.

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