OPDUALAG Concentrate for solution for infusion Ref.[50204] Active ingredients: Nivolumab

Treatment must be initiated and supervised by physicians experienced in the treatment of cancer.

Patients treated with Opdualag must be given the patient card and be informed about the risks of Opdualag (see also package leaflet).

PD-L1 testing

Patients should be selected for treatment with Opdualag based on the tumour expression of PD-L1 confirmed by a validated test (see sections 4.4 and 5.1).

Posology

The recommended dose for adults and adolescents 12 years of age and older is 480 mg nivolumab and 160 mg relatlimab every 4 weeks administered as an intravenous infusion over 30 minutes. This dose is established for adolescent patients weighing at least 30 kg (see section 5.2).

Treatment with Opdualag should be continued as long as clinical benefit is observed or until treatment is no longer tolerated by the patient. Dose escalation or reduction is not recommended. Dosing delay or discontinuation may be required based on individual safety and tolerability. Guidelines for permanent discontinuation or withholding of doses are described in Table 1. Detailed guidelines for the management of immune-related adverse reactions are described in section 4.4.

Table 1. Recommended treatment modifications for Opdualag:

Note: Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5).
^a Recommendation for the use of hormone replacement therapy is provided in section 4.4.
^b The safety of re-initiating Opdualag in patients previously experiencing immune-related myocarditis is not known.

Special populations

Paediatric population

The safety and efficacy of Opdualag in children below 12 years of age have not been established. No data are available (see section 5.2).

Elderly

No dose adjustment is required for elderly patients (≥65 years) (see section 5.2).

Renal impairment

No dose adjustment is required in patients with mild or moderate renal impairment (see section 5.2). Data from patients with severe renal impairment are too limited to draw conclusions on this population.

Hepatic impairment

No dose adjustment is required in patients with mild or moderate hepatic impairment (see section 5.2). Data from patients with severe hepatic impairment are too limited to draw conclusions on this population.

Method of administration

Opdualag is for intravenous use only. It is to be administered as an intravenous infusion over a period of 30 minutes.

Opdualag must not be administered as an intravenous push or bolus injection. Opdualag can be used without dilution, or may be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection or glucose 50 mg/mL (5%) solution for injection (see section 6.6).

For instructions on the preparation and handling of the medicinal product before administration, see section 6.6.

In case of overdose, patients should be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted immediately.

Unopened vial:

3 years.

After preparation of infusion:

Chemical and physical in-use stability from the time of preparation has been demonstrated as follows (times are inclusive of the administration period):

From a microbiological point of view, the prepared solution for infusion, regardless of the diluent, should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless preparation has taken place in controlled and validated aseptic conditions (see section 6.6).

Store in a refrigerator (2°C-8°C).

Do not freeze.

Keep the vial in the outer carton in order to protect from light.

The unopened vials can be stored at controlled room temperature (up to 25°C) for up to 72 hours.

For storage conditions after preparation of the infusion, see section 6.3.

Pack of one 25 mL vial (Type I glass), with a stopper (coated butyl rubber) and a yellow flip-off aluminium seal. Each vial is filled with 21.3 mL of solution, which includes an overfill of 1.3 mL.

Opdualag is supplied as a single-dose vial and does not contain any preservatives. Preparation should be performed by trained personnel in accordance with good practices rules, especially with respect to asepsis.

Opdualag can be used for intravenous administration either:

• without dilution, after transfer to an infusion container using an appropriate sterile syringe; or
• after diluting according to the following instructions:
• the final infusion concentration should range between 3 mg/mL of nivolumab and 1 mg/mL of relatlimab to 12 mg/mL of nivolumab and 4 mg/mL of relatlimab
• the total volume of infusion must not exceed 160 mL. For patients weighing less than 40 kg, the total volume of infusion should not exceed 4 mL per kilogram of patient weight.

Opdualag concentrate may be diluted with either:

• sodium chloride 9 mg/mL (0.9%) solution for injection; or
• 50 mg/mL (5%) glucose solution for injection.

Preparing the infusion:

• Inspect the Opdualag concentrate for particulate matter or discolouration. Do not shake the vial. Opdualag is a clear to opalescent, colourless to slightly yellow solution. Discard the vial if the solution is cloudy, discoloured, or contains extraneous particulate matter.
• Withdraw the required volume of Opdualag concentrate using an appropriate sterile syringe and transfer the concentrate into a sterile, intravenous container (ethylvinyl acetate (EVA), polyvinyl chloride [PVC], or polyolefin).
• If applicable, dilute Opdualag solution with the required volume of sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) glucose solution for injection. For ease of preparation, the concentrate can also be transferred directly into a pre-filled bag containing the appropriate volume of sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) glucose solution for injection.
• Gently mix the infusion by manual rotation. Do not shake.

Administration:

Opdualag infusion must not be administered as an intravenous push or bolus injection.

Administer the Opdualag infusion intravenously over a period of 30 minutes. Use of an infusion set and an in-line or add-on, sterile, non-pyrogenic, low protein binding filter (pore size of 0.2 μm to 1.2 μm) is recommended.

Opdualag infusion is compatible with EVA, PVC and polyolefin containers, PVC infusion sets and in-line filters with polyethersulfone (PES), nylon, and polyvinylidene fluoride (PVDF) membranes with pore sizes of 0.2 μm to 1.2 μm. Do not co-administer other medicinal products through the same infusion line. After administration of the Opdualag dose, flush the line with sodium chloride 9 mg/mL (0.9%) solution for injection or 50 mg/mL (5%) glucose solution for injection.

Disposal:

Do not store any unused portion of the infusion solution for reuse. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.