TEVIMBRA Concentrate for solution for infusion Ref.[51271] Active ingredients: Tislelizumab

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

PD-L1 testing

If specified in the indication, patient selection for treatment with Tevimbra based on the tumour expression of PD-L1 should be assessed by a CE-marked IVD with the corresponding intended purpose. If the CE-marked IVD is not available, an alternative validated test should be used (see sections 4.1, 4.4, and 5.1).

Posology

Tevimbra monotherapy

The recommended dose of Tevimbra is 200 mg administered by intravenous infusion once every 3 weeks.

Tevimbra combination therapy

The recommended dose of Tevimbra is 200 mg administered by intravenous infusion once every 3 weeks, in combination with chemotherapy.

When Tevimbra and chemotherapy are administered on the same day, Tevimbra should be administered before chemotherapy. The Summary of Product Characteristics (SmPC) for the chemotherapy product should be referred to for dosing as well as for recommendations on corticosteroid use as pre-medication for the prevention of chemotherapy-related adverse reactions.

Duration of treatment

Patients should be treated with Tevimbra until disease progression or unacceptable toxicity (see section 5.1).

Dose delay or discontinuation (see also section 4.4)

Dose reductions of Tevimbra as monotherapy or in combination therapy are not recommended. Tevimbra should be withheld or discontinued based on safety and tolerability as 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 Tevimbra:

ALT = alanine aminotransferase, AST = aspartate aminotransferase, HRT = hormone replacement therapy, SJS = Stevens-Johnson syndrome, TEN = Toxic epidermal necrolysis, ULN = upper limit of normal
¹ Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0). Hypophysitis grade is in accordance with NCI-CTCAE v5.0.
² Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper over at least 1 month. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating corticosteroids or inability to reduce prednisone to ≤10 mg/day (or equivalent) within 12 weeks of initiating corticosteroids.
³ Initial dose of 1 to 2 mg/kg/day prednisone or equivalent followed by a taper to ≤10 mg/day (or equivalent) over at least 1 month is recommended, except for pneumonitis, where initial dose of 2 to 4 mg/kg/day is recommended.

Special populations

Paediatric population

The safety and efficacy of Tevimbra in patients aged below 18 years have not been established. No data are available.

Elderly

No dose adjustment is needed for patients aged ≥65 years (see section 4.8).

Renal impairment

No dose adjustment is needed for patients with mild or moderate renal impairment. Data from patients with severe renal impairment are too limited to make dosing recommendations for this population (see section 5.2).

Hepatic impairment

No dose adjustment is needed for patients with mild or moderate hepatic impairment. Data from patients with severe hepatic impairment are too limited to make dosing recommendations for this population (see section 5.2).

Method of administration

Tevimbra is for intravenous use only. It is to be administered as an infusion and must not be administered as an intravenous push or single bolus injection. For instructions on dilution of the medicinal product before administration, see section 6.6.

The first infusion should be administered over a period of 60 minutes. If this is well tolerated, the subsequent infusions may be administered over a period of 30 minutes. The infusion should be given via an intravenous line containing a sterile, non-pyrogenic, low-protein-binding 0.2 or 0.22 micron in-line or add-on filter.

Other medicinal products must not be mixed or co-administered through the same infusion line.

There is no information on overdose with tislelizumab. In case of overdose, patients should be closely monitored for signs or symptoms of adverse drug reactions, and appropriate symptomatic treatment should be instituted immediately.

Unopened vial

3 years.

After opening

Once opened, the medicinal product should be diluted and infused immediately (see section 6.6 for instructions on dilution of the medicinal product before administration).

After preparation of solution for infusion

Tevimbra does not contain a preservative. Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C to 8°C. The 24 hours include storage of the diluted solution under refrigeration (2°C to 8°C) for no more than 20 hours, time required for returning to room temperature (25°C or below) and time to complete the infusion within 4 hours.

From a microbiological point of view, unless the method of dilution precludes the risk of microbial contamination, the product should be used immediately.

If not used immediately, in-use storage times and conditions are the responsibility of the user. The diluted solution must not be frozen.

Store in a refrigerator (2°C-8°C).

Do not freeze.

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

For storage conditions after dilution of the medicinal product, see section 6.3.

10 ml of Tevimbra concentrate is provided in a clear Type 1 glass vial, with a grey chlorobutyl stopper with FluroTec coating and seal cap with a flip-off button.

Tevimbra is available in unit packs containing 1 vial and in multipacks containing 2 (2 packs of 1) vials.

The diluted solution for infusion should be prepared by a healthcare professional using aseptic technique.

Preparation of solution for infusion:

• Two Tevimbra vials are required for each dose.
• Remove the vials from the refrigerator, taking care not to shake them.
• Inspect each vial visually for particulate matter and discolouration prior to administration. The concentrate is a clear to slightly opalescent, colourless to slightly yellowish solution. Do not use a vial if the solution is cloudy, or if visible particles or discolouration are observed.
• Invert the vials gently without shaking. Withdraw the solution from the two vials (a total of 200 mg in 20 ml) into a syringe and transfer into an intravenous infusion bag containing sodium chloride 9 mg/ml (0.9%) solution for injection, to prepare a diluted solution with a final concentration ranging from 2 to 5 mg/ml. Mix diluted solution by gentle inversion to avoid foaming or excessive shearing of the solution.

Administration:

• Administer the diluted Tevimbra solution by infusion through an intravenous administration line with a sterile, non-pyrogenic, low-protein-binding 0.2 micron or 0.22 micron in-line or add-on filter with a surface area of approximately 10 cm².
• The first infusion should be delivered over 60 minutes. If well tolerated, subsequent infusions may be administered over 30 minutes.
• Other medicinal products should not be co-administered through the same infusion line.
• Tevimbra must not be administered as an intravenous push or single bolus injection.
• The intravenous line must be flushed at the end of the infusion.
• Discard any unused portion left in the vial.
• Tevimbra vials are for single use only.

Disposal:

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.