EBVALLO Dispersion for injection Ref.[50629] Active ingredients: Tabelecleucel

Ebvallo should be administered under the supervision of a physician experienced in the treatment of cancer in a controlled setting where adequate facilities for handling of adverse reactions, including those requiring urgent measures, are available.

Posology

Treatment consists of multiple doses for injection containing a dispersion of viable T cells in one or more vials.

The recommended dose of Ebvallo contains 2 × 10⁶ viable T cells per kg of the patient’s body weight.

Dose calculations

Patient weight (kg) × target dose (2 × 10⁶ viable T cells/kg) = Viable T cells to be administered

Viable T cells to be administered ÷ Actual concentration (viable T cells/mL)* = Volume of thawed cell dispersion required (mL)**

^* See the accompanying Lot Information Sheet (LIS) and carton for information pertaining to the actual concentration of cells per vial.
^** Volume of thawed cell dispersion requires dilution, see section 6.6.

Note: The viable T-cell concentration on the LIS and carton is the actual concentration of each vial. This may be different than the nominal concentration listed on the vial label, which should not be used for dose preparation calculations. Each vial contains 1 mL deliverable volume.

The medicinal product is administered over multiple 35-day cycles, during which patients receive Ebvallo on days 1, 8 and 15, followed by observation through day 35. A response is assessed at approximately day 28.

The number of cycles of the medicinal product to be administered is determined by the response to treatment shown in Table 1. If a complete or partial response is not obtained, patients may be switched to an Ebvallo lot with a different HLA restriction (up to 4 different restrictions) selected from the existing product inventory.

Table 1. Treatment algorithm:

^a Complete response at the end of a cycle followed by partial response or other response at any subsequent cycle is considered progressive disease.

Monitoring

It is recommended to monitor vital signs immediately prior to each Ebvallo injection, within 10 minutes following the conclusion of the injection and 1 hour after the initiation of the injection (see section 4.4).

Missed dose

If a patient misses a dose, the missed dose should be given as soon as reasonably possible.

Special populations

Elderly

No dose adjustment is required in patients ≥65 years of age (see section 5.1). Ebvallo should be used with caution in elderly (see section 4.4).

Hepatic and renal impairment

No dose adjustment is required for patients with hepatic or renal impairment (see section 5.2).

Paediatric population

Posology and administration in paediatric patients 2 years of age and older are the same as for adult patients.

The safety and efficacy of Ebvallo in paediatric patients below 2 years of age have not yet been established. No data are available.

Method of administration

Ebvallo is for intravenous use only.

Administration:

• Administer Ebvallo as a single dose intravenously after dilution.
• Connect the final medicinal product syringe to the patient’s intravenous catheter and inject over 5 to 10 minutes.
• Once Ebvallo is fully dispensed from the syringe, flush the intravenous line with ≥10 mL of sodium chloride 9 mg/mL (0.9%) solution for injection.

For detailed instructions on preparation, accidental exposure and disposal of the medicinal product, see section 6.6.

There are no data regarding overdose with Ebvallo.

4 years when stored in the vapour phase of liquid nitrogen at ≤ -150°C. The drug product lot manufacturing date (MFD) is provided on the vial. The expiry date is provided on the Lot Information Sheet (LIS) and carton.

The medicinal product should be thawed and diluted within 1 hour from the start of thaw. Administration must be completed within 3 hours from the start of thaw (see section 6.6).

Store between 15°C to 25°C after thawing and dilution are complete. Protect product from light. Do not refreeze. Do not irradiate.

The Ebvallo carton must be stored in the vapour phase of liquid nitrogen at ≤ -150°C until immediately prior to preparation for administration. The liquid nitrogen vapour shipper provided can maintain the appropriate temperature from the sealing of the shipper until the scheduled dose. The temperature should be monitored regularly. Three temperature excursions up to -80 °C are permittable.

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

Ebvallo is supplied in a cyclo-olefin copolymer 2 mL stoppered vials with a thermoplastic elastomer closure containing 1 mL deliverable volume of cell dispersion.

The carton contains a variable number of vials (between 1 vial and 6 vials) according to the patientspecific dose required.

Precautions to be taken before handling or administering the medicinal product

This medicinal product contains human blood cells. Healthcare professionals handling Ebvallo must take appropriate precautions (wearing gloves and glasses) to avoid potential transmission of infectious diseases.

Preparation prior to administration

The patient’s identity must match the patient identifiers (APIN and Institution Patient ID) on the accompanying Ebvallo Lot Information Sheet (LIS) and carton. Product-patient reconciliation must be performed by matching information on the LIS against 1) the carton (matching APIN and FDP Number) and against 2) the vial label (matching Lot Number and Donor ID). Do not prepare or administer Ebvallo if the patient’s identity or the product-patient reconciliation cannot be confirmed. Prior to thawing, ensure that the required dose calculations are completed (see section 4.2), all materials needed to prepare the dose are available, and the patient is onsite and has been clinically evaluated.

Materials required for dose preparation:

• Sterile syringes:
  • Dosing syringe (select a syringe size that can accommodate required diluent [see Prepare the diluent] and cell dispersion volume)
  • Product draw syringe [select a syringe size that can appropriately measure and will accommodate the calculated volume of cell dispersion needed (see section 4.2)]
• Diluent (sterile, non-pyrogenic multiple electrolytes solution for injection Type 1 pH 7.4)
• Aseptic devices for transferring product (18-gauge unfiltered syringe needles, Luer Lock adapter, Luer Lock cap)

Prepare the diluent:

• Select the appropriate diluent volume (30 mL for patient weight ≤40 kg; 50 mL for patient weight >40 kg).
• Aseptically draw the selected volume of diluent into the dosing syringe. Thawing
• The thawing process of Ebvallo can begin after the patient is onsite and has been clinically evaluated.
• Remove the carton from the vapour phase of liquid nitrogen at ≤ -150°C.
• Frozen vial(s) of Ebvallo should be placed inside a sterile bag during thawing to protect from contamination and thawed upright in a 37°C water bath or dry thawing chamber.
• Record the start of thaw time. While the medicinal product thaws, swirl the product vial(s) gently until fully thawed by inspection (approximately 2.5 to 15 minutes). Product should be removed from the thawing device immediately upon completion of thaw.
• Dose preparation must be completed within 1 hour from the start of thaw.
• Thawed or prepared product must not be refrozen. Do not irradiate.

Dilution and dose preparation:

• Gently invert the vial(s) until the cell dispersion is mixed.
• Aseptically withdraw the required cell dispersion volume from the provided product vial(s) into the product draw syringe using an 18-gauge unfiltered needle (see section 4.2).
• Aseptically transfer the cell dispersion from the product draw syringe to the dosing syringe (previously filled with diluent). Ensure entire content is transferred from the product draw syringe.
• Inspect the diluted Ebvallo in the dosing syringe: cell dispersion should appear as a translucent, hazy solution. If visible clumps appear, continue to gently mix the solution. Small clumps of cellular material should disperse with gentle manual mixing.
• Maintain Ebvallo between 15°C to 25°C during dose preparation and administration. Dose preparation must be completed within 1 hour from the start of thaw. Administration must be completed within 3 hours from the start of thaw.

Measures to take in case of accidental exposure

In case of accidental exposure, local guidelines on handling of human-derived material should be followed, which may include washing of the contaminated skin and removal of contaminated clothes. Work surfaces and materials which have potentially been in contact with Ebvallo must be decontaminated with appropriate disinfectant.

Precautions to be taken for the disposal of the medicinal product

Unused medicinal product and all material that has been in contact with Ebvallo (solid and liquid waste) must be handled and disposed of as potentially infectious waste in accordance with local guidelines on handling of human-derived material.