ELAHERE Concentrate for solution for infusion Ref.[113939] Active ingredients: Mirvetuximab soravtansine

ELAHERE must be initiated and supervised by a physician experienced in the use of anticancer medicinal products.

Patient selection

Eligible patients should have FRα tumour status defined as ≥75% viable tumour cells demonstrating moderate (2+) and/or strong (3+) membrane staining by immunohistochemistry (IHC), assessed by a CE-marked in vitro diagnostic (IVD) with the corresponding intended purpose. If a CE-marked IVD is not available, an alternative validated test should be used.

Posology

The recommended dose of ELAHERE is 6 mg/kg adjusted ideal body weight (AIBW) administered once every 3 weeks (21-day cycle) as an intravenous infusion until disease progression or unacceptable toxicity. Dosing based on AIBW reduces exposure variability for patients who are either underweight or overweight.

The total dose of ELAHERE is calculated based on each patient’s AIBW using the following formula:

AIBW = Ideal Body Weight (IBW [kg]) + 0.4*(Actual weight [kg] – IBW)

Female IBW [kg] = 0.9*height [cm] – 92

For a female patient who is 165 cm in height and 80 kg in weight:

Pre-medication

Pre-medication for infusion related reactions (IRRs), nausea, and vomiting

Administer the pre-medications in Table 1 prior to each infusion of ELAHERE to reduce the incidence and severity of IRRs, nausea, and vomiting.

Table 1. Pre-medication prior to each ELAHERE infusion:

For patients experiencing nausea and/or vomiting, additional antiemetics may be considered thereafter as needed.

For patients who experience an IRR Grade ≥2, additional pre-medication with dexamethasone 8 mg two times a day (BID) (or equivalent) the day before ELAHERE administration should be considered.

Ophthalmic exam and pre-medication

Ophthalmic exam: An ophthalmic exam including visual acuity and slit lamp exam should be conducted before the initiation of ELAHERE and if a patient develops any new or worsening ocular symptoms prior to the next dose. In patients with ≥ Grade 2 ocular adverse reactions, additional ophthalmic exams should be conducted at a minimum of every other cycle and as clinically indicated until resolution or return to baseline.

Ophthalmic topical steroids: For patients found to have signs of ≥ Grade 2 corneal adverse reactions (keratopathy) on slit lamp examination, secondary prophylaxis with ophthalmic topical steroids is recommended for subsequent cycles of ELAHERE, unless the patient’s eye care professional determines that the risks outweigh the benefits of such therapy.

• Patients should be instructed to use steroid eye drops on the day of infusion and through the next 7 days of each subsequent cycle of ELAHERE (see Table 3).
• Patients should be advised to wait at least 15 minutes after ophthalmic topical steroid administration before instilling lubricating eye drops.

During treatment with ophthalmic topical steroids the measurement of intraocular pressure and an examination with slit lamp should be carried out regularly.

Lubricating eye drops: It is recommended to instruct patients to use lubricating eye drops throughout treatment with ELAHERE.

Dose modifications

Before the start of each cycle, the patient should be advised to report any new or worsening symptoms to the treating physician or qualified individual.

In patients who develop new or worsening ocular symptoms, an ophthalmic exam should be conducted before dosing. The treating physician should review the patient’s ophthalmic examination report before dosing and determine the dose of ELAHERE based on the severity of findings in the most severely affected eye.

Table 2 and Table 3 provide dose reductions and modifications for adverse reactions. The schedule of administration should be maintained at a 3-week interval between the doses.

Table 2. Dose reduction schedule:

^* Permanently discontinue in patients who cannot tolerate 4 mg/kg AIBW.

Table 3. Dose modifications for adverse reactions:

^* Unless otherwise specified, National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

Special populations

Paediatric population

There is no relevant use of ELAHERE for the treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer in the paediatric population (see section 5.1).

Elderly

No dose adjustment of ELAHERE is recommended in patients ≥65 years of age (see section 5.2).

Renal impairment

No dose adjustment of ELAHERE is recommended for patients with mild to moderate renal impairment (creatinine clearance [CLcr] 30 to <90 mL/min). ELAHERE has not been evaluated in patients with severe renal impairment (CLcr 15 to <30 mL/min) or end-stage renal disease and the potential need for dose adjustment in these patients cannot be determined (see section 5.2).

Hepatic impairment

No dose adjustment of ELAHERE is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] and aspartate aminotransferase [AST] > ULN or total bilirubin >1 to 1.5 times ULN and any AST) (see section 5.2).

ELAHERE should be avoided in patients with moderate to severe hepatic impairment (total bilirubin >1.5 ULN with any AST).

Method of administration

ELAHERE is for intravenous infusion at a rate of 1 mg/min. If well tolerated after 30 minutes, the infusion rate can be increased to 3 mg/min. If well tolerated after 30 minutes at 3 mg/min, the infusion rate can be increased to 5 mg/min.

For incompatibilities, see section 6.2.

ELAHERE requires dilution with 5% glucose for intravenous infusion. For instructions on dilution of the medicinal product before administration, see section 6.6.

ELAHERE must be administered as an intravenous infusion only, using a 0.2 or 0.22 μm polyethersulfone (PES) in-line filter (see Special handling and disposal procedures in section 6.6).

Precautions to be taken before handling or administering the medicinal product

This medicinal product contains a cytotoxic component, which is covalently attached to the monoclonal antibody (see special handling and disposal procedures in section 6.6).

There is no known treatment/antidote available for overdose of mirvetuximab soravtansine. In case of overdose, patients must be closely monitored for signs or symptoms of adverse reactions and appropriate symptomatic treatment initiated.

Unopened vial:

5 years.

Diluted solution:

After dilution the chemical and physical stability has been demonstrated between 1 mg/mL and 2 mg/mL for 8 hours at 15°C–25°C or for 24 hours at 2°C–8°C followed by 8 hours at 15°C–25°C.

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 user.

Store upright 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.

Type I glass vial with a butyl rubber stopper and an aluminum seal with a royal blue polypropylene flip cap, containing 20 mL concentrate for solution.

Pack size of 1 vial.

ELAHERE is a cytotoxic medicinal product. Follow applicable special handling and disposal procedures.

Preparation:

• Calculate the dose (mg) (based on the patient’s AIBW), total volume (mL) of solution required, and the number of vials of ELAHERE needed (see section 4.2). More than one vial will be needed for a full dose.
• Remove the vials of ELAHERE from the refrigerator and allow to warm to room temperature.
• Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit. ELAHERE is a clear to slightly opalescent, colourless solution.
• The medicinal product should not be used if the solution is discoloured or cloudy, or if foreign particulate matter is present.
• Gently swirl and inspect each vial prior to withdrawing the calculated dose volume of ELAHERE for subsequent further dilution. Do not shake the vial.
• Using aseptic technique, withdraw the calculated dose volume of ELAHERE for subsequent further dilution.
• ELAHERE contains no preservatives and is intended for single dose only. Discard any unused solution remaining in the vial.

Dilution:

• ELAHERE must be diluted prior to administration with 5% glucose to a final concentration of 1 mg/mL to 2 mg/mL.
• ELAHERE is not compatible with sodium chloride 9 mg/mL (0.9%) solution for infusion. ELAHERE must not be mixed with any other medicinal products or intravenous fluids.
• Determine the volume of 5% glucose required to achieve the final diluted active substance concentration. Either remove the excess 5% glucose from a pre-filled intravenous bag or add the calculated volume of 5% glucose to a sterile empty intravenous bag. Then add the calculated dose volume of ELAHERE to the intravenous bag.
• Gently mix the diluted solution by slowly inverting the bag several times to assure uniform mixing. Do not shake or agitate.
• If the diluted infusion solution is not used immediately, store the solution in accordance with section 6.3. If refrigerated, allow the infusion bag to reach room temperature prior to administration. After refrigeration, administer diluted infusion solutions within 8 hours (including infusion time).
• Do not freeze the prepared infusion solution.

Administration:

• Inspect the ELAHERE intravenous infusion bag visually for particulate matter and discolouration prior to administration.
• Administer pre-medications prior to ELAHERE administration (see section 4.2).
• Administer ELAHERE as an intravenous infusion only, using a 0.2 or 0.22 μm polyethersulfone (PES) in-line filter. Do not substitute other membrane materials.
• Use of administration delivery devices containing Di-2-ethylhexyl phthalate (DEHP) should be avoided.
• Administer the initial dose as an intravenous infusion at the rate of 1 mg/min. If well tolerated after 30 minutes at 1 mg/min, the infusion rate can be increased to 3 mg/min. If well tolerated after 30 minutes at 3 mg/min, the infusion rate can be increased to 5 mg/min.
• If no infusion-related reactions occur with the previous dose, subsequent infusions should be started at the maximally tolerated rate and may be increased up to a maximum infusion rate of 5 mg/min, as tolerated.
• Following the infusion, flush the intravenous line with 5% glucose to ensure delivery of the full dose. Do not use any other intravenous fluids for flushing.

Disposal:

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