Prospect: information for the patient

KIMMTRAK 100 micrograms/0.5 ml concentrate for solution for infusion

tebentafusp

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You may contribute by reporting any adverse effects you experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to take this medicine, because it contains important information for you.

• Keep this prospect, as you may need to refer to it again.
• If you have any questions, consult your doctor or nurse.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section 4.

KIMMTRAK contains the active ingredienttebentafusp. Tebentafusp is a cancer medication formed by two different proteins fused together. One of those proteins recognizes an antigen (the target protein) called “gp100” and binds to it. In uveal melanoma cancer cells, there are high concentrations of gp100. The other protein recognizes a protein called CD3 and binds to it. The CD3 protein is present in certain immune system cells of the body. By binding to gp100 and CD3, KIMMTRAK activates the immune system to recognize cancer cells and destroy them.

KIMMTRAK is used to treat adults with a rare eye cancer called “uveal melanoma”. The medication is used when uveal melanoma has increased despite local treatment or has spread to other parts of the body.

No useKIMMTRAK if you areallergicto tebentafusp or to any of the other components of this medication (listed in section 6). If you are unsure if you are allergic to any of the components, consult your doctor or nurse before receiving KIMMTRAK.

Warnings and precautions

Consult your doctor or nurse before starting KIMMTRAK about all the conditions you have, especially if you have the following:

• heart problems, including a change in the heart's electrical activity (prolongation of the QT interval)

Your doctor may perform a blood test called HLA genotyping to determine if KIMMTRAK is suitable for you.

Before KIMMTRAK is administered, inform your doctor if you are taking corticosteroids to treat adrenal insufficiency (also known as "Addison's disease"). Your doctor may need to adjust your corticosteroid dose while you are being treated with KIMMTRAK.

Inform your doctor or nurse immediately or seek urgent medical assistance if you experience any of the following adverse effects during or after treatment:

• fever, dizziness, or light-headedness. These may be symptoms of a serious condition calledcytokine release syndrome. Other symptoms of cytokine release syndrome include difficulty breathing, nausea, vomiting, fatigue, muscle pain, joint pain, swelling, low blood pressure, rapid heart rate, or headache.
• itching, hives, intense rashes (bumps under the skin), skin peeling, or swelling of the body and/or skin around the eyes, which may be symptoms ofskin reactions.
• heart problems such as a rapid or irregular heartbeat or a change in the heart's electrical activity that can cause severe irregular heart rhythms that may manifest as palpitations, difficulty breathing, light-headedness, or dizziness, and chest pain.

Your doctor or nurse will monitor the appearance of signs and symptoms of these reactions during and after each dose. If you experience severe problems, treatment may be temporarily interrupted and resumed when you are feeling better.

Children and adolescents

Do not administer this medication to children under 18 years of age, as the information regarding efficacy in this age group is limited.

Other medications and KIMMTRAK

Inform your doctor if you are taking, have taken recently, or may need to take any other medication.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, believe you may be pregnant, or intend to become pregnant, consult your doctor before using this medication.

Pregnancy

KIMMTRAK should not be used during pregnancy, unless you and your doctor agree that the benefits of taking the medication outweigh the potential risks. If you are a woman who may become pregnant, your doctor or nurse will perform a pregnancy test before starting treatment with KIMMTRAK. If you become pregnant during treatment with KIMMTRAK, inform your doctor or nurse immediately.

Contraception

If you are a fertile woman, you should use an effective contraceptive method to avoid becoming pregnant during treatment with KIMMTRAK and for at least 1 week after the last dose. Consult your doctor about the most suitable contraceptive methods.

Breastfeeding

You should not breastfeed during treatment with KIMMTRAK. It is unknown whether KIMMTRAK passes into breast milk.

Driving and operating machinery

It is unlikely that KIMMTRAK will affect your ability to drive or operate machinery. If you do not feel well while being treated with this medication, do not drive or operate machinery until you feel better.

KIMMTRAK contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per milliliter; it is essentially "sodium-free".

A doctor or nurse will administer this medication in a hospital or outpatient setting.

They may administer a fluid infusion (drip) before each KIMMTRAK infusion to help prevent low blood pressure due to cytokine release syndrome (see sections 2 and 4).

Your doctor or nurse will administer KIMMTRAK through an intravenous infusion (drip) in a vein for 15 to 20 minutes. They will administer KIMMTRAKonce a week, for as long as your doctor considers the treatment to be beneficial.

The recommended dose of KIMMTRAK is:

• Day 1: 20 micrograms
• Day 8: 30 micrograms
• Day 15: 68 micrograms

Once a week thereafter: 68 micrograms

They will administer the first three doses in a hospital. They will monitor for any adverse effects during treatment and forat least 16 hoursafter each dose.

If the first three doses do not cause any severe or uncontrolled adverse effects, they will administer the subsequent doses in an outpatient setting. They will monitor for any adverse effects during treatment and for at least 60 minutes after each dose. If you have received KIMMTRAK treatment in an outpatient setting for at least 3 months without an interruption of more than 2 weeks, the monitoring after each dose may be reduced to at least 30 minutes.

If you miss a scheduled dose of KIMMTRAK, contact your doctor or nurse as soon as possible to reschedule.

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Inform your doctor or nurse immediately or seek urgent medical assistance if you experience any of the following very common side effects during or after treatment:

• Fever, dizziness, or mild lightheadedness. These may be symptoms of a serious condition called "cytokine release syndrome." Other symptoms of cytokine release syndrome include difficulty breathing, nausea, vomiting, fatigue, muscle pain, joint pain, swelling, low blood pressure, rapid heart rate, or headache. These symptoms occur mainly after the first three infusions.
• Itching, rash, intense hives (bumps with itching under the skin), skin peeling, body swelling, and/or facial swelling around the eyes, which may be symptoms of skin reactions. These symptoms occur mainly after the first three infusions.
• Cardiac problems such as a rapid or irregular heartbeat or a change in heart electrical activity that can cause severe irregular heart rhythms that may manifest as palpitations, difficulty breathing, mild dizziness, or chest pain.

Other side effects:

Inform your doctor if you notice any of the following side effects:

Very common(may affect more than 1 in 10 people)

• Loss of appetite
• Tickling, itching, or numbness in any part of the body
• Cough
• Diarrhea
• Constipation
• Indigestion
• Stomach pain
• Chills
• Sleep disturbances (insomnia)
• Flu-like symptoms
• Inability to sleep
• Redness of the skin
• High blood pressure
• Dry skin
• Changes in skin color
• Facial flushing
• Decreased phosphate levels in the blood
• Decreased magnesium levels in the blood
• Decreased sodium levels in the blood
• Decreased calcium levels in the blood
• Decreased potassium levels in the blood
• Decreased hemoglobin levels in the blood
• Increased levels of liver enzymes in the blood, which may be a sign of liver problems
• Increased levels of bilirubin in the blood, which may be a sign of liver problems
• Increased levels of pancreatic lipase enzyme in the blood, which may be a sign of pancreas problems
• Decreased white blood cell count in the blood
• Back pain or pain in the arms or legs

Common(may affect up to 1 in 10 people)

• Upper respiratory tract infection
• Pain in the mouth and throat
• Hair loss
• Excessive sweating at night
• Anxiety
• Changes in taste
• Changes or irregularity in heart rhythm
• Difficulty breathing
• Muscle spasms
• Increased levels of pancreatic amylase enzyme in the blood
• Increased levels of creatinine in the blood, which may be a sign of kidney problems
• Increased levels of gamma-glutamyltransferase liver enzyme in the blood
• Increased white blood cell count in the blood
• Increased levels of liver enzymes in the blood
• Increased levels of alkaline phosphatase in the blood
• Increased levels of glucose in the blood

Rare(may affect up to 1 in 100 people)

• Increased levels of potassium, phosphate, and uric acid in the blood, which are signs of cancer cell death
• Discomfort or pain in the chest, which may be a sign of heart problems
• Heart failure (difficulty breathing, chest pain, swelling of the legs and ankles)
• Changes in heart electrical activity that can cause severe irregular heart rhythms

Reporting side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the vial label and the box after CAD. The expiration date is the last day of the month indicated.

Unopened vials should be stored between 2 °C and 8 °C.

Keep the vial in the outer packaging to protect it from light.

If not used immediately, the prepared infusion can be stored below 30 °C for up to 4 hours or between 2 °C and 8 °C for 24 hours from the time of preparation/dilution to the end of administration.

Do not use this medication if you observe visible signs of deterioration (i.e., particles, color change).

Do not store unused medication for re-use. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations. This will help to protect the environment.

Composition of KIMMTRAK

• The active ingredient is tebentafusp. A vial of 0.5 ml of concentrate contains 100 micrograms of tebentafusp.
• The other components are: citric acid monohydrate (E330), sodium hydrogen phosphate (E339), mannitol (E421), trehalose, polisorbate 20 (E432) and water for injection (see section 2).

Appearance of the product and contents of the pack

KIMMTRAK concentrate for solution for infusion (sterile concentrate) is a transparent, colourless or slightly yellowish solution contained in a single-dose vial.

The pack size is 1 vial of glass per carton.

Marketing authorisation holder

Immunocore Ireland Limited

Unit 1, Sky Business Centre

Dublin 17, D17 FY82

Ireland

Manufacturer

Baxter Oncology GmbH

Kantstraße 2

33790 Halle/Westfalen

Germany

Last update of the leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency.

This information is intended for healthcare professionals only:

Important:Consult the SmPC or the Package Leaflet before using this medicine.

General precautions

The infusion solution must be prepared by a healthcare professional using an appropriate aseptic technique throughout the handling of this medicine.

Do not use closed system transfer devices (CSTD) for the preparation of the KIMMTRAK infusion solution.

Whenever the solution and the container permit, parenteral medicines and infusion bags should be inspected visually for particles and any change in colour before administration.

Preparation

KIMMTRAK must be diluted before administration by intravenous route. Each vial of KIMMTRAK is intended for single use.DO NOT SHAKE the vial of KIMMTRAK.

Ensure that you have the following material before preparing KIMMTRAK for administration:

• 1 ml sterile syringes with a 2 decimal graduation.
• Sterile needles.
• Human albumin; concentration according to local availability. Local concentrations are, among others, 4% (40 g/l), 5% (50 g/l), 20% (200 g/l) and 25% (250 g/l).
• A 100 ml infusion bag containing a 0.9% sodium chloride injection solution.

• The infusion bag must be made of polyolefins (PO) (such as polyethylene [PE] and polypropylene [PP]) or of chlorinated polyvinyl chloride (PVC).

• A sterile, non-pyrogenic and low protein-binding in-line filter, 0.2 microns for the administration of the final infusion bag.

Dilution and administration

A two-step process is required to prepare the final dose of KIMMTRAK:

Step 1: Preparation of the infusion bag

Using an aseptic technique, prepare the infusion bag as follows:

1. Using a 1 ml syringe and a sterile needle, withdraw the calculated volume of human albumin from the syringe (see Table 1 below) and add it to the 100 ml infusion bag containing the 0.9% sodium chloride injection solution to achieve a final concentration of human albumin of between 225 µg/ml and 275 µg/ml.

Table 1: Examples of human albumin concentrations and acceptable volumes to add to the 100 ml infusion bag to obtain a concentration of human albumin of between 225 µg/ml and 275 µg/ml

1. Perform the following steps to homogenize the diluted solution:
   1. Invert the infusion bag so that the inlet port is at the top of the bag and gently tap the side of the tube to ensure that any remaining solution passes into the main solution.
   2. Mix carefully by rotating the bag 360 degrees from the inverted position at least 5 times.DO NOT SHAKE the infusion bag.
   3. Repeat steps (i) and (ii) three more times.

Step 2: Preparation of KIMMTRAK infusion solution

1. Using a 1 ml syringe and a sterile needle, withdraw the required volume of KIMMTRAK 100 micrograms/0.5 ml according to the required dose (see Table 2 below) and add it to the prepared 100 ml infusion bag containing the 0.9% sodium chloride injection solution and human albumin.
2. DO NOT irrigate the needle or syringe after transfer. Dispose of the vial containing the unused portion of KIMMTRAK according to local regulations. Do not prepare more than one dose with the vial.

Table 2: Volumes of KIMMTRAK required to add to the infusion bag

1. Mix the infusion bag following the same process described in Step 1b.

Administration

• Administer KIMMTRAK only as an intravenous infusion.
• Administer the infusion immediately over 15 to 20 minutes through a separate intravenous line. A sterile, non-pyrogenic and low protein-binding in-line filter, 0.2 microns must be used. Administer the entire contents of the KIMMTRAK infusion bag to the patient.
• After completing the KIMMTRAK infusion, irrigate the infusion line with an appropriate volume of sterile 0.9% sodium chloride injection solution to ensure that the entire contents of the infusion bag are administered. KIMMTRAK must not be administered as a slow intravenous injection or as a bolus. Do not mix KIMMTRAK with other medicines or administer other medicines through the same intravenous line.

Storage of the prepared infusion bag

• KIMMTRAK does not contain preservatives. The prepared infusion bag must be administered within 4 hours of preparation; this includes the duration of the infusion. Within this 4-hour interval, the KIMMTRAK infusion bag must be stored below 30°C.
• If not used immediately, the KIMMTRAK infusion bag must be stored in the refrigerator at 2°C to 8°C for a maximum of 24 hours from the time of preparation; this includes the time to bring the infusion bag to room temperature and the duration of the infusion.
• Once removed from the refrigerator, the KIMMTRAK infusion bag must not be re-refrigerated. Dispose of the unused KIMMTRAK solution when the recommended storage time is exceeded.