KIMMTRAK 100 micrograms/0.5 ml concentrate for infusion solution

Introduction

Package Leaflet: Information for the Patient

KIMMTRAK 100 micrograms/0.5 ml concentrate for solution for infusion

tebentafusp

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is KIMMTRAK and what is it used for
2. What you need to know before you are given KIMMTRAK
3. How KIMMTRAK is given
4. Possible side effects
5. Storage of KIMMTRAK
6. Contents of the pack and other information

1. What is KIMMTRAK and what is it used for

KIMMTRAK contains the active substance tebentafusp. Tebentafusp is a cancer medicine made up of two different proteins joined together. One of these proteins recognises an antigen (the target protein) called “gp100” and binds to it. In uveal melanoma cancer cells, there are high levels of gp100. The other protein recognises a protein called CD3 and binds to it. The protein CD3 is found on certain cells of the body's immune system. By binding to gp100 and CD3, KIMMTRAK activates the immune system to recognise and destroy cancer cells.

KIMMTRAK is used to treat adults with a rare type of eye cancer called uveal melanoma. The medicine is used when the uveal melanoma has grown despite local treatment or when it has spread to other parts of the body.

2. What you need to know before you are given KIMMTRAK

Do not useKIMMTRAK if you are allergicto tebentafusp or any of the other ingredients of this medicine (listed in section 6). If you are not sure if you are allergic to any of the ingredients, talk to your doctor or nurse before you are given KIMMTRAK.

Warnings and precautions

Talk to your doctor or nurse before you start receiving KIMMTRAK about all the diseases you have, especially if you have:

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

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

Before you are given KIMMTRAK, tell 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.

Tell your doctor or nurse immediately or seek urgent medical attention if you get any of the following side effects during or after treatment:

• fever, dizziness or mild lightheadedness. These can be symptoms of a serious condition called cytokine release syndrome. Other symptoms of cytokine release syndrome are difficulty breathing, nausea, vomiting, fatigue, muscle pain, joint pain, swelling, low blood pressure, fast heart rate or headache.
• itching of the skin, rash, intense hives (itchy lumps under the skin), skin peeling, swelling of the body and/or skin around the eyes, which can be symptoms of skin reactions.
• heart problems such as a fast or irregular heartbeat or a change in the heart's electrical activity that can cause serious irregular heart rhythms which can be noticed by palpitations, difficulty breathing, mild lightheadedness or dizziness and chest pain.

Your doctor or nurse will check for signs and symptoms of these reactions during and after each dose. If you have serious problems, it is possible that the treatment will be temporarily stopped and restarted when you are feeling better.

Children and adolescents

Do not give this medicine to children under 18 years of age, as there is limited information on its efficacy in this age group.

Other medicines and KIMMTRAK

Tell your doctor if you are taking, have recently taken or might take any other medicines.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Pregnancy

KIMMTRAK must not be used during pregnancy unless you and your doctor agree that the benefit of taking the medicine is greater than the possible risks. If you are a woman who can become pregnant, your doctor or nurse will do a pregnancy test before you start treatment with KIMMTRAK. If you become pregnant during treatment with KIMMTRAK, tell your doctor or nurse immediately.

Contraception

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

Breastfeeding

You must not breastfeed during treatment with KIMMTRAK. It is not known whether KIMMTRAK passes into breast milk.

Driving and using machines

KIMMTRAK is unlikely to affect your ability to drive or use machines. If you do not feel well while being treated with this medicine, do not drive or use machinery until you are feeling better.

KIMMTRAK contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per millilitre, which is essentially “sodium-free”.

3. How KIMMTRAK is given

This medicine will be given to you by a doctor or nurse in a hospital or outpatient clinic.

You may be given an infusion of fluids (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 give you KIMMTRAK as an infusion (drip) into a vein (intravenously) over 15 to 20 minutes. You will be given KIMMTRAK once a week, for as long as your doctor thinks it is helping you.

The recommended dose of KIMMTRAK is:

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

Once a week from then on: 68 micrograms

The first three doses will be given to you in a hospital. Your doctor or nurse will check for any side effects during treatment and for at least 16 hoursafter each dose.

If the first three doses do not cause you any serious or uncontrolled side effects, the following doses will be given to you in an outpatient clinic. Your doctor or nurse will check for any side effects during treatment and for at least 60 minutes after each dose. If you have been treated with KIMMTRAK in an outpatient clinic for at least 3 months without a break of more than 2 weeks, the monitoring after each dose can 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 further questions on the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor or nurse immediately or seek urgent medical attention if you get any of the following very common side effects during or after treatment:

• Fever, dizziness or mild lightheadedness. These can be symptoms of a serious condition called “cytokine release syndrome”. Other symptoms of cytokine release syndrome are difficulty breathing, nausea, vomiting, fatigue, muscle pain, joint pain, swelling, low blood pressure, fast heart rate or headache. These symptoms usually occur after the first three infusions.
• Itching of the skin, rash, intense hives (itchy lumps under the skin), skin peeling, swelling of the body and/or skin around the eyes, which can be symptoms of skin reactions. These symptoms usually occur after the first three infusions.
• Heart problems such as a fast or irregular heartbeat or a change in the heart's electrical activity that can cause serious irregular heart rhythms which can be noticed by palpitations, difficulty breathing, mild lightheadedness or dizziness and chest pain.

Other side effects:

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

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

• Decreased appetite
• Numbness, tingling or itching in any part of the body
• Cough
• Diarrhoea
• Constipation
• Indigestion
• Stomach pain
• Chills
• Sleep disorders (insomnia)
• Flu-like symptoms
• Difficulty sleeping
• Flush
• High blood pressure
• Dry skin
• Changes in skin colour
• Redness of the skin
• 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 haemoglobin levels in the blood
• Increased liver enzyme levels in the blood, which can be a sign of liver problems
• Increased bilirubin levels in the blood, which can be a sign of liver problems
• Increased pancreatic enzyme lipase levels in the blood, which can be a sign of pancreas problems
• Decreased white blood cell count
• Back pain or pain in the arms or legs

Common(may affect up to 1 in 10 people)

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

Uncommon(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
• Chest pain or discomfort, which can be a sign of heart problems
• Heart failure (difficulty breathing, chest discomfort, swelling of the legs and ankles)
• Changes in the heart's electrical activity that can cause serious irregular heart rhythms

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of KIMMTRAK

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

Do not use this medicine after the expiry date which is stated on the vial label and carton after EXP. The expiry date is the last day of the month shown.

Unopened vials should be stored in a refrigerator (2°C - 8°C).

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

If not used immediately, the prepared infusion can be stored below 30°C for up to 4 hours or in a refrigerator (2°C - 8°C) for up to 24 hours from the time of preparation/dilution until the end of administration.

Do not use this medicine if you notice visible signs of deterioration (e.g. particles, colour change).

Do not store unused medicine for reuse. Disposal of unused medicine and all materials that have come into contact with it should be done in accordance with local regulations. This will help protect the environment.

6. Container contents and additional information

KIMMTRAK composition

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

Product appearance and container contents

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

The container size is 1 glass vial per box.

Marketing authorization holder

Immunocore Ireland Limited

Unit 1, Sky Business Centre

Dublin 17, D17 FY82

Ireland

Manufacturer

Baxter Oncology GmbH

Kantstraße 2

33790 Halle/Westfalen

Germany

Date of last revision of this prospectus:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

On the European Medicines Agency website, this prospectus can be found in all languages of the European Union/European Economic Area.

This information is intended solely for healthcare professionals:

Important:Consult the Summary of Product Characteristics or Package Leaflet before using this medicinal product.

General precautions

The infusion solution should be prepared by a healthcare professional using adequate aseptic technique throughout the handling of this medicinal product.

Closed system drug transfer devices (CSTD) should not be used for the preparation of the KIMMTRAK infusion solution dose.

Whenever the solution and container permit, parenteral drugs and infusion bags should be inspected visually for particulate matter or color change prior to administration.

Preparation

KIMMTRAK should be diluted prior to intravenous administration. Each vial of KIMMTRAK is intended for single use. DO NOT shake the KIMMTRAK vial.

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

• Sterile 1 ml syringes with 2 decimal places 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 9 mg/ml (0.9%) sodium chloride injectable solution.

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

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

Dilution and administration

A 2-step process must be followed for the preparation of the final KIMMTRAK dose:

Step 1: Preparation of the infusion bag

Using aseptic technique, prepare the infusion bag as follows:

1. With a 1 ml syringe and a sterile needle, withdraw the calculated volume of human albumin (see Table 1 below) and add it to the 100 ml infusion bag containing the 9 mg/ml (0.9%) sodium chloride injectable solution, to achieve a final human albumin concentration of between 225 µg/ml and 275 µg/ml.

Table 1: Examples of human albumin concentrations and acceptable volumes to withdraw

1. Perform the following steps to homogenize the diluted solution:
   1. Invert the infusion bag so that the entry port is at the top of the bag and gently tap the side of the tube of the port to ensure that any remaining solution passes into the main solution.
   2. Mix carefully by rotating the bag longitudinally 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. With a 1 ml syringe and a sterile needle, withdraw the required volume of KIMMTRAK 100 micrograms/0.5 ml according to the necessary dose (as shown in Table 2 below) and add it to the prepared 100 ml infusion bag containing the 9 mg/ml (0.9%) sodium chloride injectable solution and human albumin.
2. DO NOT flush the needle or syringe after transfer. Discard 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, should be used. Administer the entire contents of the KIMMTRAK infusion bag to the patient.
• After completing the infusion with KIMMTRAK, flush the infusion line with an adequate volume of sterile 9 mg/ml (0.9%) sodium chloride injectable solution to ensure that the entire contents of the infusion bag are administered. KIMMTRAK should not be administered as a slow intravenous injection or bolus. Do not mix KIMMTRAK with other medicinal products or administer other medicinal products through the same intravenous line.

Storage of the prepared infusion bag

• KIMMTRAK does not contain preservatives. The prepared infusion bag should be administered within 4 hours of preparation; this includes the duration of the infusion. Within this 4-hour interval, the KIMMTRAK infusion bag should be stored below 30°C.
• If not used immediately, the KIMMTRAK infusion bag should be stored in a refrigerator between 2°C and 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 should not be refrigerated again. Discard the unused KIMMTRAK solution when the recommended storage time is exceeded.