KIMMTRAK

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. This will allow for the rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What KIMMTRAK is and what it is used for

KIMMTRAK contains the active substance tebentafusp. Tebentafusp is an anticancer medicine
composed of two different proteins fused together. One of these proteins recognises and binds to a
target protein (antigen) called "Gp100". The Gp100 protein is present at high levels in cancerous cells of
uveal melanoma. The other protein recognises and binds to a protein called "CD3". CD3 protein is
present on certain cells of the body's immune system. By binding to both 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 uveal melanoma has progressed despite local treatment, or when it has spread
to other parts of the body.

2. What you should know before being given KIMMTRAK

Do not use KIMMTRAK if you are allergic to tebentafusp or to any of the other ingredients of this
medicine (listed in section 6). If you are unsure whether you are allergic to any of the ingredients,
please consult your doctor or nurse before receiving KIMMTRAK.
Warnings and precautions
Before you are given KIMMTRAK, inform your doctor or nurse about all your
medical conditions, especially if you have:
heart problems, including an abnormality in the heart's electrical activity (QT interval prolongation).
Your doctor may request a blood test called HLA genotyping before treatment to determine whether KIMMTRAK is suitable for you.
Before you are given KIMMTRAK, 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 during treatment with KIMMTRAK.
If you experience any of the following side effects during or after treatment, inform your
doctor or nurse immediately or seek urgent medical assistance:

• fever, dizziness, feeling faint. These could 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 heartbeat, or headache;
• skin itching, rash, severe hives (itchy, raised swellings under the skin), skin peeling or shedding, swelling of the body and/or skin around the eyes, which could be symptoms of skin reactions;
• heart problems such as rapid or irregular heartbeat or an abnormality in the heart's electrical activity that may cause serious heart rhythm disturbances, such as palpitations, shortness of breath, feeling faint or dizzy, or chest pain.

Your doctor or nurse will monitor you closely for any signs and symptoms of these reactions during and after each dose administration. If you develop severe problems, treatment may be temporarily interrupted and resumed once you feel better.
Children and adolescents
Do not administer this medicine to children under 18 years of age, as available information on its use in this age group is limited.
Other medicines and KIMMTRAK
Inform your doctor if you are currently taking, have recently taken, or might take any other
medicines.
Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding,
please consult your doctor before taking this medicine.
Pregnancy
KIMMTRAK must not be used during pregnancy unless you and your doctor agree that the benefit of treatment with this medicine outweighs the potential risks. If you are a woman of childbearing potential, your doctor or nurse will ask you to undergo 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 woman of childbearing potential, you must use effective contraceptive measures to avoid pregnancy during treatment with KIMMTRAK and for at least 1 week after receiving the last dose. Discuss with your doctor which contraceptive methods are most appropriate.
Breastfeeding
Do not breastfeed during treatment with KIMMTRAK. It is not known whether KIMMTRAK passes into breast milk.
Driving and using machines
It is unlikely that KIMMTRAK will affect your ability to drive or operate machinery. However, if you feel unwell during treatment with this medicine, wait until you feel well again before driving or operating machinery.
KIMMTRAK contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per mL and is therefore essentially ‘sodium-free’.

3. How KIMMTRAK is administered

This medicine will be administered to you by a doctor or nurse in a hospital or outpatient setting.
Before each KIMMTRAK infusion, you may be given an intravenous infusion (drip) of fluids to help prevent low blood pressure due to cytokine release syndrome (see sections 2 and 4).
KIMMTRAK will be administered by a doctor or nurse as an intravenous infusion (drip) lasting between 15 and 20 minutes. KIMMTRAK will be given once a week, for as long as your doctor considers that you are benefiting from the treatment.
The recommended dose of KIMMTRAK is:

• Day 1: 20 micrograms
• Day 8: 30 micrograms
• Day 15: 68 micrograms
  Subsequently, once a week: 68 micrograms

The first three doses will be administered in hospital. You will be monitored during treatment and for at least 16 hours after each dose to detect any adverse reactions.
If the first three doses do not cause you severe or unmanageable side effects, subsequent doses may be administered in an outpatient setting. You will be monitored 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 interruptions longer than 2 weeks, monitoring after each dose may be reduced to a minimum of 30 minutes.
If you miss an appointment for your next dose of KIMMTRAK, contact your doctor or nurse as soon as possible to schedule a new appointment.
If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you notice any of the following very common side effects during or after treatment, inform your doctor or nurse immediately or seek urgent medical assistance:

• fever, dizziness, feeling of emptiness in the head. These could 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 heartbeat or headache. These symptoms mostly occur after the first three infusions; itching of the skin, rash, severe hives (itchy swellings under the skin), skin peeling or flaking, swelling of the body and/or skin around the eyes, which could be symptoms of skin reactions. These symptoms mostly occur after the first three infusions; heart problems such as rapid or irregular heartbeat or changes in the heart's electrical activity that may cause serious heart rhythm disturbances, palpitations, shortness of breath, feeling of emptiness in the head or dizziness, or chest pain.

Other side effects
Tell your doctor if you notice any of the following side effects:
Very common side effects (may affect more than 1 in 10 people)

• reduced appetite
• tingling, numbness or pins and needles sensation anywhere in the body
• cough
• diarrhoea
• constipation
• indigestion
• stomach ache
• chills
• difficulty sleeping (insomnia)
• influenza-like symptoms
• inability to sleep
• skin redness
• high blood pressure
• dry skin
• changes in skin colour
• flushed skin
• decreased levels of phosphate in the blood
• decreased levels of magnesium in the blood
• decreased levels of sodium in the blood
• decreased levels of calcium in the blood
• decreased levels of potassium in the blood
• decreased haemoglobin levels in the blood
• increased levels of liver enzymes in the blood, which could indicate a liver problem
• increased levels of bilirubin in the blood, which could indicate a liver problem
• increased levels of the pancreatic enzyme lipase in the blood, which could indicate a pancreatic problem
• decreased levels of white blood cells in the blood
• back, arm or leg pain

Common side effects (may affect up to 1 in 10 people)

• nose and throat infection
• mouth and throat pain
• hair loss
• excessive night sweating
• anxiety
• changes in taste
• changes or irregularities in heart rhythm
• shortness of breath
• muscle spasms
• increased levels of the pancreatic enzyme amylase in the blood
• increased levels of creatinine in the blood, which may indicate a kidney problem
• increased levels of the liver enzyme gamma-glutamyltransferase in the blood
• increased levels of white blood cells 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

Uncommon side effects (may affect up to 1 in 100 people)

• increased levels of potassium, phosphate and uric acid in the blood, which is a sign of dying cancer cells
• discomfort or chest pain, which may indicate a heart problem
• heart failure (shortness of breath, chest discomfort, swelling of legs and ankles)
• disturbances in the heart's electrolyte activity that may lead to serious heart rhythm irregularities

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

5. How to store KIMMTRAK

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and on the carton after "Exp". The expiry date refers to the last day of that month.
Unopened vials must be stored at a temperature between 2 °C and 8 °C.
Keep the vial in the outer packaging to protect the medicine from light.
If not used immediately, the previously prepared infusion may be stored at a temperature below 30 °C for up to 4 hours, or at a temperature between 2 °C and 8 °C for 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. presence of particles, change in colour).
Do not store unused medicine for reuse. Unused medicine and waste material arising from this medicine must be disposed of in accordance with local regulations. This will help protect the environment.

6. Package contents and other information

What KIMMTRAK contains

• The active substance is tebentafusp. Each 0.5 mL vial of concentrate contains 100 micrograms of tebentafusp.
• The other components are monohydrate citric acid (E330), monosodium phosphate dihydrate (E339), mannitol (E421), trehalose, polysorbate 20 (E432), and water for injections (see section 2).

Description of the appearance of KIMMTRAK and package contents
KIMMTRAK concentrate for solution for infusion (sterile concentrate) is a clear, colourless to slightly yellowish solution in a single-dose glass vial.
The pack contains 1 vial 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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder in the following countries:
BE, BG, CZ, DE, DK, EE, IE, FR, HR, IT, CY, EL:
LV, LT, LU, HU, MT, NL, AT, PL, PT, RO, SI,
SK, FI, SE, UK-NI: Medison Pharma Greece Μονοπροσωπη
Ανωνυμη Εταιρεία
Immunocore Ireland Limited Tel: +30 210 0100 188
Ирландия/Irsko/Irland/Ιρλανδία/Iirimaa/Irlanti/Irl
ande/Irska/Írország/Írland/Irlanda/Airija/Īrija/L-
Irlanda/Ierland/Irlandia/Írsko/Irska
Tél/Tel/Tel./Teл./Tlf/Τηλ/Sími/Puh: +3531 691

More detailed information on this medicinal product 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.

The following information is intended exclusively for healthcare professionals:

Important: Before use, consult the Summary of Product Characteristics (SmPC).
General precautions
The infusion solution must be prepared by a healthcare professional using an appropriate aseptic technique throughout the entire handling process of this medicinal product.
Do not use closed-system transfer devices (CSTDs) for the preparation of doses of KIMMTRAK infusion solution.
Parenteral medicines and infusion bags should be visually inspected before administration for the presence of particulate matter or discoloration, wherever the solution and container permit.

Preparation
KIMMTRAK must be diluted prior to intravenous administration. Each vial of KIMMTRAK is for single use only. DO NOT shake the KIMMTRAK vial.
Before preparing KIMMTRAK for administration, ensure the following materials are available:

• Sterile 1 mL syringes with 2-decimal-place graduations;
• Sterile needles;
• Human albumin at locally available concentrations, for example but not limited to, 4% (40 g/L), 5% (50 g/L), 20% (200 g/L), 25% (250 g/L);
• A 100 mL infusion bag containing sodium chloride 9 mg/mL (0.9%) injection solution: the infusion bag must be composed of polyolefins (PO) [such as polyethylene (PE) and polypropylene (PP)] or polyvinyl chloride (PVC);
• A sterile, pyrogen-free infusion set with an in-line 0.2 micron low-protein-binding filter for administration of the final infusion bag.

Dilution and administration
The preparation of the final KIMMTRAK dose requires a two-step process.
Step 1. Preparation of the infusion bag
Using an aseptic technique, prepare the infusion bag as illustrated below:
a. Using a 1 mL syringe and a sterile needle, withdraw the calculated volume of human albumin into the syringe (see Table 1 below) and add it to the 100 mL infusion bag containing sodium chloride 9 mg/mL (0.9%) injection solution, to achieve a final human albumin concentration between 225 mcg/mL and 275 mcg/mL.
Table 1. Examples of possible withdrawal volumes for different human albumin concentrations
human

b. Gently and homogeneously mix the diluted solution by completing the following steps.
i. Invert the infusion bag so that the inlet port is positioned at the top of the bag, and gently tap the side of the tube connected to the port to ensure any residual solution is released into the bulk solution.
ii. Mix by gently rotating the bag 360 degrees lengthwise from the inverted position at least five times. DO NOT shake the infusion bag.
iii. Repeat steps (i) and (ii) three more times.
Step 2. Preparation of the KIMMTRAK infusion solution
c. Using a 1 mL syringe and a sterile needle, withdraw the volume of KIMMTRAK 100 micrograms/0.5 mL required to achieve the prescribed dose (as shown in Table 2 below), and add it to the previously prepared 100 mL infusion bag containing sodium chloride 9 mg/mL (0.9%) injection solution and human albumin.
d. DO NOT rinse the needle or syringe before transfer. Dispose of the vial containing any unused portion of KIMMTRAK according to local regulations. Do not prepare more than one dose from the same vial.
Table 2. Volumes of KIMMTRAK required to be added to the infusion bag

e. Mix the infusion bag, following the same procedure described in step 1b.
Administration

• KIMMTRAK must be administered exclusively by intravenous infusion.
• Begin the infusion immediately, lasting between 15 and 20 minutes, through a dedicated intravenous line, using a sterile, pyrogen-free infusion set with a 0.2 micron in-line low protein-binding filter. Administer the entire contents of the KIMMTRAK infusion bag to the patient.
• At the end of the KIMMTRAK infusion, flush the infusion line with an adequate volume of sterile 9 mg/mL (0.9%) sodium chloride injection solution to ensure that the entire contents of the infusion bag have been delivered. KIMMTRAK must not be administered by rapid intravenous injection or as a bolus. Do not mix KIMMTRAK with other medicinal products, nor administer other medicinal products 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, including the duration of the infusion. During these 4 hours, the KIMMTRAK infusion bag must be kept at a temperature below 30 °C.
• If not used immediately, the KIMMTRAK infusion bag must be stored refrigerated at a temperature between 2°C and 8°C for up to 24 hours from the time of preparation, including the time required 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. Discard any unused KIMMTRAK solution after the recommended storage time has elapsed.

ANNEX IV
SCIENTIFIC CONCLUSIONS AND REASONS FOR THE CHANGE IN THE TERMS OF THE MARKETING AUTHORISATION(S)
Scientific conclusions
Taking into account the evaluation by the Pharmacovigilance Risk Assessment Committee (PRAC) of the Periodic Safety Update Report(s) (PSUR) for tebentafusp, the scientific conclusions of the PRAC are as follows:
In light of the available data on serious complications of cytokine release syndrome emerging from spontaneous reports and the literature, the PRAC concluded that the product information for medicinal products containing tebentafusp should be amended accordingly.
Having reviewed the PRAC's recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and reasoning of the recommendation.
Reasons for the change in the terms of the marketing authorisation(s)
Based on the scientific conclusions for tebentafusp, the CHMP considers that the benefit-risk balance of the medicinal product(s) containing tebentafusp remains unchanged, subject to the proposed amendments to the product information.
The CHMP recommends a change to the terms of the marketing authorisation(s).