Jemperli

Package leaflet: Information for the patient

JEMPERLI 500 mg concentrate for solution for infusion

dostarlimab
This medicinal product is subject to additional monitoring. This will allow for 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 taking this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• Your doctor will provide you with a Patient Card. Make sure to carry this card with you at all times while you are receiving treatment with JEMPERLI.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What JEMPERLI is and what it is used for

JEMPERLI contains the active substance dostarlimab, which is a monoclonal antibody, a type of
protein designed to recognise a specific target substance in the body and bind to it.
JEMPERLI works by helping the immune system to fight cancer.
JEMPERLI is used in adults for the treatment of a type of cancer called endometrial cancer
(cancer of the lining of the uterus). It is given when the cancer is diagnosed for the first time, has spread or cannot be surgically removed, or is progressing during or after prior treatment.
JEMPERLI may be administered in combination with other anti-cancer medicines. It is important
that you also read the package leaflets of any other anti-cancer medicines you may be taking.
If you have any questions about these medicines, ask your doctor.

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

Do not receive JEMPERLI:

• if you are allergic to dostarlimab or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or nurse before you are given JEMPERLI if you have:

• severe rash or skin peeling, blistering and/or mouth ulcers;
• immune system problems;
• lung or breathing problems;
• liver or kidney problems;
• any other medical condition.

Warnings and precautions – Special caution with JEMPERLI
This medicine can cause severe skin reactions. Stop using JEMPERLI and contact your doctor
immediately if you notice any symptoms related to severe skin reactions described in section 4.
Symptoms to watch for
JEMPERLI may cause serious side effects, which can sometimes become potentially life-threatening
and may lead to death. These side effects may occur at any time during treatment, or even after
treatment has ended. You may experience several side effects at the same time.
Pay attention to possible symptoms so that your doctor can provide treatment for side effects if
necessary.
Read the information provided in section 4 under “Symptoms of serious side effects”. If you
have any doubts or concerns, talk to your doctor or nurse.
Children and adolescents
JEMPERLI must not be used in children and adolescents under 18 years of age.
Other medicines and JEMPERLI
Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
Some medicines may interfere with the effects of JEMPERLI:

• medicines that weaken the immune system – for example, corticosteroids such as prednisone. Tell your doctor if you are taking any of these medicines.

However, once you have started treatment with JEMPERLI, your doctor may give you corticosteroids
to reduce any side effects.
Pregnancy

• Do not receive JEMPERLI if you are pregnant, unless specifically recommended by your doctor.
• If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, ask your doctor for advice before being given this medicine.
• JEMPERLI may cause harm or death to the unborn baby.
• If you are a woman of childbearing potential, you must use an effective contraceptive method during treatment with JEMPERLI and for at least 4 months after receiving the last dose.

Breast-feeding

• If you are breast-feeding, ask your doctor for advice before being given this medicine.
• You must not breast-feed during treatment and for at least 4 months after receiving the last dose of JEMPERLI.
• It is not known whether the active substance of JEMPERLI is excreted in breast milk.

Driving and using machines
It is unlikely that JEMPERLI will affect your ability to drive or use machines.
However, if you experience side effects that affect your concentration or reaction, take particular
care when driving or using machines.
JEMPERLI contains polysorbate 80
This medicine contains 2 mg of polysorbate 80 per dose. Polysorbates may cause allergic reactions.
Inform your doctor if you have known allergies.
JEMPERLI contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially “sodium-free”.
However, before administration, JEMPERLI is mixed with a solution that may contain sodium. Talk to your doctor if you are on a low-salt diet.

3. How JEMPERLI is administered

JEMPERLI will be administered to you at a hospital or clinic, under the supervision of a physician experienced in cancer treatment.

When JEMPERLI is given alone, the recommended dose of JEMPERLI is 500 mg every 3 weeks for 4 doses, followed by 1,000 mg every 6 weeks for all subsequent doses.

When JEMPERLI is given in combination with carboplatin and paclitaxel, the recommended dose of JEMPERLI is 500 mg every 3 weeks for 6 doses, followed by 1,000 mg every 6 weeks for all subsequent doses.

Your doctor will administer JEMPERLI to you as an intravenous infusion ( intravenous infusion ) lasting approximately 30 minutes.

Your doctor will decide how many treatments you need.

If you miss an appointment for JEMPERLI administration
Contact your doctor or hospital immediately to reschedule the infusion.
It is extremely important that you do not miss any doses of the medicine.

If you interrupt JEMPERLI administration
Interrupting treatment may reduce the effectiveness of the medicine. Do not stop treatment with JEMPERLI without first discussing it with your doctor.

Patient card
You can find the important information from this leaflet in the patient card provided by your doctor. It is important that you keep this patient card and show it to your partner or caregiver.

If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some of these side effects can be serious, and it is important that you are aware of the symptoms you should pay attention to.
Symptoms of serious side effects
JEMPERLI may cause serious side effects. If you develop any symptoms, you must inform your doctor or
nurse as soon as possible. Your doctor may give you other medicines to reduce the symptoms and prevent more serious complications. Your doctor may also decide to skip a dose of JEMPERLI or to stop treatment completely.

Infusion reactions
After an infusion, some people may experience reactions similar to those of an allergic reaction. These
usually occur within minutes or hours, but may appear up to 24 hours after treatment.
Symptoms include:

• shortness of breath or wheezing;
• itching or skin rash;
• flushing;
• dizziness;
• chills or shaking;
• fever;
• drop in blood pressure (feeling faint).

Rejection of solid organ transplant and other complications, including graft-versus-host disease (GvHD), in patients who have received a bone marrow transplant (stem cells) using donor stem cells (allogeneic). These complications can be serious and may lead to death. These complications may occur whether the transplant was performed before or after treatment with JEMPERLI. Your doctor will monitor you for these complications.
Contact your doctor immediately if you think you are having a reaction.

The following adverse reactions have been reported with JEMPERLI as monotherapy.
Very common adverse reactions (may affect more than 1 in 10 people):

• reduction in red blood cell count (anaemia);
• reduced thyroid activity;
• diarrhoea; feeling unwell (nausea); feeling unwell (vomiting);
• redness of the skin or skin rash; blistering of the skin or mucous membranes; skin itching;
• joint pain;
• high temperature, fever;
• increased liver enzyme levels in the blood. Please refer to the table above for symptoms of possible serious adverse reactions.

Common adverse reactions (may affect up to 1 in 10 people):

• overactivity of the thyroid gland;
• reduced secretion of adrenal hormones (adrenal insufficiency);
• inflammation of the lungs;
• inflammation of the lining of the intestine (colon);
• inflammation of the pancreas;
• inflammation of the stomach;
• inflammation of the liver;
• muscle pain;
• chills;
• infusion reaction;
• hypersensitivity reaction to infusion. Please refer to the table above for symptoms of possible serious adverse reactions.

Uncommon adverse reactions (may affect up to 1 in 100 people):

• inflammation of the brain;
• destruction of red blood cells (autoimmune haemolytic anaemia);
• inflammation of the pituitary gland, a gland located at the base of the brain;
• inflammation of the thyroid gland;
• type 1 diabetes or diabetes complications (diabetic ketoacidosis);
• inflammation of the oesophagus;
• inflammation of the skin (pemphigoid, Stevens-Johnson syndrome);
• a condition in which muscles become weak and tire quickly (myasthenia gravis);
• joint inflammation;
• muscle inflammation;
• inflammation of the eye – iris (coloured part) and ciliary body (area around the iris);
• inflammation of the kidneys. Please refer to the table above for symptoms of possible serious adverse reactions.

Other reported adverse reactions (frequency not known):

• coeliac disease (characterised by symptoms such as abdominal pain, diarrhoea and abdominal swelling after consuming foods containing gluten);
• absence or reduced production of digestive enzymes by the pancreas (pancreatic exocrine insufficiency).

The following adverse reactions have been reported with JEMPERLI when administered in
combination with carboplatin and paclitaxel.
Very common adverse reactions (may affect more than 1 in 10 people):

• underactive thyroid gland;
• skin rash;
• dry skin;
• high temperature; fever;
• increased liver enzyme levels in the blood. Please refer to the table above for symptoms of possible serious adverse reactions.

Common adverse reactions (may affect up to 1 in 10 people):

• overactive thyroid gland;
• inflammation of the lungs;
• inflammation of the lining of the intestine (colon);
• inflammation of the pancreas. Please refer to the table above for symptoms of possible serious adverse reactions.

Uncommon adverse reactions (may affect up to 1 in 100 people):

• inflammation of the thyroid gland;
• reduced secretion of adrenal hormones (adrenal insufficiency);
• type I diabetes;
• a condition in which muscles become weak and tire quickly (myasthenic syndrome);
• inflammation of the nerves which may cause pain, numbness, muscle weakness and difficulty walking (Guillain-Barré syndrome);
• inflammation of the heart muscle;
• inflammation of the stomach;
• inflammation of blood vessels in the gastrointestinal tract, stomach or intestine;
• inflammation of the eye;
• joint inflammation;
• muscle inflammation;
• systemic inflammation. Please refer to the table above for symptoms of possible serious adverse reactions.

Other reported adverse reactions (frequency not known):

• coeliac disease (characterised by symptoms such as abdominal pain, diarrhoea and abdominal swelling after consuming foods containing gluten);
• absence or reduced production of digestive enzymes by the pancreas (pancreatic exocrine insufficiency).

Contact your doctor or nurse as soon as possible if you experience any of these symptoms.
Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet, talk to your doctor or nurse. You can also report adverse reactions directly via the national reporting system detailed in Annex V. By reporting adverse reactions, you can help provide more information on the safety of this medicine.

5. How to store JEMPERLI

JEMPERLI will be administered to you in a hospital or clinic setting, and healthcare professionals will be responsible for its storage.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and on the label of the vial after "Exp.". The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C - 8 °C). Do not freeze. Keep in the original packaging to protect from light.
If not used immediately, the prepared infusion solution can be stored for up to 24 hours at a temperature between 2 °C and 8 °C or for 6 hours at room temperature (up to 25 °C), from the time of preparation/dilution until the end of administration.
Do not use this medicine if visible particles are present.
Do not store unused medicine for later use. Unused medicine and waste material derived 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 JEMPERLI contains

• The active substance is dostarlimab.
• One 10 mL vial of concentrate for solution for infusion (sterile concentrate) contains 500 mg of dostarlimab.
• Each mL of concentrate for solution for infusion contains 50 mg of dostarlimab.
• The other components are trisodium citrate dihydrate (E331), citric acid monohydrate (E330), L-arginine hydrochloride, sodium chloride, polysorbate 80 (E433) and water for injections (see section 2).

Description of the appearance of JEMPERLI and contents of the pack
JEMPERLI is a solution ranging from clear to slightly opalescent, from colourless to yellow, essentially free from visible particles.
It is available in cartons containing one glass vial.

Marketing Authorisation Holder
GlaxoSmithKline Trading Services Limited
12 Riverwalk
Citywest Business Campus
Dublin 24
Ireland
D24 YK11

Manufacturer
GlaxoSmithKline Trading Services Ltd.
12 Riverwalk
Citywest Business Campus
Dublin 24
Ireland
GlaxoSmithKline Manufacturing S.p.A.
Strada Provinciale Asolana, 90
43056 San Polo di Torrile
Parma, Italy

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
GlaxoSmithKline Pharmaceuticals s.a./n.v. GlaxoSmithKline Trading Services Limited
Tél/Tel: + 32 (0) 10 85 52 00 Tel: + 370 80000334
[email protected]

България Luxembourg/Luxemburg
GlaxoSmithKline Trading Services Limited GlaxoSmithKline Pharmaceuticals s.a./n.v.
Teл.: + 359 80018205 Belgique/Belgien
Tél/Tel: + 32 (0) 10 85 52 00

Česká republika Magyarország
GlaxoSmithKline, s.r.o. GlaxoSmithKline Trading Services Limited
Tel: + 420 222 001 111 Tel.: + 36 80088309
[email protected]

Danmark Malta
GlaxoSmithKline Pharma A/S GlaxoSmithKline Trading Services Limited
Tlf.: + 45 36 35 91 00 Tel: + 356 80065004
[email protected]

Deutschland Nederland
GlaxoSmithKline GmbH & Co. KG GlaxoSmithKline BV
Tel.: + 49 (0)89 36044 8701 Tel: + 31 (0) 33 2081100
[email protected]

Eesti Norge
GlaxoSmithKline Trading Services Limited GlaxoSmithKline AS
Tel: + 372 8002640 Tlf: + 47 22 70 20 00

Ελλάδα Österreich
GlaxoSmithKline Μονοπρόσωπη A.E.B.E. GlaxoSmithKline Pharma GmbH
Τηλ: + 30 210 68 82 100 Tel: + 43 (0)1 97075 0
[email protected]

España Polska
GlaxoSmithKline, S.A. GSK Services Sp. z o.o.
Tel: + 34 900 202 700 Tel.: + 48 (0)22 576 9000
[email protected]

France Portugal
Laboratoire GlaxoSmithKline GlaxoSmithKline – Produtos Farmacêuticos, Lda.
Tél: + 33 (0)1 39 17 84 44 Tel: + 351 21 412 95 00
[email protected] [email protected]

Hrvatska România
GlaxoSmithKline Trading Services Limited GlaxoSmithKline Trading Services Limited
Tel: +385 800787089 Tel: + 40 800672524

Ireland Slovenija
GlaxoSmithKline (Ireland) Limited GlaxoSmithKline Trading Services Limited
Tel: + 353 (0)1 4955000 Tel: + 386 80688869

Ísland Slovenská republika
Vistor hf. GlaxoSmithKline Trading Services Limited
Sími: + 354 535 7000 Tel: + 421 800500589

Italia Suomi/Finland
GlaxoSmithKline S.p.A. GlaxoSmithKline Oy
Tel: + 39 (0)45 7741111 Puh/Tel: + 358 (0)10 30 30 30

Κύπρος Sverige
GlaxoSmithKline Trading Services Limited GlaxoSmithKline AB
Τηλ: + 357 80070017 Tel: + 46 (0)8 638 93 00
[email protected]

Latvija
GlaxoSmithKline Trading Services Limited
Tel: + 371 80205045

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.

The following information is intended exclusively for healthcare professionals:

Preparation/dilution, storage, and administration of the infusion solution

• Parenteral medicinal products should be inspected visually prior to administration for the presence of particulate matter and discoloration. JEMPERLI is a slightly opalescent solution, colorless to yellow. Discard the vial if visible particles are observed.
• JEMPERLI is compatible with intravenous infusion bags made of polyvinyl chloride (PVC) with or without di(2-ethylhexyl)phthalate (DEHP), ethylene vinyl acetate, polyethylene (PE), polypropylene (PP), or polyolefin blends (PP+PE), as well as with PP syringes.
• For the 500 mg dose, withdraw 10 mL of JEMPERLI from a vial and transfer it into an intravenous infusion bag containing either 9 mg/mL (0.9%) sodium chloride injection solution or 50 mg/mL (5%) glucose injection solution. The final concentration of the diluted solution must be between 2 mg/mL and 10 mg/mL. The total volume of the infusion solution must not exceed 250 mL. It may be necessary to remove a certain volume of diluent from the IV infusion bag before adding the corresponding volume of JEMPERLI.
• For example, when preparing a 500 mg dose in a 250 mL IV infusion bag of diluent, to achieve a concentration of 2 mg/mL, 10 mL of diluent should be removed from the 250 mL infusion bag. Then, 10 mL of JEMPERLI should be withdrawn from the vial and transferred into the infusion bag.
  • For the 1,000 mg dose, withdraw 10 mL of JEMPERLI from each of two vials (a total of 20 mL) and transfer them into an intravenous infusion bag containing either 9 mg/mL (0.9%) sodium chloride injection solution or 50 mg/mL (5%) glucose injection solution. The final concentration of the diluted solution must be between 4 mg/mL and 10 mg/mL. The total volume of the infusion solution must not exceed 250 mL. It may be necessary to remove a portion of the diluent from the IV infusion bag before adding the corresponding volume of JEMPERLI.
• For example, when preparing a 1,000 mg dose in a 250 mL IV infusion bag of diluent, to achieve a concentration of 4 mg/mL, 20 mL of diluent should be removed from the 250 mL infusion bag. Then, 10 mL of JEMPERLI should be withdrawn from each of two vials (for a total of 20 mL) and transferred into the infusion bag.
  • Mix the diluted solution by gently inverting the bag. Do not shake the infusion bag. Discard any unused portion remaining in the vial.
  • Store in the original packaging until time of preparation to protect the medicinal product from light. The prepared dose may be stored:
• at room temperature (up to 25 °C) for up to 6 hours from the time of dilution until the end of infusion;
• in the refrigerator (2 °C – 8 °C) for up to 24 hours from the time of dilution until the end of infusion. If refrigerated, allow the diluted solution to reach room temperature before administration.
  • JEMPERLI must be administered by a healthcare professional via a 30-minute intravenous infusion using an intravenous infusion pump.
  • Tubing should be made of PVC, platinum-cured silicone, or PP; connectors should be made of PVC or polycarbonate; and needles should be made of stainless steel.
  • An in-line filter made of polyethersulfone (PES) with a pore size of 0.2 or 0.22 micron must be used during administration of JEMPERLI.
  • JEMPERLI must not be administered by rapid intravenous injection or as a bolus injection.
  • Do not administer other medicinal products concomitantly through the same infusion line.

Any unused medicinal product and waste materials derived from this medicinal product must be disposed of in accordance with
local applicable regulations.
ANNEX IV
SCIENTIFIC CONCLUSIONS AND REASONS FOR THE VARIATION OF THE TERMS OF THE
MARKETING AUTHORISATION
Scientific conclusions
Taking into account the evaluation by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Report (PSUR) for dostarlimab, the scientific conclusions of the PRAC are as follows:
Considering the available data on Stevens-Johnson syndrome from spontaneous reports and a plausible mechanism of action, the PRAC Rapporteur considers that there is at least a reasonable possibility of a causal relationship between dostarlimab and Stevens-Johnson syndrome (SJS). The PRAC concluded that the product information for medicinal products containing dostarlimab should be amended accordingly.
Having reviewed the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and the rationale of the recommendation.
Reasons for the variation of the terms of the marketing authorisation
Based on the scientific conclusions regarding dostarlimab, the CHMP considers that the benefit-risk balance of the medicinal product containing dostarlimab remains unchanged, subject to the proposed amendments to the product information.
The CHMP recommends a variation to the terms of the marketing authorisation.