Loqtorzi 240 mg concentrate for solution for infusion

Patient Information Leaflet

Introduction

Package leaflet: Information for the patient

LOQTORZI 240 mg concentrate for solution for infusion

toripalimab

This medicinal product is subject to additional monitoring, which will enable quicker identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is included at the end of section 4.

Read this entire leaflet carefully before you start receiving this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• It is important that you carry the patient information card with you during treatment.
• If you have any questions, consult your doctor.
• If you experience any side effects, consult your doctor, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What LOQTORZI is and what it is used for

LOQTORZI contains the active substance toripalimab, which is a monoclonal antibody, a type of protein designed to recognise a specific substance in the body and bind to it.

LOQTORZI is used in adults to treat:

• a type of head and neck cancer called nasopharyngeal cancer that starts in the upper part of the throat behind the nose and near the base of the skull. It is used when the cancer has spread to other parts of the body, or has come back after previous treatment and cannot be removed by surgery.
• a type of oesophageal cancer called oesophageal squamous cell carcinoma. It is used when the cancer cannot be removed by surgery, has come back after previous treatment, or has spread to other parts of the body.

LOQTORZI is administered in combination with other anticancer medicines. It is important that you also read the package leaflets for these medicines. If you have any questions about LOQTORZI or these other medicines, ask your doctor.

The active substance in LOQTORZI, toripalimab, works by binding to a specific protein called programmed death receptor-1 (PD-1). The PD-1 protein can stop the activity of T lymphocytes (a type of white blood cell that is part of the immune system, the body's natural defences), thereby preventing the immune system from fighting cancer. By binding to the PD-1 protein, toripalimab blocks its action and prevents it from deactivating T lymphocytes. This helps increase their activity against cancer.

2. What you need to know before starting LOQTORZI

Do not receive LOQTORZI

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

Warnings and precautions

Talk to your doctor or nurse before receiving LOQTORZI:

• if you have an autoimmune disease (a condition in which the body attacks its own cells);
• if you have lung or breathing problems (called pneumonitis);
• if you have been told that your cancer has spread to the brain;
• if you have an active viral infection in the liver, such as hepatitis B (HBV) or hepatitis C (HCV);
• if you have active tuberculosis (TB);
• if you have human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS);
• if you have liver damage;
• if you have kidney damage;
• if you have received a solid organ transplant or a bone marrow transplant (stem cells) using donor stem cells (allogeneic transplant);
• if you are currently taking medicines that suppress your immune system, for example, corticosteroids such as prednisone.

LOQTORZI acts on your immune system. It may cause inflammation in parts of your body. The risk of these side effects may be higher if you already have an autoimmune disease (a condition in which the body attacks its own cells). You may also experience frequent flares of your autoimmune disease, which in most cases are mild.

If you are in any of the above situations (or are unsure), speak with your doctor before receiving LOQTORZI.

When receiving LOQTORZI, you may experience some serious side effects. These side effects can be potentially life-threatening and may occur at any time during treatment or even after treatment has ended. You may experience more than one side effect simultaneously.

If you experience any of the following conditions, call your doctor or seek immediate medical attention:

• inflammation of the lungs (pneumonitis), which may include symptoms such as shortness of breath, chest pain, or cough;
• inflammation of the large intestine (colitis), which may include symptoms such as diarrhea or more bowel movements than usual, tarry and sticky stools, or stools with blood or mucus, severe stomach pain, or a tender abdomen;
• inflammation of the liver (hepatitis), which may include symptoms such as nausea or vomiting, loss of appetite, pain in the right side of the stomach, yellowing of the skin or whites of the eyes, dark or cloudy urine, or bleeding or bruising more easily than normal;
• inflammation of hormone-secreting glands (especially the thyroid gland, pituitary gland, and adrenal glands), which may include symptoms such as rapid heartbeat, weight loss, increased sweating, weight gain, hair loss, feeling cold, constipation, deeper voice, muscle aches, dizziness or fainting, persistent headaches, or atypical headaches;
• type 1 diabetes, including diabetic ketoacidosis (acid in the blood caused by diabetes), which may include symptoms such as increased hunger or thirst, frequent urination, weight loss, feeling tired or nauseous, stomach pain, deep and rapid breathing, confusion, unusual drowsiness, sweet-smelling breath, or urine or sweat with a different odor;
• inflammation of the kidneys (nephritis), which may include symptoms such as changes in the amount or color of urine;
• skin inflammation, which may include symptoms such as rash, itching, blistering, peeling or sores on the skin, or ulcers in the mouth or mucous membranes of the nose, throat, or genital area;
• inflammation of the heart muscle (myocarditis), which may include symptoms such as shortness of breath, irregular heartbeat, feeling tired, or chest pain;
• inflammation of the muscles (myositis), which may include symptoms such as muscle pain or weakness;
• inflammation of the uvea, the layer beneath the white of the eye (uveitis), which may include changes in vision;
• inflammation of the pancreas (pancreatitis), which may include symptoms such as abdominal pain, nausea, and vomiting;
• inflammation of the bladder (cystitis), which may include symptoms such as pain when urinating and blood in the urine;
• inflammation of the joints (arthritis/arthralgia), which may include symptoms such as painful, red, or swollen joints or permanent joint damage;
• infusion-related reactions, which may include symptoms such as fever, chills, itching or rash, nausea, and low blood pressure;
• problems in other parts of the body (see section 4 “Possible side effects”).

Your doctor may give you other medicines to prevent more serious complications and relieve your symptoms, delay the next dose of LOQTORZI, or stop your treatment with this medicine. Note that sometimes these signs and symptoms may appear later, weeks or even months after your last dose. Before treatment, your doctor will assess your overall health. Blood tests will also be performed during treatment.

Use of LOQTORZI may lead to rejection of solid organ transplants (such as kidney, lung, heart, or liver transplants) in patients who have received such transplants, as well as complications such as graft-versus-host disease (GVHD) in individuals who have received an allogeneic stem cell transplant (using donor stem cells). These complications can be severe and may result in death. They may occur if you have received such a transplant in the past or if you receive one in the future. Your doctor will monitor you for signs and symptoms of these complications, such as skin rash, liver inflammation, abdominal pain, or diarrhea.

Children and adolescents

LOQTORZI must not be used in children and adolescents under 18 years of age, as it has not been studied in patients under this age.

Other medicines and LOQTORZI

Inform your doctor or nurse:

• if you are taking medicines that suppress your immune system, such as corticosteroids (e.g., prednisone). These medicines may interfere with the effect of LOQTORZI. However, during treatment with LOQTORZI, your doctor may prescribe corticosteroids to relieve side effects caused by this medicine. Corticosteroids may also be given before LOQTORZI in combination with chemotherapy to prevent or treat nausea, vomiting, and other chemotherapy-related side effects.
• if you are taking, have recently taken, or might need to take any other medicine. Do not take any other medicine during your treatment without first discussing it with your doctor.

Pregnancy

• You must not receive LOQTORZI if you are pregnant, unless your doctor specifically recommends it.
• If you are pregnant, think you might be pregnant, or plan to become pregnant, consult your doctor before using this medicine.
• LOQTORZI may cause harm or death to the unborn baby.
• If you are a woman of childbearing potential, you must use an effective method of contraception during treatment with LOQTORZI and for at least 4 months after your last dose.

Breastfeeding

• If you are breastfeeding, consult your doctor before using this medicine.
• You must not breastfeed during treatment and for at least 4 months after the last dose of LOQTORZI.
• It is unknown whether LOQTORZI is excreted in human breast milk.

Driving and using machines

LOQTORZI may have a minor effect on the ability to drive and use machines, as dizziness or fatigue are possible side effects. Do not drive or operate machinery unless you are certain you feel well.

LOQTORZI contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially "sodium-free." However, before LOQTORZI is administered, this medicine is mixed with a solution containing sodium. Talk to your doctor if you are on a low-salt diet.

3. How LOQTORZI is given

LOQTORZI will be administered to you in a hospital or clinic under the supervision of a doctor experienced in cancer treatment.

The recommended dose is 240 mg every 3 weeks. Your doctor will give it to you as an intravenous infusion (drip). The first infusion will last approximately 60 minutes. For subsequent doses, the duration may be reduced to about 30 minutes.

Your doctor will decide how many treatments you will need.

LOQTORZI is given in combination with other cancer medicines. LOQTORZI will be administered first, followed by the other medicines.

If you miss an appointment to receive LOQTORZI

Contact your doctor or hospital immediately to reschedule your appointment. It is very important not to miss any dose of this medicine.

If you interrupt treatment with LOQTORZI

If you interrupt your treatment, you may stop experiencing the effect of this medicine. Do not interrupt treatment with LOQTORZI without first consulting your doctor.

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

Patient information card

Important information from this leaflet can be found on the patient information card provided by your doctor. It is important that you keep this patient information card and show it to your partner or caregivers.

4. Possible adverse effects

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

Below is a list of serious adverse effects by frequency, which may lead to hospitalization or death.

Uncommon (may affect up to 1 in 100 people)

• inflammation of the lungs (pneumonitis)
• skin inflammation (immune-mediated skin reactions)
• liver inflammation (hepatitis)
• inflammation of the heart muscle (myocarditis)
• muscle inflammation (myositis)
• inflammation of the large intestine (colitis)
• adrenal gland inflammation (adrenal insufficiency)
• kidney inflammation (nephritis)
• decreased platelet count (immune thrombocytopenia)
• thyroid gland inflammation (hyperthyroidism, thyroiditis)
• thyroid inflammation (hypothyroidism)
• inflammation of insulin-producing cells (diabetes mellitus, hyperglycemia)
• pituitary gland inflammation (hypophysitis)
• infusion-related reactions

Rare (may affect up to 1 in 1,000 people)

• pancreas inflammation (pancreatitis)
• bladder inflammation (cystitis)
• joint inflammation (arthritis, arthralgia)

Problems in other parts of the body, other immune-mediated adverse effects (frequency cannot be estimated from available data on toripalimab, but have been reported with this class of medicines)

• brain inflammation (encephalitis), which may include symptoms such as confusion, fever, memory problems, or seizures
• myasthenic syndrome, a condition in which muscles become weak and tire easily
• nerve inflammation, including Guillain-Barré syndrome: symptoms may include muscle weakness in arms and legs, or facial muscles, double vision, and tingling in hands and feet
• rhabdomyolysis, with symptoms such as muscle and joint stiffness and muscle spasms
• transplant organ rejection
• uvea inflammation (uveitis)

If you experience any of these serious adverse effects, seek urgent medical attention or contact your doctor immediately.

The following adverse effects have been reported in clinical studies with toripalimab:

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

• decreased appetite
• weight loss
• fatigue (feeling tired)
• pyrexia (fever)
• cough
• abdominal pain (stomach pain)
• pain
• nausea
• vomiting
• diarrhea, colitis (inflammation of the large intestine)
• constipation
• neuropathy (nerve damage)
• anemia (low red blood cell levels)
• thrombocytopenia (low platelet levels in blood, which are components that help blood clotting)
• leukopenia (low white blood cell levels)
• neutropenia (low neutrophil levels, a type of white blood cell)
• upper respiratory tract infection (nose and throat infection)
• hyponatremia (low sodium levels in blood)
• hypoproteinemia (low protein levels in blood)
• hypokalemia (low potassium levels in blood, which may cause muscle weakness, cramps, tingling, and irregular heartbeat)
• hyperglycemia (high blood glucose levels)
• hyperuricemia (high levels of uric acid, a metabolic byproduct, in blood)
• hyperbilirubinemia (high bilirubin levels, a breakdown product of red blood cells, in blood, which may cause yellowing of the skin and eyes)
• proteinuria (excess protein in urine)
• hematuria (blood in urine)
• skin rash with inflammation, itching, blistering, peeling or sores, acne-like skin condition
• pruritus (itching)
• pain
• musculoskeletal pain (muscle and bone pain)
• hypothyroidism (underactive thyroid gland, with symptoms of tiredness, weight gain, and changes in skin and hair)
• arrhythmia (abnormal or irregular heartbeat)
• abnormal liver function test results
• abnormal thyroid function test results
• abnormal blood lipid level test results
• abnormal urine test results

Common (may affect up to 1 in 10 people)

• vomiting; flatulence and abdominal distension; stomach acid reflux; blood in stool
• decreased intestinal content flow or intestinal obstruction
• mouth sores or burning sensation in mouth, gums, throat, or esophagus; dry mouth; toothache
• overactive thyroid gland
• chills, flu-like illness
• pain (in muscles, bones, lymph nodes, and chest)
• eye disorder (dry or itchy eyes, cataracts)
• kidney damage
• shortness of breath; lung inflammation, fluid around the lungs; nosebleeds, coughing up blood, congestion or irritation of upper airways
• decreased platelet count (bruising or bleeding more easily)
• sleep problems; mood changes
• night sweats; increased sweating
• nerve inflammation causing numbness, weakness, tingling or burning; headache; dizziness
• lung infection, urinary tract infection, infection, ear infections, fungal mouth infection, herpes virus infection
• skin color changes in patches (including loss of pigmentation, vitiligo), hair loss, dry skin, hair color changes, increased sensitivity to sunlight, skin peeling or sores
• muscle weakness
• liver inflammation
• high or low blood pressure; blood clots; pain caused by cancer
• ear disorder, ear pain, ringing in ears; hearing loss; blurred vision
• lung infection, upper respiratory tract infection, urinary tract infection

Uncommon (may affect up to 1 in 100 people)

• stomach inflammation
• pancreas inflammation
• type 1 diabetes, including diabetic ketoacidosis
• muscle pain
• temperature intolerance, thirst
• breathing difficulties, wheezing, hoarseness
• sinus congestion, speech joint abnormalities
• reactions related to drug infusion
• change in taste sensation; drowsiness; speech disorder
• conjunctivitis, gingivitis, skin and subcutaneous tissue infections
• joint inflammation; disc herniation; muscle spasms
• liver pain, gallbladder inflammation
• decreased secretion of hormones produced by adrenal glands; pituitary gland inflammation, a gland located at the base of the brain
• thyroid gland inflammation
• fluid accumulation around the heart; heart muscle inflammation; heart muscle damage
• tumor hemorrhage, tumor rupture
• genital edema, scrotal edema
• eye inflammation (causing eye pain and redness), problems with coordinated eye movement; optic nerve inflammation
• allergic reaction

Rare (may affect up to 1 in 1,000 people)

• gas in the intestinal wall, loss of sensation in the mouth, swelling or color change of the tongue
• inflammation of the layers covering the lungs; increased sputum production
• vocal cord thickening
• diverticulitis
• skin inflammation (thickened, sometimes scaly skin; chronic itching or scaling; skin pain)
• muscle inflammation which may include muscle pain or weakness (myositis), and may be associated with a rash (dermatomyositis)
• subcutaneous fat inflammation, skin bruising
• overactivity of the parathyroid gland; underactivity of the pituitary gland
• limb paralysis, attention disturbance
• aortic aneurysm
• menstrual abnormalities
• vaginal discharge, or itching or pain in the skin of the outer vagina
• hearing loss; sensation of loss of balance
• eyelid swelling and itching; hypermetropia (blurred near vision)
• infection

Consult your doctor if you experience any of the adverse effects listed above.

Changes in test results

LOQTORZI alone or in combination may cause changes in test results performed by your doctor, such as:

• abnormalities in liver function tests (such as elevated blood levels of liver enzymes aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, or alkaline phosphatase)
• abnormalities in kidney function tests (such as elevated blood levels of creatinine and other waste products, uric acid, and urea; increased number of cells or amount of protein in urine; abnormal levels of waste products in urine)
• elevated levels of the enzyme that breaks down fats and the enzyme that breaks down starch
• decreased blood levels of potassium, calcium, sodium, magnesium, chloride, phosphate, and proteins
• elevated blood levels of calcium, potassium, magnesium, sodium, or phosphate
• elevated levels of muscle enzymes in blood
• abnormalities in thyroid function tests; positive antithyroid antibody; weight gain
• abnormal blood levels of lipids and proteins
• changes in acid-base balance in blood
• decreased levels of more than one type of blood cell (white blood cells, red blood cells, platelets)
• elevated white blood cell and neutrophil counts; abnormal eosinophil count, elevated platelet count
• increased or decreased blood levels of hormones produced by endocrine glands
• abnormalities in cardiac tests

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of LOQTORZI

LOQTORZI will be administered to you in a hospital or clinic, and healthcare professionals will be responsible for its storage.

If you are given a box of LOQTORZI, it must be stored as follows:

• 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 vial label. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (between 2°C and 8°C). Do not freeze. Keep in the original packaging to protect from light.
• If the diluted solution is not used immediately, it may be stored at room temperature (up to 25°C) for a maximum of 8 hours, or at a temperature between 2°C and 8°C for a maximum of 24 hours from the time of dilution until the end of administration.
• Do not use this medicine if visible particles are present.
• Do not keep any leftover medicine for later use. Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations. This will help protect the environment.

6. Contents of the container and other information

Composition of LOQTORZI

• The active substance is toripalimab.

One 6 ml vial of concentrate for solution for infusion contains 240 mg of toripalimab.

Each millilitre of concentrate for solution for infusion contains 40 mg of toripalimab.

• The other components are monohydrate citric acid, mannitol, polysorbate 80, sodium chloride, sodium citrate dihydrate (section 2 “LOQTORZI contains sodium”) and water for injections.

Appearance of the product and contents of the container

LOQTORZI is supplied as a solution ranging from transparent to slightly opalescent, from colourless to slightly yellowish, essentially free from visible particles.

It is available in cartons containing one glass vial with 6 ml of concentrate for solution for infusion.

Marketing Authorization Holder

Topalliance Biosciences Europe Limited

Ground Floor

Two Dockland Central

Guild Street

I.f.s.c.

Dublin 1

Co. Dublin

D01 K2C5

Ireland

Manufacturer

Eurofins PHAST GmbH

Kardinal-Wendel-Strasse 16

Homburg

Saarland

66424

Germany

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent revision of this leaflet:

Other sources of information

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