Prospect: information for the patient

Talvey 2 mg/ml injectable solution

Talvey 40 mg/ml injectable solution

talquetamab

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 prospectus carefully before starting to receive this medicine, as it contains important information for you.

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

6. Contents of the pack and additional information

Talvey is a cancer medication that contains the active ingredient «talquetamab». Talquetamab is an antibody, a type of protein that recognizes specific targets in the body and binds to them. It has been designed to bind to the GPRC5D protein (G protein-coupled receptor, family C, group 5 and member D), which is found in multiple myeloma cancer cells, and to the CD3 group (a protein on T cells, a type of white blood cell). T cells are part of the body's natural defenses and help protect it from infections.

They can also destroy cancer cells. When this medication binds to these cells, it links cancer cells and T cells. This stimulates T cells to destroy multiple myeloma cancer cells.

Talvey is used to treat adults with multiple myeloma, a bone marrow cancer.

It is used when patients have had at least three other types of treatment that either did not work or have stopped working.

Do not receive Talvey

• if you are allergic to talquetamab or any of the other components of this medication (listed in section 6).

Do not use Talvey if you experience the above. If you are unsure, speak with your doctor or nurse before receiving Talvey.

Warnings and precautions

Consult your doctor or nurse before starting to receive Talvey.

Severe side effects

There are severe side effects that may occur after starting to take Talvey. You must immediately inform your doctor or nurse if this occurs, as it may require immediate medical attention.

Immediately inform your doctor or nurse if you experience any of the following:

• signs of a condition known as "cytokine release syndrome" (CRS). CRS is a severe immune reaction that produces symptoms such as fever, low blood pressure, chills, difficulty breathing, fatigue, headache, tachycardia, and elevated liver enzymes in the blood.
• effects on the nervous system. Symptoms include feeling confused, disoriented, drowsy, lack of attention, slowness or difficulty thinking, altered thinking or decreased consciousness, confusion, difficulty speaking and understanding speech. Some of these may be signs of a severe immune reaction called "immune effector cell-associated neurotoxicity syndrome" (ICANS).
• problems in the mouth, such as loss of taste, dry mouth, difficulty swallowing, and inflammation of the mouth lining.
• skin problems such as rashes, redness, and nail problems.
• sensation of heat, fever, chills, sore throat, or mouth ulcers may be signs of an infection.

Talvey and vaccines

Speak with your doctor or nurse before receiving Talvey if you have recently been vaccinated or are to be vaccinated. Your immune system (the body's natural defenses) may not respond as well to vaccination while taking this medication.

You should not receive live vaccines, a specific type of vaccine, at least 4 weeks before starting your treatment with Talvey until at least 4 weeks after taking your last dose.

Tests and controls

Beforereceiving Talvey, your doctor will perform a blood test to see the levels of different blood cells and detect signs of infection. Infections will be treated before starting this medication.

Afterreceiving Talvey, your doctor will monitor you to detect side effects. They will also periodically check your blood counts, as the number of blood cells and other blood components may decrease when using this medication.

Children and adolescents

Talvey should not be used in children or adolescents under 18 years of age, as the medication has not been studied in this age group and its effects on them are unknown.

Other medications and Talvey

Inform your doctor or nurse if you are taking, have taken recently, or may need to take any other medication. This includes medications that can be obtained without a prescription and herbal remedies.

Pregnancy, contraception, and breastfeeding

Pregnancy and contraception

Talvey has the potential to be transmitted from the mother to the developing fetus. The effects of Talvey on the developing fetus are unknown, and it cannot be ruled out that there is a risk to newborns/breastfed infants.

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

If you become pregnant while on treatment with this medication, inform your doctor or nurse immediately.

If you can become pregnant, you must use an effective contraceptive method during treatment and for 3 months after stopping treatment with Talvey. Your doctor will check if you are pregnant before starting treatment.

If your partner becomes pregnant while you are taking this medication, inform your doctor immediately.

If you have received this medication during pregnancy, your newborn should not receive any live vaccines until they are at least 4 weeks old.

Breastfeeding

The effects of Talvey on breast milk are unknown. There may be a risk to newborns or breastfed infants. Consult your doctor before starting treatment with this medication. You and your doctor will decide if the benefits of breastfeeding outweigh the risks for your baby. If you and your doctor decide to stop taking this medication, do not breastfeed for 3 months after stopping treatment.

Fertility

There are no data on the effect of talquetamab on fertility. Talquetamab has not been evaluated for its effects on male and female fertility in animal studies.

Driving and operating machinery

Some people may feel tired, dizzy, or confused when taking Talvey. Do not drive, use tools, or operate machinery from the time you receive your first dose until at least 48 hours after receiving your first dose of Talvey, or as instructed by your doctor.

Talvey contains sodium

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

Amount Administered

Talvey will be administered under the supervision of an experienced doctor who treats patients with multiple myeloma. Your doctor will determine how much Talvey you receive. The Talvey dose will depend on your body weight.

Talvey is administered once a week or once every 2 weeks, depending on the dose, as indicated below:

0.4 mg/kg once a week:

• In the first dose, you will receive 0.01 mg per kilogram of body weight.
• In the second dose, which will be administered 2-4 days later, you will receive 0.06 mg per kilogram of body weight.
• In the third dose, you will receive a "treatment dose" of 0.4 mg per kilogram of body weight 2-4 days after the second dose.
• After the third dose, you will then receive a "treatment dose" once a week from then on.
• Treatment will continue as long as you benefit from using Talvey.

Your doctor will monitor you for adverse effects after each of your first three doses.

This will be done for 2 days after each dose. You must remain near a medical facility after each of the first three doses in case you experience adverse effects.

If you experience adverse effects after any of your first two doses, your doctor may decide to wait up to 7 days before administering the next dose.

0.8 mg/kg once every 2 weeks:

• In the first dose, you will receive 0.01 mg per kilogram of body weight.
• In the second dose, which will be administered 2-4 days later, you will receive 0.06 mg per kilogram of body weight.
• In the third dose, which will be administered 2-4 days later, you will receive 0.4 mg per kilogram of body weight.
• In the fourth dose, you will then receive a "treatment dose" of 0.8 mg per kilogram of body weight 2-4 days after the third dose.
• After the fourth dose, you will then receive a "treatment dose" once every 2 weeks from then on.
• Treatment will continue as long as you continue to benefit from using Talvey.

Your doctor will monitor your adverse effects after each of the first four doses. This will be done for 2 days after each dose. You must remain near a medical facility after receiving each of the first four doses in case you experience adverse effects.

If you experience adverse effects after any of your first three doses, your doctor may decide to wait up to 7 days before administering the next dose.

The decision to use 0.4 mg/kg once a week or 0.8 mg/kg every 2 weeks will be made in consultation with your doctor.

How the Medication is Administered

Talvey will be administered by a doctor or nurse as an injection under your skin (subcutaneous injection). It is administered in the abdominal area or in the thigh.

Other Medications Administered During Treatment with Talvey

Before your first three doses (if you are receiving 0.4 mg/kg of body weight) or your first four doses (if you are receiving 0.8 mg/kg of body weight) of Talvey, you will be given medications to help reduce the likelihood of adverse effects. These may include:

• medications to reduce an allergic reaction (antihistamines)
• medications to reduce inflammation (corticosteroids)
• medications to reduce fever (such as paracetamol)

It is possible that you will also be given these medications when you receive subsequent doses of Talvey, depending on your symptoms.

You may also be given additional medications based on your symptoms or medical history.

If You Receive More Talvey Than You Should

This medication will be administered by your doctor or nurse. If you receive an excessive amount (an overdose), your doctor will examine you to see if you experience any adverse effects.

If You Miss Your Appointment for Talvey Administration

It is very important to attend all appointments so that treatment can be effective. If you miss an appointment, reschedule as soon as possible.

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

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

Severe side effects

Seek immediate medical attention if you experience any of the following severe side effects, which could be serious or even life-threatening.

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

• Immune effector cell-associated neurotoxicity syndrome (ICANS), a severe immunological reaction that can affect your nervous system. Some symptoms are:

• feeling of confusion
• feeling less alert or conscious
• disorientation
• drowsiness
• little energy
• slowness and difficulty thinking.

• Cytokine release syndrome (CRS), a severe immune reaction. CRS can cause symptoms such as:

• fever
• low blood pressure
• chills
• low oxygen levels in the blood
• headache
• tachycardia
• increased levels of liver enzymes in the blood

• Low levels of neutrophils (neutropenia), a type of white blood cell that helps fight infections
• Reduced number of 'platelets' in the blood (thrombocytopenia), which helps with blood clotting;

Immediately report to your doctor if you experience any of the above-mentioned severe side effects.

Other side effects

The following are other side effects. If you experience any of these side effects, report to your doctor or nurse.

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

• Nail problems
• Muscle and bone pain (musculoskeletal pain)
• Reduced number of red blood cells (anemia)
• Feeling tired
• Chills
• Weight loss
• Abnormally dry skin, such as the mouth and eyes (xerosis)
• Reduced number of lymphocytes (lymphopenia), a type of white blood cell
• Difficulty producing or controlling movement (motor dysfunction)
• Feeling dizzy
• Nerve damage that can cause tingling, numbness, pain, or loss of sensation (sensory neuropathy)
• Damage or disease affecting brain function (encephalopathy)
• Diarrhea
• Nausea
• Constipation
• Stomach pain
• Vomiting
• Upper respiratory tract infection, including nasal, sinus, or throat infection
• Itching (pruritus)
• Decreased appetite
• Pain
• Reduced number of white blood cells (leukopenia)
• Low levels of 'potassium' in the blood (hypokalemia)
• Low levels of 'phosphate' in the blood (hypophosphatemia)
• Low levels of 'magnesium' in the blood (hypermagnesemia)
• Low level of immunoglobulins, a type of antibody in the blood (hypogammaglobulinemia), which can increase the risk of infections
• Swelling caused by the accumulation of fluid in the body (edema)

• Irritation or pain at the injection site
• Increased liver enzymes in the blood
• COVID-19 infection
• Blood tests may show that the blood takes longer to clot (decreased fibrinogen, elevated INR, and prolonged TTPa)
• Bacterial infection
• Mouth pain
• Fungal infection
• Fever (pyrexia)
• Headache
• Difficulty breathing (dyspnea)
• Cough
• Problems with the mouth and swallowing, such as changes in taste (dysgeusia), dry mouth, difficulty swallowing (dysphagia), and inflammation of the mouth lining (stomatitis)
• Skin problems, including skin rash

Common (may affect up to 1 in 10 people)

• Hair loss
• Bleeding, which can be severe (hemorrhages)
• Pneumonia
• Viral infection
• Septicemia (blood infection)
• Low count of a type of white blood cell (neutrophils), with fever

Reporting side effects

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

Your doctor will store Talvey at the hospital or medical center. Therefore, the following information is primarily intended for healthcare professionals.

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

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

Store in refrigerator (between 2 °C and 8 °C). Do not freeze.

Store in the original box to protect it from light.

Before using this medication, check that the solution does not present particles or discoloration. The solution must be colorless to light yellow. Do not use this medication if you notice it is turbid, discolored, or contains visible particles.

Medications should not be disposed of through drains or trash. Your healthcare professional will dispose of the medications that are no longer in use. This will help protect the environment.

Talvey Composition

• The active ingredient is talquetamab. Talvey is available in two different concentrations:

• 2 mg/ml – a 1.5 ml vial contains 3 mg of talquetamab
• 40 mg/ml – a 1 ml vial contains 40 mg of talquetamab

• The other components are sodium dihydrogen EDTA (E385), glacial acetic acid (E260), polisorbate 20 (E432), sodium trihydrate acetate (E262), sucrose (E473), and water for injection (see "Talvey contains sodium" in section 2).

Talvey Appearance and Packaging

Talvey is a clear yellowish liquid injectable solution.

Talvey is presented in a carton containing 1 glass vial.

Marketing Authorization Holder

Janssen-Cilag International NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

Manufacturer

Janssen Biologics B.V.

Einsteinweg 101

2333 CB Leiden

Netherlands

Janssen Pharmaceutica NV

Turnhoutseweg 30

B-2340 Beerse

Belgium

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of the summary of product characteristics:

This medicinal product has been authorized under a conditional approval. This type of approval means that it is expected that more information will be obtained about this medicinal product.

The European Medicines Agency will review the new information on this medicinal product at least once a year and this summary of product characteristics will be updated as necessary.

Other sources of information

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

This website provides this summary of product characteristics in all official languages of the European Union/European Economic Area.

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This information is intended for healthcare professionals only:

The vials of TALVEY are supplied as a ready-to-use injectable solution that does not require dilution before administration.

Do not combine vials of Talvey from different concentrations to obtain the treatment dose.

For the preparation and administration of Talvey, aseptic technique must be used.

Talvey Preparation

• Consult the following reference tables for the preparation of Talvey.

• Use Table 1 to determine the total dose, injection volume, and number of vials required based on the patient's current body weight for the 0.01 mg/kg dose using the 2 mg/ml Talvey vial.

Table 1: Dose of 0.01 mg/kg: injection volumes with the 2 mg/ml Talvey vial

ª The total dose (mg) is calculated based on the rounded injection volume (ml)

• Use Table 2 to determine the total dose, injection volume, and number of vials required based on the patient's current body weight for the 0.06 mg/kg dose using the 2 mg/ml Talvey vial.

Table 2: Dose of 0.06 mg/kg: injection volumes with the 2 mg/ml Talvey vial

ª The total dose (mg) is calculated based on the rounded injection volume (ml)

• Use Table 3 to determine the total dose, injection volume, and number of vials required based on the patient's current body weight for the 0.4 mg/kg dose using the 40 mg/ml Talvey vial.

Table 3: Dose of 0.4 mg/kg: injection volumes with the 40 mg/ml Talvey vial

ª The total dose (mg) is calculated based on the rounded injection volume (ml)

• Use Table 4 to determine the total dose, injection volume, and number of vials required based on the patient's current body weight for the 0.8 mg/kg dose using the 40 mg/ml Talvey vial.

Table 4: Dose of 0.8 mg/kg: injection volumes with the 40 mg/ml Talvey vial

ª The total dose (mg) is calculated based on the rounded injection volume (ml)

• Check that the Talvey injectable solution is clear yellowish. Do not use it if the solution is discolored, turbid, or if there are any foreign particles.
• Remove the Talvey vial from the refrigerated storage (2°C to 8°C) and equilibrate it to room temperature (15°C to 30°C) for at least 15 minutes. Do not heat the Talvey vial in any other way.
• Once equilibrated, gently move the vial for approximately 10 seconds to mix it. Do not agitate.
• Withdraw the required injection volume of Talvey from the (the) vial(s) into a suitable syringe using a transfer needle.

• Each injection volume must not exceed 2.0 ml. Divide doses that require more than 2.0 ml in an equitable manner into several syringes.

• Talvey is compatible with steel needles and syringe materials made of polypropylene or polycarbonate.
• Replace the transfer needle with another of suitable size for injection.

Talvey Administration

• Talvey must be administered by subcutaneous injection.
• Talvey must be administered by a healthcare professional with adequately trained medical staff and appropriate medical equipment for managing severe reactions, including SLC.
• Inject the required volume of Talvey into the subcutaneous tissue of the abdomen (preferred injection site). Alternatively, Talvey can be injected into the subcutaneous tissue in other sites (e.g., the thigh). If multiple injections are required, the Talvey injection sites must be at least 2 cm apart.
• Do not inject into tattoos or scars or into areas where the skin is red, bruised, sensitive, hard, or not intact.
• Unused medication and all materials that have come into contact with it will be disposed of in accordance with local regulations.