Consumer medicine information

Tecvayli

Teclistamab

BRAND INFORMATION

Brand name

Tecvayli

Active ingredient

Teclistamab

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Tecvayli.

SUMMARY CMI

TECVAYLI®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

▼ This medicine is new. Please report side effects. See the full CMI for further details.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I using TECVAYLI?

TECVAYLI is a cancer medicine that contains the active ingredient teclistamab.

TECVAYLI is used to treat adults with cancer of the bone marrow called multiple myeloma. It is used for patients who have had at least three other kinds of treatment which have not worked or have stopped working.

For more information, see Section 1. Why am I using TECVAYLI? in the full CMI.

2. What should I know before I use TECVAYLI?

Do not use if you have ever had an allergic reaction to teclistamab or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have had a stroke or seizure within the past 6 months or have had a recent vaccination or are going to have a vaccination.

Tell your doctor if you notice any new or worsening symptoms of Progressive Multifocal Leukoencephalopathy or have ever had hepatitis B infection or might now have hepatitis B infection.

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use TECVAYLI? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with TECVAYLI and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How is TECVAYLI given?

Your doctor or other healthcare professional will give the injection under the skin (called subcutaneous injection) in the stomach area or thigh. More information can be found in Section 4. How is TECVAYLI given? in the full CMI.

5. What should I know while using TECVAYLI?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are using TECVAYLI.
  • Look out for serious side effects such as signs of a condition known as 'cytokine release syndrome' (CRS), infection, 'immune effector cell-associated neurotoxicity syndrome' (ICANS)
Things you should not do
  • Do not receive live vaccines within 4 weeks before, during, or 4 weeks after treatment with TECVAYLI
Driving or using machines
  • Do not drive, use tools, or operate heavy machinery.
Looking after your medicine
  • TECVAYLI will be stored refrigerated at the hospital or clinic.
  • Do not use this medicine after the expiry date which is stated on the carton after "EXP".

For more information, see Section 5. What should I know while using TECVAYLI? in the full CMI.

6. Are there any side effects?

There are a number of side effects associated with this medicine. It is important to be aware of them so that you can identify any symptoms if they occur (see the full CMI for more details). The most common and serious side effects are: serious immune reaction called 'cytokine release syndrome'; low level of antibodies (hypogammaglobulinaemia); low levels of a type of white blood cells (neutropenia); infection; and serious immune reaction called 'immune effector cell-associated neurotoxicity syndrome' that have effects on your nervous system. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. You can report side effects to your doctor, or directly at www.tga.gov.au/reporting-problems.

WARNING: TECVAYLI may cause side effects that are serious, life-threatening or lead to death including Cytokine Release Syndrome (CRS) and neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). Call your healthcare professional right away if you develop any of the signs or symptoms listed below:
• CRS: fever, nausea, headache, fast heartbeat, feeling dizzy, and difficulty breathing
• Neurologic toxicity, including ICANS: headache, feeling confused, feeling less alert, speaking slowly, having difficulty writing, reading and understanding words.



FULL CMI

TECVAYLI®

Active ingredient(s): teclistamab

TECVAYLI as monotherapy has provisional approval in Australia and is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. The decision to approve this medicine has been made on the basis of promising results from preliminary study. More evidence is required to be submitted when available to fully confirm the benefit and safety of the medicine for this use.

Consumer Medicine Information (CMI)

This leaflet provides important information about using TECVAYLI. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using TECVAYLI.

Where to find information in this leaflet:

1. Why am I using TECVAYLI?
2. What should I know before I use TECVAYLI?
3. What if I am taking other medicines?
4. How is TECVAYLI given?
5. What should I know while using TECVAYLI?
6. Are there any side effects?
7. Product details

1. Why am I using TECVAYLI?

TECVAYLI is a cancer medicine that contains the active ingredient teclistamab.

TECVAYLI is a prescription medication for adults with cancer of the bone marrow, called multiple myeloma.

  • It is used for patients who have had at least three other kinds of treatment.
  • These treatments have not worked or have stopped working.

TECVAYLI is given alone to treat multiple myeloma.

TECVAYLI is an antibody, which is a type of protein. It has been designed to recognise and attach to specific targets in your body.

TECVAYLI targets proteins found on cells in the blood:

  • BCMA (B cell maturation antigen), found on cancer cells
  • CD3 (cluster of differentiation 3), found in your immune system

TECVAYLI works by attaching to these proteins so that your immune system can destroy the multiple myeloma cancer cells.

2. What should I know before I use TECVAYLI?

Warnings

Do not use TECVAYLI if:

  • you are allergic to teclistamab or any of the ingredients listed at the end of this leaflet.

Check with your healthcare professional if you:

  • have had a recent vaccination or are going to have a vaccination
    Do not receive live vaccines:
    - four weeks before beginning treatment with TECVAYLI
    - during treatment with TECVAYLI
    - four weeks after your final dose of TECVAYLI.
  • have had a stroke or seizure within the past 6 months
  • notice any new or worsening symptoms of Progressive Multifocal Leukoencephalopathy (PML). PML is a serious and potentially fatal brain infection. Symptoms may include, but are not limited to, blurred, loss of or double vision, difficulty speaking, weakness in an arm or a leg, a change in the way you walk or problems with your balance, persistent numbness, decreased sensation or loss of sensation, memory loss or confusion.
  • have ever had or might now have hepatitis B infection. This is because TECVAYLI could cause hepatitis B virus to become active again. Your healthcare professional will check you for signs of this infection before, during and for some time after treatment with TECVAYLI. Tell your healthcare professional if you get worsening tiredness, or yellowing of your skin or white part of your eyes.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

  • Check with your doctor if you or your partner are pregnant or intend to become pregnant.
    - Men: if your partner could become pregnant, you must use effective contraception during and for 3 months after stopping treatment with TECVAYLI. If your partner becomes pregnant while you are being treated with this medicine, tell your doctor right away.
    - Women: you must use effective contraception during and for 5 months after stopping treatment with TECVAYLI. If you become pregnant while being treated with this medicine, tell your doctor right away.
  • You and your doctor will decide if the benefit of breastfeeding is greater than the risk to your baby. If you and your doctor decide to stop taking this medicine, you should not breastfeed for 5 months after stopping treatment.

Children and Adolescents

  • Do not give TECVAYLI to children or young people below 18 years of age. This is because it is not known how the medicine will affect them.

3. What if I am taking other medicines?

Some medicines may interfere with TECVAYLI and affect how it works.

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect TECVAYLI.

4. How is TECVAYLI given?

How much to use

Your doctor or healthcare professional will work out your dose of TECVAYLI based on your body weight.

The recommended dose of TECVAYLI is:

  • First dose - 0.06 mg for each kilogram of body weight
  • Second dose - 0.3 mg for each kilogram of body weight
  • Treatment dose - 1.5 mg for each kilogram of body weight

TECVAYLI is given as follows:

  • You will receive your First dose of TECVAYLI to begin treatment
  • You will receive your Second dose 2-4 days later
  • You will then receive a 'Treatment dose' 2-4 days after your second dose
  • You will continue receiving a 'Treatment dose' once a week for as long as you are getting benefit from TECVAYLI

If you are continuing to receive benefit from TECVAYLI after 6 months, your doctor may decide that you can change to receive the 'Treatment dose' at a reduced frequency (every two weeks).

Your healthcare professional will monitor you for side effects after each of your first three doses - they will do this for 2 days after each dose. You should stay near a healthcare facility after each of the first three doses in case you have side effects. Your healthcare professional will tell you if you need to be monitored after other doses.

How to use TECVAYLI

TECVAYLI will be given to you by your healthcare professional as an injection under the skin (subcutaneous injection) in the stomach area or thigh.

Before you have TECVAYLI your healthcare professional will check:

  • Your blood counts
  • For signs of infection - an infection will be treated before you have TECVAYLI
  • If you are pregnant or breastfeeding

After you have TECVAYLI your healthcare professional will:

  • Monitor you for side effects
  • Regularly check your blood counts, as the number of blood cells and other blood components may decrease

Medicines given during treatment with TECVAYLI

Before each of your first three injections of TECVAYLI, you will be given medicines to help lower the chance of side effects. These may include:

  • Medicines for an allergic reaction (antihistamines)
  • Medicines for inflammation (corticosteroids)
  • Medicines for fever (such as paracetamol)

You may be given these medicines for later doses of TECVAYLI based on any symptoms you have.

You may be given additional medicines based on any symptoms you experience or your medical history.

If you forget to use TECVAYLI

If you cannot keep your appointment with the doctor, make sure you call your doctor right away so another appointment can be made as soon as possible.

If you use too much TECVAYLI

This medicine will be given by your healthcare professional. In the unlikely event that you are given too much (an overdose) your healthcare professional will check you for side effects.

5. What should I know while using TECVAYLI?

Things you should do

Follow your doctor's instructions carefully.

Tell your doctor if you become pregnant or intend to become pregnant.

Call your doctor straight away if you experience any of the following:

  • Signs of a condition known as 'cytokine release syndrome' (CRS). A patient card to inform you of CRS is available from your doctor and you need to always carry this card with you whilst on treatment.
  • Effects on your nervous system, which can occur days or weeks after you receive the injection, and may initially be subtle. Some of these may be signs of a serious immune reaction called 'immune effector cell-associated neurotoxicity syndrome' (ICANS).
  • Signs and symptoms of an infection.

Tell your healthcare professional if you notice any signs of the above. The symptoms are listed under “Serious side effects” in Section 6. Are there any side effects.

Remind any doctor, dentist or pharmacist you visit that you are using TECVAYLI.

Driving or using machines

Some people may feel tired, dizzy, or confused while taking TECVAYLI. Do not drive, use tools, or operate heavy machinery. Also, do not do things that could pose a danger to yourself.

Wait until at least 48 hours after receiving your third dose of TECVAYLI or as instructed by your doctor.

Looking after your medicine

TECVAYLI is stored and administered by healthcare professionals so it is unlikely that you will store this medicine at home.

TECVAYLI should be stored in a refrigerator (2°C-8°C) and kept in the original carton in order to protect from light. Do not freeze.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

TECVAYLI will be disposed of appropriately by the healthcare professionals.

Do not use this medicine after the expiry date which is stated on the carton after “EXP”. The expiry date refers to the last day of that month.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • decreased appetite
  • nausea, diarrhoea, constipation, vomiting
  • headache
  • fever
  • feeling very tired
  • nerve damage that may cause tingling, numbness, pain or loss of pain sensation
  • pain or muscle aches
  • bleeding, which can be severe (haemorrhage)
  • swollen hands, ankles or feet (oedema)
  • lung infection (pneumonia)
  • infected nose, sinuses or throat (upper respiratory tract infection)
  • skin infection causing redness (cellulitis)
  • skin reactions at or near the injection site, including redness of the skin, itching, swelling, pain, bruising, rash, bleeding
  • low level of oxygen (hypoxia)
  • being short of breath (dyspnoea)
  • cough
  • high blood pressure (hypertension)

Abnormal blood test results such as:

  • a low levels of red blood cells (anaemia)
  • low levels of 'platelets' (cells that help blood to clot)
  • low number of white blood cells (leukopenia)
  • low levels of a type of white blood cells (lymphopenia)
  • low level of 'phosphate', 'magnesium' or 'potassium' in the blood (hypophosphataemia, hypomagnesaemia or hypokalaemia)
  • increased level of 'calcium' (hypercalcaemia)
  • increased 'alkaline phosphatase' in the blood
  • low level of 'calcium' or 'sodium' in the blood (hypocalcaemia or hyponatraemia)
  • high level of 'potassium' in the blood (hyperkalaemia)
  • low level of 'albumin' in the blood (hypoalbuminaemia)
  • increased level of 'gamma-glutamyltransferase' in the blood (blood gamma-glutamyltransferase increase)
  • increased level of liver enzymes 'transaminases' in the blood (blood transaminase increase)
  • increased level of 'creatinine' in the blood (blood creatinine increase)
  • increased level of 'amylase' in the blood (hyperamylasaemia)
  • increased level of 'lipase' in the blood (hyperlipasemia)
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • serious immune reaction that may cause fever, nausea, headache, fast heart beat, feeling dizzy, and difficulty breathing ('cytokine release syndrome')
  • low level of antibodies called 'immunoglobulins' in the blood, which may make infections more likely (hypogammaglobulinaemia)
  • low levels of a type of white blood cells (neutropenia)
  • low number of a type of white blood cell (neutrophils) with a fever
  • infection, which may include fever, chills, shivering, cough, shortness of breath, rapid breathing and rapid pulse
  • severe infection throughout the body (sepsis)
  • COVID-19 infection caused by a virus called coronavirus (SARS-CoV-2)
  • effects on your nervous system, which may include headache, feeling confused, feeling less alert, speaking slowly, having difficulty writing, reading and understanding words. Some of these symptoms may be signs of a serious immune reaction called 'immune effector cell-associated neurotoxicity syndrome' (ICANS)
  • change in brain function (encephalopathy)
  • A serious and potentially fatal brain infection called Progressive Multifocal Leukoencephalopathy (PML). Some of the symptoms include blurred, loss of or double vision, difficulty speaking, weakness in an arm or a leg, a change in the way you walk or problems with your balance, persistent numbness, decreased sensation or loss of sensation and memory loss or confusion.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What TECVAYLI contains

Active ingredient
(main ingredient)		teclistamab
Other ingredients
(inactive ingredients)		disodium edetate (EDTA)
glacial acetic acid
polysorbate 20
sodium acetate trihydrate
sucrose
water for injections

Do not take this medicine if you are allergic to any of these ingredients.

What TECVAYLI looks like

TECVAYLI is a solution for injection and is a colourless to light yellow liquid.

TECVAYLI is supplied as a carton pack containing 1 glass vial.

  • teclistamab 30 mg/3 mL (10 mg/mL) AUST R 387621
  • teclistamab 153 mg/1.7 mL (90 mg/mL) AUST R 387622

Who distributes TECVAYLI

Janssen-Cilag Pty Ltd
1-5 Khartoum Road Macquarie Park NSW 2113
Australia
Telephone: 1800 226 334

NZ Office: Auckland New Zealand
Telephone: 0800 800 806

This leaflet was prepared on 24 March 2025.

Published by MIMS May 2025

BRAND INFORMATION

Brand name

Tecvayli

Active ingredient

Teclistamab

Schedule

S4

 

1 Name of Medicine

Teclistamab.

2 Qualitative and Quantitative Composition

Tecvayli (teclistamab) is a humanised immunoglobulin G4-proline, alanine, alanine (IgG4-PAA) bispecific antibody targeting the B cell maturation antigen (BCMA) and CD3 receptors, produced in a mammalian cell line (Chinese hamster ovary [CHO]) using recombinant DNA technology.
Tecvayli is available in the following presentations:
Each 3 mL vial contains 30 mg of teclistamab (10 mg of teclistamab per mL).
Each 1.7 mL vial contains 153 mg of teclistamab (90 mg of teclistamab per mL).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Tecvayli is a colourless to light yellow preservative-free solution for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Tecvayli as monotherapy has provisional approval in Australia and is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
The decision to approve this indication has been made on the basis of the overall response rate in a single arm study. Continued approval of this indication depends on verification and description of benefit in confirmatory trials.

4.2 Dose and Method of Administration

Treatment with Tecvayli should be initiated and supervised by physicians experienced in the treatment of multiple myeloma.

Dosage - adults (18 years of age and older).

Tecvayli should be administered by subcutaneous injection only.
Administer pretreatment medications prior to each dose of the Tecvayli step-up dosing schedule (see Pretreatment medications).

Recommended dosing schedule.

The recommended dosing schedule for Tecvayli is provided in Table 1. The recommended dosage of Tecvayli is step-up doses of 0.06 mg/kg and 0.3 mg/kg followed by 1.5 mg/kg once weekly until disease progression or unacceptable toxicity.
In patients who have a complete response or better for a minimum of 6 months, a reduced dosing frequency of 1.5 mg/kg every two weeks until disease progression or unacceptable toxicity may be considered (see Section 5.1 Pharmacodynamic Properties, Clinical trials).
Administer Tecvayli according to the step-up dosing schedule in Table 1 to reduce the incidence and severity of cytokine release syndrome (CRS). Due to the risk of cytokine release syndrome, instruct patients to remain within proximity of a healthcare facility and monitor patients for signs and symptoms daily for 48 hours after administration of all doses within the Tecvayli step-up dosing schedule (see Administration; see Section 4.4 Special Warnings and Precautions for Use, Cytokine release syndrome (CRS)).
Failure to follow the recommended doses or dosing schedule for initiation of therapy or re-initiation of therapy after dose delays may result in increased frequency and severity of adverse events related to mechanism of action, particularly cytokine release syndrome (see Dosage modifications; see Section 4.4 Special Warnings and Precautions for Use, Cytokine release syndrome (CRS)).
For guidance regarding restarting therapy with Tecvayli after dose delays, see Restarting Tecvayli after dose delays.

Pretreatment medications.

Administer the following pretreatment medications 1 to 3 hours before each dose of the Tecvayli step-up dosing schedule to reduce the risk of cytokine release syndrome (see Section 4.4 Special Warnings and Precautions for Use, Cytokine release syndrome (CRS); Section 4.8 Adverse Effects (Undesirable Effects)).
Corticosteroid (oral or intravenous dexamethasone, 16 mg or equivalent).
Antihistamine (oral or intravenous diphenhydramine, 50 mg or equivalent).
Antipyretics (oral paracetamol 500 mg to 1000 mg).
Administration of pretreatment medications may be required prior to administration of subsequent doses of Tecvayli in the following patients: (see Dosage modifications).
Patients who repeat doses within the Tecvayli step-up dosing schedule following a dose delay (see Restarting Tecvayli after dose delays).
Patients who experienced CRS following the prior dose of Tecvayli (see Dosage modifications).

Prophylaxis for herpes zoster virus reactivation.

Prior to starting treatment with Tecvayli, anti-viral prophylaxis should be considered for the prevention of herpes zoster virus reactivation per local institutional guidelines.

Restarting Tecvayli after dose delays.

If a dose of Tecvayli is delayed, restart therapy based on the recommendations listed in Table 2 and resume the treatment schedule accordingly (see Dosage - adults (18 years of age and older)). Administer pretreatment medications as indicated in Table 2 and monitor patients following administration of Tecvayli accordingly (see Pretreatment medications and Administration).

Dosage modifications.

Do not skip step-up doses of Tecvayli.
Dose reductions of Tecvayli are not recommended.
Dose delays may be required to manage toxicities related to Tecvayli (see Section 4.4 Special Warnings and Precautions for Use).
See Table 3 for recommended actions for adverse reactions following administration of Tecvayli.

Management of severe adverse reactions.

Cytokine release syndrome (CRS).

CRS, including life-threatening or fatal reactions, may occur in patients receiving Tecvayli.
Identify CRS based on clinical presentation (see Section 4.4 Special Warnings and Precautions for Use, Cytokine release syndrome (CRS)). Evaluate and treat other causes of fever, hypoxia, and hypotension.
If CRS is suspected, withhold Tecvayli until the adverse reaction resolves (see Table 3) and manage according to the recommendations in Table 4. Administer supportive care for CRS (including but not limited to anti-pyretic agents, intravenous fluid support, vasopressors, supplemental oxygen, etc.) as appropriate. Consider laboratory testing to monitor for disseminated intravascular coagulation (DIC), haematology parameters, as well as pulmonary, cardiac, renal, and hepatic function.

Neurologic toxicities.

Serious or life-threatening neurological toxicities, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) with or without concurrent CRS, may follow treatment with Tecvayli.
General management for neurologic toxicity (e.g. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) with or without concurrent CRS) is summarised in Table 5.
At the first sign of neurologic toxicity including ICANS, consider neurology evaluation. Rule out other causes of neurologic symptoms. Provide intensive care and supportive therapy for severe or life-threatening neurologic toxicities (see Section 4.4 Special Warnings and Precautions for Use, Neurologic toxicities). Withhold Tecvayli as indicated in Table 3.

Use in hepatic impairment.

No formal studies of Tecvayli in patients with hepatic impairment have been conducted.
Based on population pharmacokinetic analyses, no dose adjustment is recommended for patients with mild hepatic impairment (see Section 5.2 Pharmacokinetic Properties).

Use in renal impairment.

No formal studies of Tecvayli in patients with renal impairment have been conducted.
Based on population pharmacokinetic analyses, no dose adjustment is recommended for patients with mild or moderate renal impairment (see Section 5.2 Pharmacokinetic Properties).

Administration.

Strictly follow the preparation and administration instructions provided in this section to minimise potential dosing errors with Tecvayli 10 mg/mL vial and Tecvayli 90 mg/mL vial.
Tecvayli should be administered via subcutaneous injection only. Do not administer Tecvayli intravenously.
Tecvayli should be administered by a healthcare professional with adequately trained medical personnel and appropriate medical equipment to manage severe reactions, including cytokine release syndrome (see Section 4.4 Special Warnings and Precautions for Use, Cytokine release syndrome (CRS)).
Tecvayli 10 mg/mL vial and Tecvayli 90 mg/mL vial are supplied as ready-to-use solution for injection that do not need dilution prior to administration.
Tecvayli vials of different concentrations should not be combined to achieve treatment dose.
Use aseptic technique to prepare and administer Tecvayli.

Preparation of Tecvayli.

Verify the prescribed dose for each Tecvayli injection. To minimise errors, use the following tables to prepare Tecvayli injection.
Use Table 6 to determine total dose, injection volume and number of vials required based on patient's actual body weight for step-up dose 1 using Tecvayli 10 mg/mL.
Use Table 7 to determine total dose, injection volume and number of vials required based on patient's actual body weight for step-up dose 2 using Tecvayli 10 mg/mL.
Use Table 8 to determine total dose, injection volume and number of vials required based on patient's actual body weight for the treatment dose using Tecvayli 90 mg/mL.
Remove the appropriate strength Tecvayli vial from refrigerated storage 2°C-8°C and equilibrate to ambient temperature 15°C-30°C for at least 15 minutes prior to administration. Do not warm Tecvayli in any other way.
Once equilibrated, gently swirl the vial for approximately 10 seconds to mix. Do not shake.
Withdraw the required injection volume of Tecvayli from the vial(s) into an appropriately sized syringe using a transfer needle.
Each injection volume should not exceed 2.0 mL. Divide doses requiring greater than 2.0 mL equally into multiple syringes.
Tecvayli is compatible with stainless steel injection needles and polypropylene or polycarbonate syringe material.
Visually inspect Tecvayli for particulate matter and discolouration prior to administration. Do not use if the solution is discoloured, or cloudy, or if foreign particles are present.
Tecvayli solution for injection is colourless to light yellow.
Replace the transfer needle with an appropriately sized needle for injection.

Administration of Tecvayli.

Inject the required volume of Tecvayli into the subcutaneous tissue of the abdomen (preferred injection site). Alternatively, Tecvayli may be injected into the subcutaneous tissue at other sites (e.g. thigh). If multiple injections are required, Tecvayli injections should be at least 2 cm apart.
Do not inject into tattoos or scars or areas where the skin is red, bruised, tender, hard or not intact.
Any unused medicinal product or waste material should be disposed in accordance with local requirements.
Product is for single use in one patient only. Discard any residue.

Storage.

If Tecvayli is not used immediately, store at 2-8°C or up to 30°C for a maximum of 20 hours. Discard after 20 hours, if not used.

Monitoring.

Instruct patients to remain within proximity of a healthcare facility and monitor patients daily for 48 hours for signs and symptoms of CRS after administration of all doses within the Tecvayli step-up dosing schedule (see Table 1; Management of severe adverse reactions; see Section 4.4 Special Warnings and Precautions for Use, Cytokine release syndrome (CRS)).

4.3 Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients listed in Section 6.1.

4.4 Special Warnings and Precautions for Use

Cytokine release syndrome (CRS).

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, may occur in patients receiving Tecvayli. In the MajesTEC-1 study, the median time to onset of CRS was 2 (Range: 1 to 6) days after the most recent dose with a median duration of 2 (Range: 1 to 9) days.
Clinical signs and symptoms of CRS may include, but are not limited to, fever, chills, hypotension, tachycardia, hypoxia, headache, and elevated liver enzymes. Potentially life-threatening complications of CRS may include cardiac dysfunction, adult respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).
Initiate therapy according to Tecvayli step-up dosing schedule to reduce risk of CRS (see Table 1). Failure to follow the recommended doses or dosing schedule for initiation of therapy or re-initiation of therapy after dose delays may result in increased frequency and severity of adverse events related to mechanism of action.
Administer pretreatment medications (corticosteroids, antihistamine, and antipyretics) prior to each dose of the Tecvayli step-up dosing schedule to reduce risk of CRS and monitor patients following administration accordingly (see Section 4.2 Dose and Method of Administration, Pretreatment medications and Administration). In patients who experienced CRS following their previous dose, administer pretreatment medications prior to the next dose of Tecvayli.
Counsel patients to seek medical attention should signs or symptoms of CRS occur. A patient card to inform patients of CRS associated with Tecvayli is available. The patient card should be kept with the patient at all times whilst on treatment.
At the first sign of CRS, immediately evaluate patient for hospitalisation and institute treatment with supportive care, tocilizumab and/or corticosteroids, based on severity as indicated in Table 4.
In MajesTEC-1, tocilizumab, corticosteroids, and tocilizumab in combination with corticosteroids were used to treat 32%, 11% and 3% of CRS events, respectively. The use of myeloid growth factors, particularly granulocyte macrophage-colony stimulating factor (GM-CSF), should be avoided during CRS.
Withhold treatment with Tecvayli until CRS resolves as indicated in Table 3 (see Section 4.2 Dose and Method of Administration, Management of severe adverse reactions).

Neurologic toxicities.

Serious, life-threatening or fatal neurologic toxicities, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), occurred following treatment with Tecvayli. In MajesTEC-1, the majority of neurologic toxicity events were Grade 1 and Grade 2 (see Section 4.8 Adverse Effects (Undesirable Effects)). The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.
Monitor patients for signs or symptoms of neurologic toxicities during treatment and treat promptly.
Counsel patients to seek medical attention should signs or symptoms of neurologic toxicity occur. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and institute treatment based on severity as indicated in Table 5 (see Section 4.2 Dose and Method of Administration, Management of severe adverse reactions).
For ICANS or other neurologic toxicities, withhold treatment with Tecvayli as indicated in Table 3 and manage adverse reactions based on recommendations in Table 5.

Infections.

Severe, life-threatening or fatal infections have been reported in patients receiving Tecvayli (see Section 4.8 Adverse Effects (Undesirable Effects)). New or reactivated viral infections occurred during therapy with Tecvayli.
Monitor patients for signs and symptoms of infection prior to and during treatment with Tecvayli and treat appropriately. Prophylactic antimicrobials should be administered according to local institutional guidelines.
Withhold treatment with Tecvayli as indicated in Table 3 (see Section 4.2 Dose and Method of Administration, Dosage modifications).
Progressive multifocal leukoencephalopathy (PML), which can be fatal, has also been reported in patients receiving Tecvayli (see Section 4.8 Adverse Effects (Undesirable Effects)). Monitor any new onset of or changes in pre-existing neurological signs or symptoms. If PML is suspected, withhold treatment with Tecvayli and initiate appropriate diagnostic testing. Discontinue Tecvayli if PML is confirmed.

Hepatitis B virus reactivation.

Hepatitis B virus reactivation can occur in patients treated with drugs directed against B cells, and in some cases, may result in fulminant hepatitis, hepatic failure, and death.
Patients with evidence of positive HBV serology should be monitored for clinical and laboratory signs of HBV reactivation while receiving Tecvayli, and for at least six months following the end of treatment.
In patients who develop reactivation of HBV while on Tecvayli, withhold treatment with Tecvayli as indicated in Table 3 and manage per local institutional guidelines (see Section 4.2 Dose and Method of Administration, Dosage modifications).

Hypogammaglobulinaemia.

Hypogammaglobulinaemia has been reported in patients receiving Tecvayli (see Section 4.8 Adverse Effects (Undesirable Effects)).
Monitor immunoglobulin levels during treatment with Tecvayli and treat according to local institutional guidelines, including infection precautions, antibiotic or antiviral prophylaxis, and administration of immunoglobulin replacement therapy.

Vaccines.

Immune response to vaccines may be reduced when taking Tecvayli.
The safety of immunisation with live viral vaccines during or following Tecvayli treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 4 weeks prior to the start of treatment, during treatment, and at least 4 weeks after treatment.

Neutropenia.

Neutropenia and febrile neutropenia have been reported in patients who received Tecvayli (see Section 4.8 Adverse Effects (Undesirable Effects)).
Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines.
Patients with neutropenia should be monitored for signs of infection.
Withhold treatment with Tecvayli based on severity as indicated in Table 3 (see Section 4.2 Dose and Method of Administration, Dosage modifications).

Use in the elderly (65 years of age and older).

Of the 165 patients treated with Tecvayli in MajesTEC-1 at the recommended dose, 48% were 65 years of age or older, and 15% were 75 years of age or older. No overall differences in safety or effectiveness were observed between these patients and younger patients. No dose adjustment is necessary (see Section 4.2 Dose and Method of Administration; Section 5.2 Pharmacokinetic Properties).

Paediatric use (17 years of age and younger).

The safety and efficacy of Tecvayli have not been established in paediatric patients aged 17 years and younger.

Effects of laboratory tests.

No data available.

Effect on QT/QTc interval and cardiac electrophysiology.

At the recommended treatment dose (1.5 mg/kg) of Tecvayli, no clinically relevant QTc prolongation has been observed.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No drug interaction studies have been performed with Tecvayli.
The initial release of cytokines associated with the start of Tecvayli treatment could suppress CYP450 enzymes. Based on physiologically based pharmacokinetic (PBPK) modelling, the highest risk of drug-drug interaction is predicted to be from initiation of Tecvayli step-up dosing schedule up to 7 days after the first treatment dose or during a CRS event. During this time period, monitor for toxicity or drug concentrations (e.g. cyclosporine) in patients who are receiving concomitant CYP450 substrates with a narrow therapeutic index. The dose of the concomitant drug should be adjusted as needed.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no data on the effect of Tecvayli on fertility.
No studies have been conducted to evaluate the effects of teclistamab on fertility in males or females.
(Category C)
There are no available data on the use of Tecvayli in pregnant women or animal data to assess the risk of Tecvayli in pregnancy. Teclistamab causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. Human IgG is known to cross the placenta after the first trimester of pregnancy.
Therefore, teclistamab has the potential to be transmitted from the mother to the developing fetus.
Tecvayli is not recommended for women who are pregnant. Tecvayli is associated with hypogammaglobulinaemia, therefore, assessment of immunoglobulin levels in newborns of mothers treated with Tecvayli should be considered.

Pregnancy testing.

Pregnancy status for females of child-bearing potential should be verified prior to starting treatment with Tecvayli.

Contraception.

Advise females of reproductive potential to use effective contraception during treatment and for five months after the final dose of Tecvayli.
Advise male patients with a female partner of reproductive potential to use effective contraception during treatment and for three months after the last dose of Tecvayli.
 It is not known whether teclistamab is excreted in human or animal milk, affects breastfed infants or affects milk production. Because of the potential for serious adverse reactions in breastfed infants from Tecvayli, advise patients not to breastfeed during treatment with Tecvayli and for at least five months after the last dose.

4.7 Effects on Ability to Drive and Use Machines

Due to the potential for ICANS, patients receiving Tecvayli are at risk of depressed level of consciousness. Patients should avoid driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of Tecvayli step-up dosing schedule and in the event of new onset of any neurological symptoms (Table 1) (see Section 4.2 Dose and Method of Administration).

4.8 Adverse Effects (Undesirable Effects)

The safety data of Tecvayli was evaluated in MajesTEC-1, which included 165 adult patients with relapsed or refractory multiple myeloma who received the recommended dose regimen of subcutaneous Tecvayli as monotherapy. The median duration of Tecvayli treatment was 8.5 (range: 0.2 to 24.4) months.
The most frequent adverse reactions of any grade (≥ 20%) in patients were hypogammaglobulinaemia (75%), cytokine release syndrome (72%), neutropenia (71%), anaemia (55%), musculoskeletal pain (52%), fatigue (41%), thrombocytopenia (40%), injection site reaction (38%), upper respiratory tract infection (37%), lymphopenia (35%), diarrhoea (28%), pneumonia (28%), nausea (27%), pyrexia (27%), headache (24%) cough (24%), constipation (21%), and pain (21%).
Serious adverse reactions were reported in 65% patients who received Tecvayli. Serious adverse reactions reported in ≥ 2% of patients included pneumonia (16%), COVID-19 (15%), cytokine release syndrome (8%), sepsis (7%), pyrexia (5%), musculoskeletal pain (5%), acute kidney injury (4.8%), diarrhoea (3.0%), cellulitis (2.4%), hypoxia (2.4%), febrile neutropenia (2.4%), and encephalopathy (2.4%).
Dose interruptions (dose delays and dose skips) of Tecvayli due to adverse reactions occurred in 65% of patients. The most frequent adverse reactions (≥ 5%) leading to dose interruptions were neutropenia (26%), COVID-19 (12%), pneumonia (10%), cytokine release syndrome (8%) and pyrexia (7%).
Dose reduction of Tecvayli due to adverse reaction occurred in one patient (0.6%) due to neutropenia.
Permanent discontinuation of Tecvayli due to adverse reactions occurred in two patients (1.2%), both due to infection.
Table 9 summarises adverse reactions reported in patients who received Tecvayli.
Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); not known (frequency cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing frequency.

Description of selected adverse reactions.

Cytokine release syndrome.

In Majes-TEC-1 (N=165), CRS was reported in 72% of patients following treatment with Tecvayli. One-third (33%) of patients experienced more than one CRS event. Most patients experienced CRS following step-up dose 1 (44%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of Tecvayli. Most CRS events were Grade 1 (50%) and Grade 2 (21%). Less than one percent (0.6%) of CRS events were Grade 3, and no Grade 4 or fatal events occurred. Tocilizumab, corticosteroids, and tocilizumab in combination with corticosteroids were used to treat 32%, 11% and 3% of CRS events, respectively.
The most frequent (≥ 3%) signs and symptoms associated with CRS were fever (72%), hypoxia (13%), chills (12%), hypotension (12%), sinus tachycardia (7%), headache (7%), and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation) (3.6% each).

Neurologic toxicities.

In Majes-TEC-1 (N=165), neurologic toxicities were reported in 15% of patients receiving Tecvayli. Most neurologic toxicity events were Grade 1 (8.5%), Grade 2 (5.5%) and Grade 4 (0.6%). The most frequently reported neurologic toxicity was headache (8.5%).
ICANS was reported in 3% of patients receiving Tecvayli at the recommended dose. The most frequent clinical manifestations of ICANS reported were confusional state (1.2%) and dysgraphia (1.2%).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Symptoms and signs.

The maximum tolerated dose of teclistamab has not been determined. In clinical trials, doses of up to 6 mg/kg have been administered.

Treatment.

In the event of an overdose, the patient should be monitored for any signs or symptoms of adverse effects and appropriate symptomatic treatment should be instituted immediately.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: other monoclonal antibodies and antibody drug conjugates, ATC code: L01FX24.
Within the first month of treatment with teclistamab, activation and redistribution of T-cells, reduction of B-cells and induction of serum cytokines were observed.
Within one month, the majority of responders had reduction in soluble BCMA, and a greater reduction in soluble BCMA was observed in patients with deeper responses to teclistamab.

Immunogenicity.

Patients treated with subcutaneous teclistamab monotherapy (N=238) in MajesTEC-1 were evaluated for antibodies to teclistamab using an electrochemiluminescence-based immunoassay. One patient (0.4%) developed antibodies to teclistamab of low titre which were neutralising.

Mechanism of action.

Teclistamab is a bispecific antibody that targets the CD3 receptor expressed on the surface of T cells and B cell maturation antigen (BCMA), which is expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells.
In vitro, teclistamab activated T-cells, caused the release of various proinflammatory cytokines, and resulted in the lysis of multiple myeloma cells.

Clinical trials.

The efficacy of Tecvayli monotherapy was evaluated in patients with relapsed or refractory multiple myeloma in a single-arm, open-label, multicentre, study (MajesTEC-1 (MMY1001)). The study included patients who had previously received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody. The study excluded patients who experienced stroke or seizure within the past 6 months and patients with active or documented history of autoimmune disease, with the exception of vitiligo, type 1 diabetes and prior autoimmune thyroiditis.
Patients received initial step-up doses of 0.06 mg/kg and 0.3 mg/kg of Tecvayli administered subcutaneously followed by the treatment dose of Tecvayli 1.5 mg/kg administered subcutaneously once weekly thereafter until disease progression or unacceptable toxicity (see Section 4.2 Dose and Method of Administration, Dosage - adults (18 years of age and older)).
Patients who had a complete response (CR) or better for a minimum of 6 months were eligible to reduce dosing frequency to 1.5 mg/kg subcutaneously every two weeks until disease progression or unacceptable toxicity (see Section 4.2 Dose and Method of Administration, Dosage - adults (18 years of age and older)).
The median duration between step-up dose 1 and step-up dose 2 was 2.9 (range: 2-7) days. The median duration between step-up dose 2 and the initial treatment dose was 3.9 (range: 2-9) days. Patients were hospitalised for monitoring for at least 48 hours after administration of each dose of the Tecvayli step-up dosing schedule.
The efficacy population included 150 patients. The median age was 64.5 (range: 33-84) years with 15% of patients ≥ 75 years of age; 59% were male; 89% were White, 4% were Black, 2% were Asian. The International Staging System (ISS) at study entry was 53% in Stage I, 35% in Stage II, and 11% in Stage III. High-risk cytogenetics (presence of del(17p), t(4;14) or t(14; 16)) were present in 24% of patients. Eighteen percent of patients had extramedullary plasmacytomas.
The median time since initial diagnosis of multiple myeloma to enrolment was 6.1 (range: 0.8 22.7) years. The median number of prior therapies was 5 (range: 2-14) with 21% of patients who received 3 prior lines of therapy. Eighty-two percent of patients received prior stem cell transplantation. All patients had received prior therapy with a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody, and 77% were triple-class refractory (refractory to PI, an IMiD agent and an anti-CD38 monoclonal antibody).
Efficacy results were based on overall response rate as determined by the Independent Review Committee (IRC) assessment using International Myeloma Working Group (IMWG) 2016 criteria (see Table 10 and Table 11).

5.2 Pharmacokinetic Properties

The Cmax and AUCtau of teclistamab after the first subcutaneous treatment dose increase proportionally over a dosage range of 0.08 mg/kg to 3 mg/kg (0.05 to 2 times the approved recommended treatment dosage). Ninety percent of steady state exposure was achieved after 12 weekly treatment doses. The mean accumulation ratio between the first and 13th weekly treatment dose of teclistamab 1.5 mg/kg was 4.2-fold for Cmax, 4.1-fold for Ctrough, and 5.3-fold for AUCtau. See Table 12.

Absorption.

The mean bioavailability of teclistamab was 72% when administered subcutaneously. The median (range) Tmax of teclistamab after the first and 13th weekly treatment doses were 139 (19 to 168) hours and 72 (24 to 168) hours, respectively.

Distribution.

Based on the population pharmacokinetic model, mean volume of distribution was 5.63 L (29% coefficient of variation (CV)).

Metabolism and excretion.

Population pharmacokinetic analysis showed that teclistamab clearance decreases over time, with a mean (CV%) maximal reduction from baseline to the 13th weekly treatment dose of 40.8% (56%). The geometric mean (CV%) clearance is 0.472 L/day (64%) at the 13th weekly treatment dose. Patients who discontinue teclistamab after the 13th weekly treatment dose are expected to have a 50% reduction from Cmax in teclistamab concentration at a median (5th to 95th percentile) time of 15 (7 to 33) days after Tmax and a 97% reduction from Cmax in teclistamab concentration at a median time of 69 (32 to 163) days after Tmax.
Population pharmacokinetic analysis (based on MajesTEC-1) showed that soluble BCMA levels did not impact teclistamab serum concentrations.

Special populations.

Renal impairment.

No formal studies of Tecvayli in patients with renal impairment have been conducted.
Results of population pharmacokinetic analyses indicate that mild (60 mL/min/1.73 m2 ≤ estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2) or moderate (30 mL/min/1.73 m2 ≤ eGFR < 60 mL/min/1.73 m2) renal impairment did not significantly influence the pharmacokinetics of teclistamab. Limited data are available from patients with severe renal impairment.

Hepatic impairment.

No formal studies of Tecvayli in patients with hepatic impairment have been conducted.
Results of population pharmacokinetic analyses indicate that mild hepatic impairment (total bilirubin > 1 to 1.5 times upper limit of normal (ULN) and any aspartate aminotransferase (AST), or total bilirubin ≤ ULN and AST > ULN) did not significantly influence the pharmacokinetics of teclistamab. No data are available in patients with moderate and severe hepatic impairment.

Age and sex.

The pharmacokinetics of Tecvayli in paediatric patients have not been investigated.
Results of population pharmacokinetic analyses indicate that age (24 to 84 years) and sex did not influence the pharmacokinetics of teclistamab.

5.3 Preclinical Safety Data

Genotoxicity.

No genotoxicity studies have been performed to assess the genotoxic potential of teclistamab. As a large protein molecule, teclistamab is not expected to interact directly with DNA or other chromosomal material.

Carcinogenicity.

No carcinogenicity studies have been performed to assess the carcinogenic potential of teclistamab.

6 Pharmaceutical Particulars

6.1 List of Excipients

Disodium edetate (EDTA), glacial acetic acid, polysorbate 20, sodium acetate trihydrate, sucrose, water for injections.

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store at 2°C to 8°C. Refrigerate, do not freeze.
Store in the original carton in order to protect from light.

6.5 Nature and Contents of Container

3 mL solution for injection in a Type 1 glass vial with an elastomeric closure and aluminium seal with a flip off button containing 30 mg of sterile teclistamab (10 mg/mL). Pack size of 1 vial.
1.7 mL solution for injection in a Type 1 glass vial with an elastomeric closure and aluminium seal with a flip off button containing 153 mg of sterile teclistamab (90 mg/mL). Pack size of 1 vial.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

CAS number.

2119595-80-9.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes