Columvi 10 mg concentrate for solution for infusion

Patient Information Leaflet

Introduction

Package Leaflet: Information for the patient

Columvi 2.5 mg concentrate for solution for infusion

Columvi 10 mg concentrate for solution for infusion

glofitamab

This medicinal product is subject to additional monitoring, which will allow for faster identification of new safety information. You can help by reporting any side effects you may experience. Section 4 at the end of this leaflet contains information on how to report side effects.

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

• Keep this leaflet, as you may need to refer to it again.

• Your doctor will provide you with a patient alert card. Read it carefully and follow the instructions it contains. Always carry this patient alert card with you.

• Always show the patient alert card to your doctor, nurse, or if you visit a hospital.

• If you have any questions, consult your doctor or nurse.

• If you experience any side effects, consult your doctor or nurse, even if they are side effects not listed in this leaflet. See section 4.

Leaflet Contents

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

1. What Columvi is and what it is used for

What Columvi is

Columvi is a cancer medicine that contains the active substance glofitamab.

What Columvi is used for

Columvi is used to treat adults with a cancer called "diffuse large B-cell lymphoma" (DLBCL). Columvi may be given alone (as monotherapy) or together with other medicines known as chemotherapy.

• Columvi is given as monotherapy when the cancer has come back (relapsed) or did not respond to previous treatments (refractory), and the patient has already received two or more prior therapies.
• Columvi is given in combination with the medicines gemcitabine and oxaliplatin when the cancer has come back (relapsed) or has not responded to previous treatments (resistant), and the patient is not eligible for stem cell transplant.

Diffuse large B-cell lymphoma is a cancer that affects part of your immune system (the body's defences).

• It affects a type of white blood cells called "B-lymphocytes".
• In DLBCL, B-lymphocytes multiply uncontrollably and accumulate in tissues.

How Columvi works

• The active substance in Columvi, glofitamab, is a bispecific monoclonal antibody, a type of protein that binds to two specific targets in the body. It binds to a specific protein on the surface of B-lymphocytes, including cancerous B-cells, and also to another protein on the surface of T-lymphocytes (another type of white blood cell). This activates the T-lymphocytes and causes them to multiply. This, in turn, leads to the destruction of B-lymphocytes, including cancer cells.

2. What you need to know before using Columvi

Do not use Columvi

• if you are allergic to glofitamab or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to obinutuzumab, another medicine given before starting treatment with Columvi (see also section 3 "How Columvi is administered"), or to any of the other ingredients of this medicine.

If you are unsure, speak with your doctor or nurse before using Columvi.

Warnings and precautions

Talk to your doctor before starting to use Columvi if:

• you have an infection
• you have had a long-term (chronic) infection or an infection that keeps coming back (recurrent)
• you have or have had any kidney, liver, or heart problems
• you are planning to get vaccinated in the near future

If any of the above apply to you (or you are unsure), contact your doctor before receiving Columvi.

Pay attention to serious side effects.

Some adverse reactions to Columvi are serious and potentially life-threatening. These may occur at any time during treatment with Columvi.

Tell your doctor immediately if you experience any of the following adverse reactions while receiving Columvi. The symptoms of each adverse reaction are listed in section 4.

• Cytokine release syndrome – this is an exaggerated inflammatory condition associated with medicines that stimulate T cells, characterized by fever and multi-organ deterioration. Cytokine release syndrome is most likely during cycle 1 after administration of Columvi (see section 3 "How Columvi is administered"). Close monitoring is required.

Before each infusion, you should be given medications to help reduce the potential adverse effects of cytokine release syndrome.

• Immune effector cell-associated neurotoxicity syndrome – effects on the nervous system. Symptoms include confusion, disorientation, decreased alertness, seizures, or difficulty writing and/or speaking. Close monitoring is required.
• Tumor lysis syndrome – some people may develop abnormal levels of certain salts in the blood (such as potassium and uric acid) caused by the rapid breakdown of cancer cells during treatment. Your doctor or nurse will perform blood tests to monitor your condition. Before each infusion, you should be well hydrated and given medications that may help reduce high uric acid levels. These may help reduce the potential adverse effects of tumor lysis syndrome.
• Tumor flare – a reaction to certain medicines that act on the immune system, which appears similar to a worsening of cancer
• Infections – you may have signs of infection, which vary depending on where in the body the infection is located.

If you have or think you may have any of the symptoms listed above, inform your doctor immediately.

Your doctor may:

• give you other medicines to reduce symptoms and prevent complications,
• temporarily interrupt your treatment, or
• stop your treatment completely.

Children and adolescents

This medicine must not be given to children or adolescents under 18 years of age. This is because Columvi has not been studied in this age group.

Other medicines and Columvi

Tell your doctor or nurse if you are taking, have recently taken, or might need to take any other medicines. This includes medicines obtained without a prescription and herbal medicines.

Pregnancy and contraception

• If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.
• You must not be given Columvi if you are pregnant. This is because Columvi may harm the unborn baby.
• If you can become pregnant, you must use an effective method of contraception during treatment with Columvi and for 2 months after the last dose.
• If you become pregnant while being treated with Columvi, inform your doctor immediately.

Breast-feeding

You must not breast-feed during treatment with Columvi and for 2 months after the last dose. This is because it is unknown whether Columvi passes into human milk and could affect the breast-fed baby.

Driving and using machines

Columvi may affect your ability to drive, ride a bicycle, or operate tools or machinery.

Do not drive, ride a bicycle, or use tools or machinery for at least 48 hours after each of your first two doses of Columvi, or if you develop symptoms of immune effector cell-associated neurotoxicity syndrome (such as confusion, disorientation, decreased alertness, seizures, or difficulty writing and/or speaking) and/or symptoms of cytokine release syndrome (such as fever, rapid heartbeat, dizziness or lightheadedness, chills, or difficulty breathing). If you currently have these symptoms, avoid these activities and contact your doctor, nurse, or pharmacist. See section 4 for more information about adverse reactions.

Columvi contains polysorbates

This medicine contains 1.25 mg of polysorbate 20 in each 2.5 ml vial and 5 mg of polysorbate 20 in each 10 ml vial, equivalent to 0.5 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Columvi

Columvi will be administered under the supervision of a doctor experienced in cancer treatment, in a hospital setting.

Medications administered before treatment with Columvi

• Seven days before starting treatment with Columvi, you will be given another medicine, obinutuzumab, to reduce the number of B-lymphocytes in the blood.

• Between 30 and 60 minutes before receiving Columvi, you may be given other medications (premedication) to help reduce reactions associated with cytokine release syndrome. These medications may include:

• A corticosteroid such as dexamethasone

• A medicine to reduce fever, such as paracetamol

• An antihistamine such as diphenhydramine

How much and how often you will receive Columvi

You may receive up to 12 treatment cycles with Columvi. Each cycle lasts 21 days. During the first two cycles, your doctor will start Columvi treatment with a low dose and gradually increase it to the full dose.

The following is the standard administration schedule:

Cycle 1: includes pre-treatment and 2 low doses of Columvi over the next 21 days:

• Day 1 – pre-treatment with obinutuzumab
• Day 8 – initial dose of 2.5 mg of Columvi
• Day 15 – intermediate dose of 10 mg of Columvi

Cycle 2 to Cycle 12: one dose every 21 days:

• Day 1 – full dose of 30 mg of Columvi

How Columvi is administered and monitoring

Columvi is administered by intravenous infusion (drip into a vein). Your doctor will monitor you during all Columvi infusions and adjust the infusion duration depending on your response to treatment.

• Your first infusion will be given over 4 hours. When Columvi is administered as monotherapy, your doctor will closely monitor you during the first infusion and for 10 hours after it ends. When Columvi is administered in combination with gemcitabine and oxaliplatin, your doctor will closely monitor you during the first infusion and for 4 hours after it ends. This is to monitor for any signs or symptoms of cytokine release syndrome.
• For subsequent infusions, your doctor may monitor you after the infusion ends. This will be necessary if you experienced moderate or severe cytokine release syndrome with your previous dose.
• If you have not experienced cytokine release syndrome after 3 doses, your doctor may administer subsequent infusions over 2 hours.

If you miss a dose of Columvi

If you miss an appointment, reschedule as soon as possible. To ensure the treatment is fully effective, it is very important not to miss any doses.

Before stopping treatment with Columvi

Talk to your doctor before stopping treatment. Stopping treatment may cause your condition to worsen.

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

4. Possible adverse effects

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

Serious adverse effects

Tell your doctor immediately if you experience any of the serious adverse effects listed below – you may require urgent medical treatment.

• Cytokine release syndrome (very common): symptoms may include, among others, fever, rapid heartbeat, feeling of dizziness or lightheadedness, nausea, headache, itching, confusion, chills, and difficulty breathing
• Immune effector cell-associated neurotoxicity syndrome (frequent): symptoms may include, among others, confusion, disorientation, decreased alertness, seizures, or difficulty writing and/or speaking
• Infections (very common): symptoms may include, among others, fever, chills, difficulty breathing, burning sensation when urinating
• Tumour flare (very common): symptoms may include, among others, painful swelling of lymph nodes, chest pain, difficulty breathing easily, or pain in the tumour area
• Tumour lysis syndrome (frequent): symptoms may include, among others, weakness, difficulty breathing, feeling confused, irregular heartbeat, and muscle cramps

Other adverse effects

Tell your doctor or nurse immediately if you notice any of the following adverse effects or if they worsen:

Columvi used alone

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

• decrease in blood levels of:

• neutrophils (a type of white blood cell; neutropenia), which may cause fever or any sign of infection

• red blood cells (anaemia), which may cause tiredness, feeling unwell, and pale skin

• platelets (a type of blood cell; thrombocytopenia), which may cause bruising or bleeding

• fever

• low levels, as determined by blood tests, of phosphate, magnesium, calcium, or potassium

• rash

• constipation

• diarrhoea

• feeling of dizziness (nausea)

• viral infections, such as lung infection, herpes zoster

• headache

Common (may affect up to 1 in 10 people)

• low levels of sodium, measured in blood tests, which may cause tiredness, muscle spasms, or cramps
• increased levels, measured in blood tests, of liver enzymes and bilirubin (a yellow substance in the blood), which may cause yellowing of the skin or eyes, and dark urine
• bacterial infections, such as urinary tract infection, stomach infection or infection around the stomach
• fungal infections (mycosis)
• nose and throat infections (upper respiratory tract infections)
• lung infections such as bronchitis or pneumonia (lower respiratory tract infections), which may cause fever, cough, and difficulty breathing
• blood infection (sepsis), which may cause fever, chills, and confusion
• low levels, as determined by blood tests, of lymphocytes (a type of white blood cell; lymphopenia), which may affect the body’s ability to fight infections
• fever with low neutrophil levels (febrile neutropenia)
• vomiting
• bleeding in the stomach or intestine (gastrointestinal haemorrhage), which may cause black stools or blood in vomit
• confusion
• tremor
• drowsiness

Uncommon (may affect up to 1 in 100 people)

• swelling of the spinal cord (myelitis), which may cause muscle weakness or numbness
• inflammation of the large intestine (colitis), which may cause abdominal pain, bloody stools, and a strong urge to pass stool

Columvi used in combination with anticancer medicines

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

• decrease in blood levels of:

• platelets (a type of blood cell; thrombocytopenia), which may cause bruising or bleeding

• neutrophils (a type of white blood cell; neutropenia), which may cause fever or any symptom of infection

• red blood cells (anaemia), which may cause tiredness, feeling unwell, and pale skin

• lymphocytes (a type of white blood cell; lymphopenia), which may affect the body’s ability to fight infections

• feeling of dizziness (nausea)

• numbness, tingling, burning sensation, pain, discomfort, or weakness and/or difficulty walking (peripheral neuropathy)

• diarrhoea

• increased levels, measured in blood tests, of liver enzymes

• rash

• fever

• vomiting

• muscle and bone pain

• abdominal pain (stomach pain)

• constipation

• low levels in blood tests of potassium (hypokalaemia) or sodium (hyponatraemia)

• infection with COVID-19 caused by a virus called coronavirus (SARS-CoV-2)

• lung infection (pneumonia), which may cause fever, cough, and difficulty breathing

• respiratory tract infections, such as runny nose, sore throat, sinus infections, and chest colds

Common (may affect up to 1 in 10 people)

• headache
• low levels in blood tests of magnesium, calcium, or phosphate
• new or recurrent viral infections, such as herpes and cytomegalovirus infection
• bacterial infections, such as urinary tract infection
• blood infection (sepsis), which may cause fever, chills, and confusion
• fungal infection
• increased levels in blood of: bilirubin, which may cause yellowing of the skin or eyes
• fever with low neutrophil levels (a type of white blood cell)
• inflammation of the large intestine (colitis), which may cause abdominal pain, bloody stools, and a strong urge to pass stool
• inflammation of the pancreas
• inflammation of the lungs (pneumonitis), which may cause cough and difficulty breathing

Uncommon (may affect up to 1 in 100 people)

• tremors
• increased liver enzymes (in clinical tests), which may be a sign of liver inflammation
• lung infection (Pneumocystis jirovecii pneumonia)

If you experience any of the adverse effects listed above or if they worsen, inform your doctor immediately.

Reporting of adverse effects

If you experience any adverse effect, consult 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 Columvi

Your doctor, pharmacist, or nurse is responsible for the storage of this medicine and for the proper disposal of any unused product. This information is intended for healthcare professionals.

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and on the label of the vial after EXP. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (2 °C to 8 °C).
• Do not freeze.
• Keep the vial in the outer packaging to protect it from light.
• Do not use this medicine if it is cloudy, discolored, or contains particles.

Disposal of unused medicine and of all materials that have come into contact with it must be carried out in accordance with local regulations.

6. Contents of the package and other information

Composition of Columvi

• The active substance is glofitamab.
• Columvi 2.5 mg: each vial contains 2.5 milligrams of glofitamab (in 2.5 ml of concentrate) at a concentration of 1 mg/ml.
• Columvi 10 mg: each vial contains 10 milligrams of glofitamab (in 10 ml of concentrate) at a concentration of 1 mg/ml.
• The other components are: L-histidine, L-histidine monohydrochloride monohydrate, L-methionine, sucrose, polysorbate 20 (E432), and water for injections (see section 2 “Columvi contains polysorbates”).

Nature of the product and contents of the container

Columvi concentrate for solution for infusion (sterile concentrate) is a clear, colourless solution supplied in a glass vial.

Each Columvi pack contains one vial.

Marketing Authorisation Holder

Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer

Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Further information on this medicinal product is available from the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this summary:

Other sources of information

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

This information is intended for healthcare professionals only:

The diluted Columvi solution may be administered via intravenous infusion bag (all doses) or via intravenous syringe infusion (only for the 2.5 mg dose).

Columvi must be administered by intravenous infusion through a dedicated infusion line. It must not be given as an intravenous bolus.

The following are instructions for dilution of Columvi prior to administration.

Dilution instructions

• Columvi contains no preservatives and is intended for single use only.
• Prior to intravenous administration, Columvi must be diluted by a healthcare professional using aseptic technique.
• Do not shake the vial. Visually inspect the Columvi vial for particles or discoloration before administration. Columvi is a clear, colourless solution. Discard the vial if the solution is cloudy, discoloured, or contains visible particles.

Preparation of the intravenous infusion bag

• Using a sterile needle and syringe, withdraw the appropriate volume of 9 mg/mL (0.9%) sodium chloride injection solution or 4.5 mg/mL (0.45%) sodium chloride injection solution from the infusion bag as described in Table 1, and discard this solution.
• Using a sterile needle and syringe, withdraw the required volume of Columvi concentrate for the intended dose from the vial and dilute it in the infusion bag (see Table 1 below).

Discard any remaining product in the vial.

• The final concentration of glofitamab after dilution must be between 0.1 and 0.6 mg/mL.
• Gently invert the infusion bag to mix the solution and avoid excessive foaming. Do not shake.
• Inspect the infusion bag for particles and discard if any are present.
• Prior to starting the intravenous infusion, the contents of the infusion bag must be at room temperature (25°C).

Table 1. Dilution of Columvi for intravenous bag infusion

Preparation of the intravenous infusion syringe (for the 2.5 mg dose only)

Use a two-syringe method with a connector to prepare the dose. The final volume of the diluted solution is 25 ml.

• Withdraw 22.5 ml of sodium chloride 9 mg/ml (0.9%) or sodium chloride 4.5 mg/ml (0.45%) injection solution from an infusion bag using a syringe of appropriate size (e.g., 30 ml).
• Using a sterile needle, withdraw 2.5 ml of Columvi concentrate from the vial into a second syringe. Discard any remaining product in the vial.
• Attach a connector to both syringes and transfer the Columvi concentrate into the syringe containing the sodium chloride 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) injection solution. The final concentration of glofitamab after dilution must be 0.1 mg/ml.
• Disconnect the syringes. Introduce air into the syringe containing the diluted Columvi solution and cap it.
• Gently invert the syringe to mix the solution, avoiding excessive foaming. Do not shake.
• Remove air bubbles from the syringe before administration.

Administration

Administer only as intravenous infusion.

Do not administer as rapid intravenous injection or intravenous bolus.

Administer as an intravenous infusion through an infusion line using an intravenous infusion pump or intravenous syringe pump over a maximum of 8 hours.

When the Columvi infusion bag or syringe is empty, ensure that the entire dose of Columvi is administered by flushing the infusion line with an infusion bag or syringe containing sodium chloride 9 mg/ml (0.9%) or sodium chloride 4.5 mg/ml (0.45%) injection solution. Continue infusion at the same rate.

Incompatibilities

Only sodium chloride 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) injection solution should be used to dilute Columvi, as other solvents have not been evaluated.

When diluted with sodium chloride 9 mg/ml (0.9%) injection solution, Columvi is compatible with intravenous infusion bags made of polyvinyl chloride (PVC), polyethylene (PE), polypropylene (PP), or polyolefin. When diluted with sodium chloride 4.5 mg/ml (0.45%) injection solution, Columvi is compatible with intravenous infusion bags made of PVC.

When diluted with sodium chloride 9 mg/ml (0.9%) or 4.5 mg/ml (0.45%) injection solution, Columvi is compatible with syringes composed of PP.

No incompatibilities have been observed with infusion sets having product-contact surfaces made of polyurethane (PUR), PVC, PE polybutadiene (PB), polyetherurethane (PEU), polycarbonate (PC), silicone, polytetrafluoroethylene (PTFE), or acrylonitrile butadiene styrene (ABS), and in-line filter membranes composed of polyethersulfone (PES) or polysulfone. Use of in-line filters with membranes is optional.

Diluted solution for intravenous infusion

Chemical and physical in-use stability has been demonstrated for up to 72 hours at 2–8°C and 24 hours at 30°C, followed by a maximum infusion time of 8 hours.

From a microbiological standpoint, the diluted solution should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours between 2°C and 8°C, unless dilution has been carried out under controlled and validated aseptic conditions.

Disposal

The Columvi vial is for single use only.

Any unused medicine and all materials that have come into contact with it must be disposed of in accordance with local regulations.