Prospect: information for the patient

Columvi 2.5 mg concentrate for solution for infusion

Columvi 10 mg concentrate for solution for infusion

glofitamab

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 may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospectus carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospectus, as you may need to read it again.

• Your doctor will give you a patient information leaflet. Read it carefully and follow the instructions it contains. Always carry this patient information leaflet with you.
• Always show the patient information leaflet to your doctor or nurse or if you visit the hospital.

• If you have any doubts, consult your doctor or nurse.
• If you experience adverse effects, consult your doctor or nurse, even if they are adverse effects that do not appear in this prospectus. See section 4.

What is Columvi

Columvi is a cancer medication that contains the active ingredient glofitamab.

What is Columvi used for

Columvi is used to treat adults with a type of cancer called "large B-cell diffuse lymphoma" (LBDCG). It is used when the cancer:

• has come back (relapse), or
• did not respond to previous treatments.

Large B-cell diffuse lymphoma is a cancer that affects a part of the immune system (the body's defenses).

• Affects a type of white blood cell called "B lymphocytes".
• In LBDCG, B lymphocytes multiply uncontrollably and accumulate in tissues.

How Columvi works

• The active ingredient of 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 lymphocytes, and also to another protein on the surface of T lymphocytes (another type of white blood cell). This activates T lymphocytes and causes them to multiply. This, in turn, leads to the destruction of B lymphocytes, including cancerous cells.

You should not be given Columvi

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

If you are unsure, talk to your doctor or nurse before using Columvi.

Warnings and precautions

Consult your doctor before Columvi is administered if:

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

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

Be aware of severe side effects.

Some side effects of Columvi are severe and potentially life-threatening. These can occur at any time during treatment with Columvi.

Inform your doctor immediatelyif you experience any of the following side effects while receiving Columvi. The symptoms of each side effect are listed in section 4.

• Cytokine release syndrome– is an exaggerated inflammatory disorder associated with medications that stimulate T cells, characterized by fever and deterioration of multiple organs in the body. Cytokine release syndrome is more likely to occur during cycle 1 after administering Columvi (see section 3 "How Columvi is administered"). Close monitoring is required.

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

?Immune effector cell-associated neurotoxicity: effects on the nervous system. Symptoms include feeling confused, disoriented, decreased alertness, seizures, or difficulty writing and/or speaking. Close monitoring is required.

?Tumor lysis syndrome– some people may present with unusual 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 make blood tests to check your condition. Before each infusion, you should be well hydrated and given medications that may help reduce high levels of uric acid. These may help reduce the possible side effects of tumor lysis syndrome.

?Tumor flare– a reaction to certain medications that act on the immune system and appears similar to a worsening of cancer

?Infections– you may have signs of infection, which vary depending on where the infection is located in the body.

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

Your doctor may:

• give you other medications to reduce symptoms and prevent complications,
• interrupt your treatment for a short period of time, or
• interrupt your treatment completely.

Children and adolescents

This medication should 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 medications and Columvi

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

Pregnancy and contraception

• If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor before taking this medication.
• You should not be given Columvi if you are pregnant. This is because Columvi may harm the fetus.
• If you can become pregnant, you should use an effective contraceptive method while being treated with Columvi and for 2 months after the last dose.
• If you become pregnant while being treated with Columvi, inform your doctor immediately.

Breastfeeding

You should not breastfeed while being given Columvi and for 2 months after the last dose. This is because it is not known if Columvi passes into breast milk and may affect the baby.

Driving and using machines

Columvi may affect your ability to drive, ride a bike, or use any tool or machine.

You should not drive, use tools, or use machines 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 (such as feeling confused, disoriented, decreased alertness, seizures, or difficulty writing and/or speaking) and/or symptoms of cytokine release syndrome (such as fever, rapid heartbeat, dizziness or drowsiness, 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 on side effects.

Columvi will be administered under the supervision of an experienced oncologist in a hospital.

Medications administered before treatment with Columvi

• Seven days before starting treatment with Columvi,another medication, obinutuzumab, will be administered to reduce the number of B lymphocytes in the blood.
• Between 30 and 60 minutes before Columvi is administered,other medications (premedication) may be administered to help reduce reactions associated with cytokine release syndrome. These medications may include:

• A corticosteroid such as dexamethasone
• A medication to lower fever, such as paracetamol
• An antihistamine such as diphenhydramine

How much and how often you will receive Columvi

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

Next, the normal administration schedule is indicated.

Cycle 1: will include a 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: only one dose in the next 21 days:

• Day 1 - full dose of 30 mg of Columvi

How Columvi is administered and monitored

Columvi is administered through intravenous infusion. Your doctor will adjust the time needed for the infusion based on how you respond to treatment.

• Your first infusion will be administered over 4 hours. Your doctor will closely monitor you during the first infusion and for the 10 hours following its completion. This is to control any signs or symptoms of cytokine release syndrome.
• For subsequent infusions, your doctor may monitor you after the infusion is completed. This will be necessary if you had a moderate or severe cytokine release syndrome with your previous dose.
• If you do not have any cytokine release syndrome after 3 doses, your doctor may administer subsequent infusions over 2 hours.

What to do if you miss a dose of Columvi

If you miss an appointment, request another as soon as possible. It is very important not to miss any doses for the treatment to be completely effective.

Before interrupting treatment with Columvi

Consult with your doctor before interrupting treatment. Interrupting treatment may worsen your condition.

If you have any other questions about the use of 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

Inform your doctor immediatelyif you experience any of the severe side effects listed below - you may need urgent medical treatment.

?Release of cytokine syndrome (very common):symptoms may include, among others, fever, rapid heart rate, dizziness, nausea, headache, itching, confusion, chills, and difficulty breathing

?Neurotoxicity syndrome associated with immune effector cells (common):symptoms may consist of, among others, confusion, disorientation, decreased alertness, seizures, or difficulty writing and/or speaking?Tumor lysis syndrome (very common):symptoms may include, among others, painful lymph node inflammation, chest pain, difficulty breathing, or pain in the tumor area

?Severe side effects

?Release of cytokine syndrome (very common):symptoms may include, among others, fever, rapid heart rate, dizziness, nausea, headache, itching, confusion, chills, and difficulty breathing

?Neurotoxicity syndrome associated with immune effector cells (common):symptoms may consist of, among others, confusion, disorientation, decreased alertness, seizures, or difficulty writing and/or speaking

?Tumor lysis syndrome (very common):symptoms may include, among others, painful lymph node inflammation, chest pain, difficulty breathing, or pain in the tumor area

Other side effects

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

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

?Decreased levels in the blood of:

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

-red blood cells (anemia), which may cause fatigue, discomfort, and pale skin

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

?fever

?low concentrations, as determined by blood tests, of phosphate, magnesium, calcium, or potassium

?skin rash

?constipation

?diarrhea

?dizziness (nausea)

?viral infections, such as pneumonia, herpes zoster

?headache

Common (may affect up to 1 in 10 people)

?low levels of sodium, as measured by blood tests, which may cause fatigue, muscle spasms, or cramps

?increased levels, as measured by 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 or abdominal infection

?fungus infections

?upper respiratory tract infections (infections of the nose and throat)

?lower respiratory tract infections (pneumonia, bronchitis, or other infections), which may cause fever, cough, and difficulty breathing

?blood infection (septicemia), which may cause fever, chills, and confusion

?low levels, as determined by blood tests, of lymphocytes (a type of white blood cell; lymphopenia)

?fever with low neutrophil levels (neutropenic fever)

?vomiting

?gastrointestinal bleeding (hemorrhage), which may cause black stools or blood in the vomit

?confusion

?shakiness

?drowsiness

Rare (may affect fewer than 1 in 100 people)

?spinal cord swelling (myelitis), which may cause muscle weakness or numbness

If you notice any of the side effects described above or if they worsen, inform your doctor immediately.

Reporting side effects

If you experience any side effects, consult your doctor or nurse. This includes other possible side effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Your doctor, pharmacist, or nurse is responsible for the conservation of this medication and for the proper disposal of unused product. The following information is 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 EXP. The expiration date is the last day of the month indicated.
• Store in refrigerator (2 °C - 8 °C).
• Do not freeze.
• Store the vial in the outer packaging to protect it from light.
• Do not use this medication if it is cloudy, discolored, or contains particles.

The disposal of unused medication and all materials that have been in contact with it will be carried out in accordance with local regulations.

Composition of Columvi

• The active principle 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 hydrochloride monohydrate, L-methionine, sucrose, polisorbate 20 (E432) and water for injection.

Appearance of the product and contents of the pack

Columvi concentrate for solution for infusion (sterile concentrate) is a transparent and colourless solution that is presented in a glass vial.

Each pack of Columvi 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

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country:

Last update of the summary of product characteristics:

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

The European Medicines Agency will review the new information about 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 about this medicinal product is available on the website of the European Medicines Agency:https://www.ema.europa.eu

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This information is intended for healthcare professionals only:

Columvi should be administered by intravenous infusion through a specific infusion line. It should not be administered as a bolus intravenously.

Below are the instructions for diluting Columvi before administration.

Dilution instructions

?Columvi does not contain preservatives and is intended for single use.

?Before intravenous administration, Columvi must be diluted by a healthcare professional using aseptic technique.

?Do not shake the vial. Visually inspect the vial of Columvi to detect particles or discoloration before administration. Columvi is a transparent and colourless solution. Discard the vial if the solution is turbid, has changed colour or contains visible particles.

?Withdraw the required volume of0.9% sodium chloride solution or0.45% sodium chloride solution, as described in Table1, from the infusion bag using a sterile needle and syringe and discard the solution.

?Withdraw the required volume of Columvi concentrate for the planned dose from the vial with a sterile needle and syringe and dilute in the infusion bag (see Table1below). Discard any remaining product in the vial.

?The final concentration of glofitamab after dilution should be 0.1 to 0.6mg/ml.

?Invert the infusion bag gently to mix the solution and prevent excessive foam formation. Do not shake.

?Inspect the infusion bag to discard particles and discard if present.

?Before starting the intravenous infusion, the contents of the infusion bag must be at room temperature (25°C).

Table1. Dilution of Columvi for infusion

Only 0.9% sodium chloride solution or 0.45% sodium chloride solution for injection should be used to dilute Columvi, as other diluents have not been evaluated.

When diluted with 0.9% sodium chloride solution, Columvi is compatible with intravenous infusion bags composed of PVC, PE, PP or PO. When diluted with 0.45% sodium chloride solution, Columvi is compatible with intravenous infusion bags composed of PVC.

No incompatibilities have been observed with infusion equipment with surfaces in contact with the product made of PUR, PVC or PE and in-line filters with membranes made of PES or polysulfone. The use of in-line filters with membranes is optional.

Infusion solution for intravenous infusion

The chemical and physical stability has been demonstrated for use for a maximum of 72hours at 2-8°C and 24hours at 30°C followed by a maximum infusion time of 8hours.

From a microbiological point of view, the diluted solution should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user and normally would not exceed 24hours at 2°C to 8°C, unless the dilution was performed in controlled and validated aseptic conditions.

Disposal

The vial of Columvi is for single use.

The unused medicinal product and all materials that have been in contact with it will be disposed of in accordance with local regulations.