Prescribing Information for the Patient

Bavencio 20 mg/ml Concentrate for Solution for Infusion

avelumab

Read this entire prescribing information carefully before starting to use this medicine, as it contains important information for you.

• Keep this prescribing information, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this prescribing information. See section 4.

Bavencio contains the active ingredient avelumab, a monoclonal antibody (a type of protein) that binds to a specific target in the body called PD-L1.

PD-L1 is found on the surface of certain tumor cells and helps to protect them from the immune system (the body's natural defenses). Bavencio binds to PD-L1 and blocks this protective effect, allowing the immune system to attack the tumor cells.

Bavencio is used in adults to treat:

• Merkel cell carcinoma (MCC), a rare type of skin cancer, when it is metastatic (has spread to other parts of the body).
• Urothelial carcinoma (UC),a cancer that originates in the urinary tract, when it is advanced or metastatic (has spread beyond the bladder or to other parts of the body). Bavencio is used as maintenance treatment if the tumor has not grown after platinum-based chemotherapy as first-line treatment.
• Renal cell carcinoma (RCC), a type of kidney cancer, when it is advanced (has spread beyond the kidney or to other parts of the body).

For renal cell carcinoma, Bavencio must be used in combination with axitinib.

It is essential that you also read the medication prospect that contains axitinib and consult your doctor if you have any doubts.

No use Bavencio

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

Warnings and Precautions

Blood tests and weight controls

Your doctor will check your overall health before and during treatment with Bavencio.

Blood tests will be performed during treatment, and your doctor will monitor your weight before and during treatment.

Consult your doctor before starting Bavencio

Bavencio may cause side effects (see section 4). Note that these symptoms sometimes occur late and may appear after the last dose. If you experience any of them, you mustseekurgent medical attention:

• reactions associated with infusion;
• problems due to inflammation of your lungs (pneumonitis);
• inflammation of your liver (hepatitis) or other liver problems;
• inflammation of your intestines (colitis), diarrhea (loose, watery, or soft stools) or more frequent bowel movements;
• inflammation of your pancreas (pancreatitis);
• inflammation of your heart (myocarditis);
• problems with hormone-producing glands (the thyroid gland, adrenal glands, and pituitary gland) that may affect your functioning;
• type 1 diabetes, including a serious, sometimes potentially life-threatening condition due to the presence of acid in the blood caused by diabetes (diabetic ketoacidosis);
• problems with your kidneys;
• inflammation of your muscles (myositis and polymyalgia rheumatica);
• problems due to inflammation of your lungs, skin, eyes, or lymph nodes (sarcoidosis);
• inflammation and fibrosis of the bile ducts (primary biliary cirrhosis);
• inflammation of your joints (arthritis);
• inflammation of glands that produce secretions that moisten the body (Sjögren's syndrome).

If you notice any of these symptoms while taking Bavencio,do nottry to treat them on your own with other medications. Your doctor may

• administer other medications to prevent complications and reduce symptoms,
• postpone the next dose of Bavencio,
• or discontinue treatment with Bavencio permanently.

Consult your doctor or nurse before starting Bavencio if

• you have an autoimmune disease (a disorder in which the body attacks its own cells);

• you have a human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS);
• you have or have had a chronic viral hepatitis infection, including hepatitis B (HBV) or hepatitis C (HCV);
• you are receiving immunosuppressive medications;
• you have undergone an organ transplant.

Bavencio acts on the immune system and may cause inflammation in some parts of your body. The risk of experiencing these side effects may be higher if you already have an autoimmune disease (a disorder in which the body attacks its own cells). You may also experience frequent relapses of your autoimmune disease, which in most cases will be mild.

Children and adolescents

Bavencio has not been studied in children and adolescents under 18 years of age. Therefore, Bavencio should not be used in children and adolescents under 18 years of age.

Other medications and Bavencio

Inform your doctor if you are taking, have taken recently, or may need to take any other medication.

Pregnancy

Bavencio may cause harm to the fetus. If you are pregnant, think you may be pregnant, or intend to become pregnant, consult your doctor before using this medication.

You should not use Bavencio if you are pregnant unless your doctor recommends it specifically.

If you are a woman who may become pregnant, you must use effective contraceptive methods while receiving treatment with Bavencio and for at least 1 month after the last dose.

Lactation

Inform your doctor if you are breastfeeding.

Do notbreastfeed while receiving Bavencio and for at least 1 month after the lastdose.

The passage of Bavencio into breast milk is unknown. The risk in the infant cannot be ruled out.

Driving and operating machinery

Do notdrive or operate machinery after receiving Bavencio if you are not feeling well enough. Fatigue is a very common side effect of Bavencio and may affect your ability to drive or operate machinery.

Bavencio has a low sodium content

Bavencio contains less than 1 mmol of sodium (23 mg) per 200 mg dose; this is essentially "sodium-free".

You will receive Bavencio in a hospital or clinic under the supervision of an experienced doctor.

How Much Bavencio You Will Receive

The recommended dose of avelumab is 800 mg every 2 weeks. Your doctor will decide how many treatments you need.

How You Will Receive Bavencio

You will receive Bavencio as an infusion (IV) through a vein over a period of 1 hour. Bavencio will be added to a solution of sodium chloride before use.

Before Receiving Bavencio

During at least the first 4 treatments, you will receive paracetamol and an antihistamine before Bavencio is administered to help prevent possible infusion-related adverse effects. Depending on how your body responds to the treatment, your doctor may decide to continue giving you these medications before all Bavencio treatments.

If You Miss a Dose of Bavencio

It is very important that you attend all scheduled appointments to receive Bavencio. If you miss an appointment, ask your doctor when to schedule the next dose.

If You Interrupt Treatment with Bavencio

Nointerrupt treatment with Bavencio unless you have discussed it with your doctor.

Interrupting treatment may stop the medication's effect.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Some side effects may appear weeks or months after the last dose.

Bavencio acts on the immune system and can cause inflammation in some parts of the body (see section 2). Inflammation can cause serious damage to the body and some inflammatory disorders can put your life at risk and require treatment or suspension of Bavencio.

Seek urgent medical attention if you notice inflammation in any part of your bodyor if you experienceany of the following signs or symptoms, or if they worsen.

• Signs of reactions associated with infusion such asshortness of breath or wheezing (sounds when breathing), chills or shivering, swollen or itchy skin, redness, low blood pressure(dizziness, fatigue, nausea), fever, back painandabdominal pain. Thesereactions are very common.

• Signs of inflammation of hormone-producing glands, which can affect your function, may includeextreme fatigue, rapid heartbeat, increased sweating, changes in mood or behavior,such as irritability orfrequent forgetfulness,feeling cold, very low blood pressure (blackouts, dizziness, fatigue, nausea),weight changesorheadache. These reactions are very common for the thyroid gland, common for the adrenal glands and rare for the pituitary gland.

• Signs of lung inflammation (pneumonitis) may bedifficulty breathingorcoughing. These reactions are common.

• Between the signs of intestinal inflammation (colitis) may bediarrhea(soft stools) ormore frequent bowel movements,blood in the stool or dark, tar-like stoolsorintense abdominal painorsensitivity to palpation in the abdominal area. These reactions are common.

• Between the signs of liver problems, including liver inflammation (hepatitis), may beyellowing of the skin(jaundice) or of thewhite part of the eyes,nausea or intense vomiting, pain in the right upper abdominal area(abdomen), drowsiness, dark urine(tea-colored), bleeding or bruising more easily than normal, less hunger than usual, fatigueorabnormal liver function tests. These reactions are common.

• Signs of pancreatitis inflammation may includeabdominal pain,nauseaandvomiting. These reactions are rare.

• Signs of heart inflammation (myocarditis) may includedifficulty breathing,dizzinessorblackouts, fever, painandchest tightnessorsymptoms similar to the flu. These reactions are rare.

• Signs of type 1 diabetes, including diabetic ketoacidosis, may includeincreased hungerorthirst,needing to urinate more frequently, weight lossandfeeling tiredorhaving difficulty thinking clearly, breath with a sweet or fruity odororfeeling sickorbeing sick, abdominal painanddeep or rapid breathing. Thesereactions are rare.

• Signs of kidney inflammation may includeabnormal kidney function tests, urinating less than usual, blood in the urineorswelling of the ankles. Thesereactions are rare.

• Signs of muscle inflammationsuch asmyositis,whichmay includemuscle painorweaknessin the muscles,and polymyalgia rheumatica, which may includemuscle painorstiffness in the muscles. Myositis is rare and the frequency of polymyalgia rheumatica is unknown.

• Signs of inflammation associated withan accumulation of inflammatory cellsin various organs and tissues, more frequently in the lungs (sarcoidosis). These reactions are rare.

• Signs of joint inflammation (arthritis), which may includepain,stiffnessandswellingin the joints. These are rare.

• Signs of inflammation and fibrosis of the bile ducts, which may includepain in the upper right abdominal area,swelling of the liver or spleen, fatigue, itchingoryellowing of the skin or the white part of the eyes(primary biliary cirrhosis). The frequency is unknown.

• Signs of inflammation of the glands thatproduce secretions that moisten the body, such as tears and saliva, which may includedry eyesanddry mouth(Sjögren's syndrome). The frequency is unknown.

Do not try to treat them on your own with other medications.

Other side effects

Some side effects may not produce symptoms and can only be discovered through blood tests.

In clinical studies with avelumab alone, the following side effects have been reported:

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

• Low red blood cell count
• Nausea, loose stools, constipation, vomiting
• Abdominal pain, back pain, joint pain
• Cough, difficulty breathing
• Feeling tired or weak
• Fever
• Swelling of the arms, legs, or feet
• Weight loss, decreased appetite

Common (may affect up to 1 in 10 people)

• Decreased white blood cell count (lymphocytes)
• Decreased platelet count in the blood
• Increased blood pressure
• Low sodium levels
• Headache, dizziness
• Feeling cold
• Dry mouth
• Elevated liver enzymes in the blood
• Elevated pancreatic enzymes in the blood
• Rash, itching
• Muscle pain
• Illness similar to the flu (includes feeling feverish and muscle pains)
• Numbness, tingling, weakness, burning sensation in the arms or legs

Rare (may affect up to 1 in 100 people)

• Redness of the skin
• Intestinal obstruction
• Rash, pruritic, scaly skin, dry skin
• Low blood pressure
• Elevated muscle enzymes in the blood
• Increased white blood cell count (eosinophils)
• Arthritis (rheumatoid arthritis)
• Myasthenia gravis, myasthenic syndrome, a disease that can cause muscle weakness

Very rare (may affect up to 1 in 1,000 people)

• Urinary tract inflammation. The signs and symptoms may include frequent or painful urination, urgent need to urinate, blood in the urine, pain or pressure in the lower abdominal area

In clinical studies with avelumab in combination with axitinib, the following side effects have been reported:

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

• Loose stools, nausea, constipation, vomiting
• Increased blood pressure
• Feeling tired or weak
• Hoarseness, cough, difficulty breathing
• Decreased appetite, weight loss
• Headache, dizziness
• Abdominal pain, back pain, joint pain, muscle pain
• Elevated liver enzymes in the blood
• Feeling cold
• Rash, itching
• Fever

Common (may affect up to 1 in 10 people)

• Rash, pruritic, scaly skin, acne-like rash
• Swelling of the arms, legs, or feet
• Dry mouth
• Elevated pancreatic enzymes in the blood
• Decreased kidney function
• Decreased red blood cell count
• Low blood pressure
• Elevated blood sugar levels
• Illness similar to the flu (includes feeling feverish and muscle pains)
• Elevated muscle enzymes in the blood
• Decreased platelet count in the blood
• Numbness, tingling, weakness, burning sensation in the arms or legs
• Redness of the skin

Rare (may affect up to 1 in 100 people)

• Decreased white blood cell count (lymphocytes)
• Increased white blood cell count (eosinophils)
• Intestinal obstruction
• Myasthenia gravis, myasthenic syndrome, a disease that can cause muscle weakness

With other similar medications, the following side effects have been reported:

• Pancreatic insufficiency (exocrine)
• Celiac disease (characterized by symptoms such as abdominal pain, diarrhea, and bloating after consuming gluten-containing foods)

Reporting of side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

Store in refrigerator (between 2 °C and 8 °C).

Do not freeze.

Store in the original packaging to protect it from light.

Do not store any unused portion of the concentrate or diluted infusion solution for re-use.

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 Bavencio

The active ingredient is avelumab.

One vial of 10 ml contains 200 mg of avelumab. Each ml of concentrate contains 20 mg of avelumab.

The other components are: mannitol, glacial acetic acid, polisorbate 20, sodium hydroxide, and water for injection (see section 2 “Bavencio has a low sodium content”).

Appearance of the product and contents of the pack

Bavencio is a sterile concentrate for solution for infusion (sterile concentrate) transparent, colorless to slightly yellow.

The pack size is 1 vial of glass per box.

Marketing Authorization Holder

Merck Europe B.V.

Gustav Mahlerplein 102

1082 MA Amsterdam

Netherlands

Responsible for manufacturing

Merck Serono S.p.A.

Via Delle Magnolie 15 (loc. frazione Zona Industriale)

70026 - Modugno (BA)

Italy

Last review date of this leaflet:

02/2025

Other sources of information

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

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This information is intended solely for healthcare professionals:

Handling instructions

Preparation and administration

Aseptic technique must be used for the preparation of the infusion solution.

• The vial must be visually inspected for particles and color changes. Bavencio is a transparent, colorless to slightly yellow solution. If the solution is turbid, has changed color, or contains particles, the vial must be discarded.
• A suitable infusion bag (preferably 250 ml) containing a sodium chloride solution for infusion of 9 mg/ml (0.9%) or a sodium chloride solution for infusion of 4.5 mg/ml (0.45%) must be used. The required volume of Bavencio must be withdrawn from (from) the vial(s) and transferred to the infusion bag. Any partially used or empty vial must be discarded.
• The diluted solution must be mixed by gently inverting the bag to avoid foam formation or excessive shearing of the solution.
• The solution must be inspected to ensure it is transparent, colorless, and free of visible particles. The diluted solution must be used immediately after preparation.
• Do not administer other medications through the same intravenous route. Administer the infusion using a sterile, pyrogen-free, and low-protein binding filter or accessory with a pore size of 0.2 microns.

After administration of Bavencio, the infusion site must be flushed with a sodium chloride solution for infusion of 9 mg/ml (0.9%) or a sodium chloride solution for infusion of 4.5 mg/ml (0.45%).

Do not freeze or shake the diluted solution. If refrigerated, the diluted solution in the intravenous bags must be allowed to reach room temperature (between 20 °C and 25 °C) before use.

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