Bavencio (Avelumab)

What Is Bavencio and What Is It Used For?

Bavencio contains the active substance avelumab, a human monoclonal antibody (a type of protein) that binds to a specific target in the body called PD-L1 (programmed death-ligand 1). PD-L1 is found on the surface of certain tumor cells and acts as a shield, protecting them from the immune system's natural defense mechanisms. When avelumab binds to PD-L1, it blocks this protective effect, thereby allowing immune cells (particularly T-cells) to recognize and destroy the cancer cells.

This mechanism of action places Bavencio in the class of drugs known as immune checkpoint inhibitors. Unlike traditional chemotherapy, which directly kills rapidly dividing cells, checkpoint inhibitors work by removing the "brakes" that tumors place on the immune system. This approach has revolutionized cancer treatment over the past decade, offering new hope for patients with previously difficult-to-treat malignancies.

Notably, avelumab is a fully human IgG1 monoclonal antibody that retains the ability to engage antibody-dependent cell-mediated cytotoxicity (ADCC). This means that in addition to blocking the PD-L1/PD-1 interaction, avelumab can also recruit natural killer (NK) cells to directly destroy tumor cells coated with the antibody. This dual mechanism distinguishes avelumab from some other PD-1/PD-L1 inhibitors and may contribute to its overall antitumor activity.

Bavencio is approved for use in adults for the treatment of three distinct cancer types:

• Merkel Cell Carcinoma (MCC): A rare and aggressive form of skin cancer that has metastasized (spread to other parts of the body). MCC is often caused by the Merkel cell polyomavirus or excessive ultraviolet radiation exposure. Bavencio was one of the first immunotherapies approved for this indication and has demonstrated durable responses in clinical trials, including the pivotal JAVELIN Merkel 200 study.
• Urothelial Carcinoma (UC): A form of cancer affecting the urinary tract, including the bladder and upper urinary tract, when it is locally advanced or metastatic. Bavencio is specifically used as maintenance treatment in patients whose disease has not progressed after first-line platinum-based chemotherapy. The landmark JAVELIN Bladder 100 trial demonstrated a significant improvement in overall survival with avelumab maintenance compared to best supportive care alone, establishing a new standard of care in this setting.
• Renal Cell Carcinoma (RCC): A form of kidney cancer that is advanced (has spread beyond the kidney or to other parts of the body). For this indication, Bavencio is used in combination with axitinib (a tyrosine kinase inhibitor) as first-line treatment. This combination targets cancer through two complementary mechanisms: immune activation via PD-L1 blockade and anti-angiogenic activity via VEGF receptor inhibition. The JAVELIN Renal 101 trial demonstrated significant improvements in progression-free survival compared to sunitinib monotherapy.

The decision to use Bavencio is made by a specialist oncologist based on the type and stage of cancer, the patient's overall health status, biomarker expression (such as PD-L1 status), and previous treatment history. Regular monitoring through blood tests, imaging, and clinical assessments is essential throughout the course of treatment to evaluate response and detect potential adverse effects early.

What Should You Know Before Taking Bavencio?

Contraindications

Bavencio must not be used if you are allergic (hypersensitive) to avelumab or to any of the other ingredients in the formulation. The excipients include mannitol, acetic acid, polysorbate 20, sodium hydroxide, and water for injections. If you have a known allergy to polysorbate, inform your doctor, as polysorbate 20 is present in the formulation and may cause allergic reactions in sensitized individuals.

Warnings and Precautions

Before starting Bavencio, your healthcare provider will assess your overall health through a comprehensive evaluation, including blood tests and weight measurements. These assessments will continue throughout your treatment course. It is essential to communicate openly with your medical team about any existing health conditions and any new symptoms that develop during treatment.

Bavencio works by activating your immune system, which means it can potentially cause inflammation in virtually any part of the body. These immune-mediated adverse reactions can range from mild to life-threatening and may include:

• Infusion-related reactions – symptoms such as shortness of breath, chills, fever, flushing, low blood pressure, back pain, or abdominal pain during or shortly after the infusion
• Pneumonitis – inflammation of the lungs causing cough, breathing difficulties, or chest pain
• Hepatitis – inflammation of the liver, potentially causing jaundice, dark urine, nausea, or abnormal liver function tests
• Colitis – inflammation of the intestines causing diarrhea, bloody stools, or abdominal pain
• Pancreatitis – inflammation of the pancreas causing abdominal pain, nausea, and vomiting
• Myocarditis – inflammation of the heart muscle causing chest pain, shortness of breath, or irregular heartbeat
• Endocrinopathies – disorders of hormone-producing glands including the thyroid, adrenal glands, and pituitary gland, which can affect how these glands function
• Type 1 diabetes – including potentially life-threatening diabetic ketoacidosis, with symptoms such as increased hunger or thirst, frequent urination, weight loss, and fruity-smelling breath
• Nephritis – inflammation of the kidneys, which may present as decreased urine output, blood in urine, or swollen ankles
• Myositis and polymyalgia rheumatica – inflammation of the muscles causing pain, weakness, or stiffness
• Sarcoidosis – inflammatory condition affecting lungs, skin, eyes, or lymph nodes
• Sclerosing cholangitis – inflammation and scarring of the bile ducts, which may cause upper abdominal pain, liver or spleen swelling, fatigue, itching, or jaundice
• Arthritis – inflammation of the joints causing pain, stiffness, and swelling
• Sjögren's syndrome – inflammation of glands that produce moisture, resulting in dry eyes and dry mouth
• Gastritis – inflammation of the stomach lining causing abdominal pain or nausea

Inform your doctor before receiving Bavencio if you have any of the following conditions:

• An autoimmune disease (a condition where the body attacks its own cells), as Bavencio may worsen or trigger flares of autoimmune conditions
• HIV infection or AIDS
• A current or history of chronic viral liver infection, including hepatitis B (HBV) or hepatitis C (HCV)
• You are taking immunosuppressive medications
• You have had an organ transplant, as immune checkpoint inhibitors may increase the risk of organ rejection

Patients who already have an autoimmune disease may experience frequent flares while on Bavencio, although most of these tend to be mild and manageable with appropriate medical support.

Pregnancy and Breastfeeding

Bavencio may cause harm to an unborn baby. Based on its mechanism of action, avelumab can disrupt the PD-L1/PD-1 pathway, which plays an important role in maintaining immune tolerance during pregnancy. Animal studies with other PD-1/PD-L1 inhibitors have shown increased rates of pregnancy loss and adverse developmental effects. If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine.

Do not use Bavencio during pregnancy unless your physician explicitly recommends it after carefully weighing the potential benefits against the risks to the fetus. Women of childbearing potential must use effective contraception during treatment and for at least 1 month after the last dose.

Do not breastfeed during treatment with Bavencio and for at least 1 month after the last dose. It is not known whether avelumab passes into breast milk, and a risk to the newborn or infant cannot be excluded. Human immunoglobulin G (IgG) antibodies are known to be present in breast milk, so exposure of the infant to avelumab through breastfeeding is possible.

Children and Adolescents

Bavencio has not been studied in children and adolescents under 18 years of age. The safety and efficacy of avelumab in the pediatric population have not been established. Therefore, Bavencio should not be used in patients under 18 years of age.

Driving and Operating Machinery

Do not drive or operate machinery after receiving Bavencio if you do not feel well enough. Fatigue is a very common side effect of this medication and may impair your ability to drive safely or use machinery effectively. If you experience significant tiredness, dizziness, or any other symptom that affects your alertness, refrain from driving until these symptoms resolve.

Sodium and Polysorbate Content

Bavencio contains less than 1 mmol (23 mg) sodium per 200 mg dose, making it essentially sodium-free. However, it contains 5 mg polysorbate 20 per vial. Polysorbates may cause allergic reactions in some individuals. Inform your doctor if you have any known allergies to polysorbates.

How Does Bavencio Interact with Other Drugs?

As a monoclonal antibody, avelumab is not metabolized by cytochrome P450 enzymes and is therefore not expected to have traditional pharmacokinetic drug-drug interactions. However, because of its immunological mechanism of action, several important pharmacodynamic considerations apply when Bavencio is used concurrently with other medications.

Always inform your healthcare provider about all medications you are currently taking, have recently taken, or may plan to take. This includes prescription drugs, over-the-counter medicines, herbal supplements, and vitamins. In particular, the following interactions are clinically relevant:

Because Bavencio modifies the immune system, it is important to consider the potential for additive immunological effects when used alongside other immune-modifying therapies. Patients who are taking medications for autoimmune conditions should be closely monitored, as Bavencio may exacerbate underlying autoimmune disorders or reduce the efficacy of immunosuppressive therapy.

For patients receiving the Bavencio plus axitinib combination for renal cell carcinoma, it is important to also review the drug interaction profile of axitinib. Axitinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, grapefruit juice) may increase axitinib plasma concentrations, while strong CYP3A4 inducers (e.g., rifampin, phenytoin, St. John's wort) may decrease its efficacy.

What Is the Correct Dosage of Bavencio?

Bavencio is always administered in a hospital or clinic setting under the supervision of an experienced oncologist. The medication is given as an intravenous infusion (drip into a vein) over a period of approximately 1 hour. Before administration, the concentrated solution from the vial is diluted in a sodium chloride infusion bag (either 0.9% or 0.45% NaCl solution, preferably 250 mL).

Adults

Unlike some oncology medications, Bavencio uses a fixed-dose regimen rather than weight-based dosing. This simplifies preparation and reduces dosing errors. The flat dose of 800 mg was selected based on pharmacokinetic modeling that demonstrated comparable drug exposure across a wide range of body weights.

Premedication

To reduce the risk of infusion-related reactions, patients must receive premedication before Bavencio administration:

• Paracetamol (acetaminophen) and an antihistamine before at least the first four infusions
• Depending on your body's response, the treating physician may decide to continue premedication before all subsequent infusions

Renal Cell Carcinoma (Combination Therapy)

Children

Bavencio is not approved for use in children and adolescents under 18 years of age. Safety and efficacy have not been established in this population.

Elderly

No dose adjustment is required for elderly patients. Clinical trials included patients over 65 years of age, and no overall differences in safety or efficacy were observed compared to younger adults. However, as with any cancer treatment, individual assessment of fitness and comorbidities is essential to guide treatment decisions.

Missed Dose

It is very important to attend all scheduled appointments for your Bavencio infusions. If you miss an appointment, contact your healthcare team as soon as possible to reschedule. The next dose should be administered as soon as feasible; do not wait until the next regularly scheduled dose if a prompt rescheduling is possible.

Dose Modifications and Discontinuation

Your oncologist may need to delay or permanently discontinue Bavencio treatment based on the severity of side effects, particularly immune-mediated adverse reactions. Dose reductions are generally not recommended for Bavencio; instead, treatment is either withheld temporarily or discontinued permanently. Common reasons for treatment modification include:

• Grade 2 or higher immune-mediated adverse reactions (treatment may be withheld until symptoms resolve to Grade 1 or less)
• Grade 3 or 4 adverse reactions (treatment may be permanently discontinued depending on the organ system affected)
• Requirement for high-dose systemic corticosteroids (prednisone ≥10 mg/day or equivalent) for more than 12 weeks
• Recurrent Grade 3 or Grade 4 immune-mediated adverse reactions
• Grade 3 or 4 infusion-related reactions

Do not stop treatment with Bavencio without first discussing it with your doctor, as discontinuing therapy may allow the cancer to progress.

Overdose

Since Bavencio is administered by healthcare professionals in a controlled setting, overdose is unlikely. In clinical trials, doses up to 20 mg/kg have been administered without identification of a maximum tolerated dose. In case of suspected overdose, the patient should be closely monitored for signs of adverse reactions, and appropriate supportive treatment should be initiated. There is no specific antidote for avelumab.

What Are the Side Effects of Bavencio?

Like all medicines, Bavencio can cause side effects, although not everybody experiences them. Because Bavencio activates the immune system, it can cause inflammation in various parts of the body. Some of these immune-mediated reactions can be serious or life-threatening and may require treatment with corticosteroids or other immunosuppressive agents.

Importantly, some side effects may appear weeks or months after your last dose. It is crucial to report any new or worsening symptoms to your healthcare team, even if they seem unrelated to your cancer treatment. Do not attempt to treat these symptoms on your own with other medications.

Bavencio Monotherapy (Single-Agent Use)

The following side effects have been reported in clinical trials with avelumab used alone (for MCC and UC maintenance):

Bavencio + Axitinib Combination (for RCC)

When Bavencio is used in combination with axitinib for renal cell carcinoma, the side effect profile differs from monotherapy. The combination may produce additional or more frequent adverse effects due to the overlapping toxicity profiles of both agents. The following have been observed in clinical trials:

Additional side effects reported with other similar checkpoint inhibitor medicines (class effects) include exocrine pancreatic insufficiency (decreased production of digestive enzymes by the pancreas) and celiac disease (gluten intolerance with symptoms of abdominal pain, diarrhea, and bloating after eating gluten-containing foods). While these have not been specifically confirmed with Bavencio monotherapy, patients and healthcare providers should remain vigilant for these potential class effects.

How Should You Store Bavencio?

Since Bavencio is administered in a hospital or clinic setting, storage is managed by healthcare professionals. However, patients and caregivers should be aware of the following storage requirements:

• Temperature: Store in a refrigerator at 2°C to 8°C (36°F to 46°F)
• Freezing: Do not freeze the concentrate. Do not shake the diluted solution.
• Light protection: Store in the original carton to protect from light
• Shelf life: Do not use after the expiry date printed on the vial label and carton (the expiry date refers to the last day of that month)
• Diluted solution: The diluted infusion solution should be used immediately after preparation. If not used immediately, it should be stored in a refrigerator and allowed to reach room temperature (20°C to 25°C) before administration.
• Disposal: Do not save any unused concentrate or diluted infusion solution for later use. Any unused medicine or waste material should be disposed of in accordance with local regulations.

Keep all medicines out of the sight and reach of children. The healthcare facility where you receive your infusion is responsible for proper storage, aseptic preparation, and disposal of Bavencio.

What Does Bavencio Contain?

Active Ingredient

The active substance is avelumab. Each 10 mL vial contains 200 mg of avelumab, corresponding to a concentration of 20 mg per mL of concentrate.

Inactive Ingredients (Excipients)

Appearance and Packaging

Bavencio concentrate for solution for infusion is a clear, colorless to slightly yellow solution. It should be visually inspected before use; discard the vial if the solution is cloudy, discolored, or contains visible particles. The concentrate is supplied in a Type I glass vial with a rubber stopper and aluminum seal with a flip-off cap. Each carton contains 1 vial of 10 mL concentrate (200 mg avelumab).

Marketing Authorization Holder and Manufacturer

Bavencio is manufactured by Merck Serono S.p.A. in Modugno (Bari), Italy, and marketed by Merck Europe B.V. (Amsterdam, Netherlands) in partnership with Pfizer. The product is approved by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), among other regulatory authorities worldwide. The drug was first approved by the FDA in March 2017 for metastatic Merkel cell carcinoma, marking an important milestone in the treatment of this rare cancer.