Metastatic Merkel Cell Carcinoma (MCC):
Treatment of adults and pediatric patients aged 12 years and above with metastatic Merkel cell carcinoma.

Locally Advanced or Metastatic Urothelial Carcinoma (UC):

• First-line maintenance therapy: For patients with locally advanced or metastatic urothelial carcinoma whose disease has not progressed following first-line platinum-based chemotherapy.

Previously treated urothelial carcinoma:

• For patients with locally advanced or metastatic urothelial carcinoma who have experienced disease progression during or after platinum-based chemotherapy,
• or within 12 months after neoadjuvant or adjuvant platinum-containing therapy.

Advanced Renal Cell Carcinoma (RCC): In combination with axitinib for first-line treatment of patients with advanced renal cell carcinoma.

PD-L1 is expressed on tumor cells and tumor-infiltrating immune cells and plays a role in suppressing the body’s anti-tumor immune response. Interaction of PD-L1 with PD-1 and B7.1 receptors on T-cells and antigen-presenting cells inhibits T-cell activation, proliferation, and cytokine production. Avelumab binds to PD-L1 and blocks its interaction with PD-1 and B7.1 receptors, thereby removing immune suppression and restoring T-cell–mediated anti-tumor activity. Additionally, Avelumab can induce antibody-dependent cell-mediated cytotoxicity (ADCC), contributing to tumor cell destruction. Preclinical studies have demonstrated reduced tumor growth when PD-L1 activity is inhibited.

Premedication: Premedicate patients with an antihistamine and with acetaminophen prior to the first 4 infusions of Avelumab. Premedication should be administered for subsequent Avelumab doses based upon clinical judgment and presence/severity of prior infusion reactions.

Recommended Dosage for MCC: The recommended dosage of Avelumab is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

Recommended Dosage for UC: The recommended dosage of Avelumab is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

Recommended Dosage for RCC: The recommended dosage of Avelumab is 800 mg administered as an intravenous infusion over 60 minutes every 2 weeks in combination with axitinib 5 mg orally taken twice daily (12 hours apart) with or without food until disease progression or unacceptable toxicity. When axitinib is used in combination with Avelumab, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of two weeks or longer.

Avelumab may cause the following clinically significant adverse reactions:

• Severe or life-threatening immune-mediated reactions affecting various organs
• Infusion-related reactions
• Complications associated with allogeneic hematopoietic stem cell transplantation (HSCT)
• Major cardiovascular adverse events

Based on its mechanism of action, Avelumab may cause fetal harm when administered during pregnancy. There are no adequate data in pregnant women, but animal studies suggest that inhibition of the PD-1/PD-L1 pathway may lead to immune-mediated fetal rejection and fetal death. Human IgG1 antibodies can cross the placenta; therefore, Avelumab may be transferred to the fetus. Patients should be informed about the potential risk if used during pregnancy.

There are no data regarding the presence of Avelumab in human milk or its effects on breastfed infants. Due to the potential for serious adverse reactions, breastfeeding is not recommended during treatment and for at least one month after the last dose.

Immune-mediated adverse reactions:

• Avelumab may cause immune-mediated adverse reactions that can be severe or life-threatening and may affect any organ system. These include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal impairment, and dermatologic reactions. It may also lead to rejection in patients with solid organ transplants.
• Patients should be closely monitored for early detection and management. Liver enzymes, serum creatinine, and thyroid function should be assessed at baseline and periodically during therapy. Treatment should be withheld or permanently discontinued depending on the severity and type of reaction.

Infusion-related reactions: Infusion-related reactions may occur and should be managed by slowing, interrupting, or permanently discontinuing the infusion based on severity.

Complications of allogeneic HSCT: Serious and potentially fatal complications may occur in patients receiving allogeneic hematopoietic stem cell transplantation before or after treatment with PD-1/PD-L1 inhibitors.

Major adverse cardiovascular events: Cardiovascular risk factors should be appropriately managed. In cases of severe (Grade 3–4) events, particularly when used with axitinib, treatment should be discontinued.

Embryo-fetal toxicity: Avelumab may cause harm to the fetus. Women of reproductive potential should be informed of the risks and advised to use effective contraception during treatment.

Pediatric Use: Safety and effectiveness have been established in patients aged 12 years and older for metastatic Merkel cell carcinoma. Clinical data suggest similar exposure and response between adults and pediatric patients in this age group.

Store below 25°C, protected from light and moisture. Keep out of reach of children.