Avelumab

Avelumab is used for: Monotherapy for metastatic Merkel cell carcinoma (MCC).

Merkel Cell Carcinoma Indicated in adults with metastatic Merkel cell carcinoma (MCC) 800 mg IV q2Weeks Continue until disease progression or unacceptable toxicity Urothelial Carcinoma Indicated for locally advanced or metastatic urothelial carcinoma (UC) in patients who have disease progression during or following platinum-containing chemotherapy or disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy 800 mg IV q2Weeks Continue until disease progression or unacceptable toxicity

Merkel Cell Carcinoma Indicated for metastatic Merkel cell carcinoma (MCC) in adults and pediatric patients aged >12 yr <12 years: Safety and efficacy not established >12 years: 800 mg IV q2Weeks Continue until disease progression or unacceptable toxicity

IV Preparation Visually inspect vial for particulate matter and discoloration; should appear as a clear, colorless to slightly yellow solution Discard vial if solution is cloudy, discolored, or contains particulate matter Withdraw required dosage volume and inject it into a 250-mL infusion bag containing either 0.9% or 0.45% NaCl Gently invert bag to mix diluted solution and avoid foaming or excessive shearing Inspect admixture solution to ensure it is clear, colorless, and free of visible particles Discard any partially used or empty vials IV Administration Infuse IV over 60 minutes through an IV line containing a sterile, nonpyrogenic, low protein-binding inline filter (pore size of 0.2 micron) Do not coadminister other drugs through the same IV line Premedication Premedicate with an antihistamine and acetaminophen before the first 4 infusions Based clinical judgment, premedicate for subsequent doses and presence/severity of prior infusion reactions

Monitor patients for signs & symptoms of infusion-related reactions. Stop treatment if Grade 3 or 4 infusion-related reactions occur. For Grade 1 infusion-related reactions, decrease infusion rate by 50%. For Grade 2 infusion-related reactions, temporary discontinue infusion until Grade 1 or resolved, then restart infusion w/ 50% slower infusion rate. Risk of immune-related adverse reactions (reversible & can be managed by discontinuation, administration of corticosteroids &/or supportive care). Monitor for signs & symptoms of immune-related pneumonitis, & rule out causes other than immune-related pneumonitis. Administer corticosteroids for Grade >2 events. Withhold treatment for Grade 2 immune-related pneumonitis until resolution, & permanently discontinue for Grade 3, Grade 4 or recurrent Grade 2 immune-related pneumonitis. Monitor for changes in liver function & symptoms of immune-related hepatitis, & rule out causes other than immune-related hepatitis. Administer corticosteroids for Grade >2 events. Withhold treatment for Grade 2 immune-related hepatitis until resolution, & permanently discontinue for Grade 3 or 4 immune-related hepatitis. Monitor for signs & symptoms of immune-related colitis & rule out causes other than immune-related colitis. Administer corticosteroids for Grade >2 events. Withhold treatment for Grade 2 or 3 immune-related colitis until resolution & permanently discontinue for Grade 4 or recurrent Grade 3 immune-related colitis. Risk of immune-related thyroid disorders, immune-related adrenal insufficiency, & type 1 DM. Monitor for clinical signs & symptoms of endocrinopathies. Withhold treatment for Grade 3 or 4 endocrinopathies until resolution. Can cause immune-related nephritis. Monitor for elevated serum creatinine prior to & periodically during treatment. Administer corticosteroids for Grade >2 nephritis. Withhold treatment for Grade 2 or 3 nephritis until resolution to Grade ≤1 & permanently discontinue for Grade 4 nephritis. Reports of myocarditis including fatal cases, myositis, hypopituitarism, uveitis, & Guillain-Barre syndrome. For suspected immune-related adverse reactions, ensure adequate evaluation to confirm aetiology or to rule out other causes. Based on the severity, withhold treatment & administer corticosteroids. Resume treatment when immune-related adverse reaction returns to Grade <1 following corticosteroid taper. Permanently discontinue for any recurrent Grade 3 immune-related adverse reaction & for Grade 4 immune-related adverse reaction. Lactation Unknown if distributed in human breast milk Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose owing to the potential for serious adverse reactions in breastfed infants

Pregnancy Based on its mechanism of action, fetal harm may occur when administered to a pregnant woman Animal studies demonstrated that PD-1/PD-L1 pathway inhibition can lead to increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death Human IgG1 immunoglobulins (IgG1) are known to cross the placenta; therefore, transmission may potentially occur from the mother to the developing fetus Advise patient of the potential risk to a fetus Contraception Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose Lactation Unknown if distributed in human breast milk Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose, owing to the potential for serious adverse reactions in breastfed infants

Side effects of Avelumab : >10% Fatigue (50%) Musculoskeletal pain (32%) Diarrhea (23%) Nausea (22%) Infusion-related reaction (22%) Rash (22%) Peripheral edema (20%) Decreased appetite (20%) Cough (18%) Constipation (17%) Abdominal pain (16%) Arthralgia (16%) Decreased weight (15%) Dizziness (14%) Vomiting (13%) Hypertension (13%) Dyspnea (11%) 1-10% Pruritus (10%) Headache (10%) Thyroid disorders (6%) Hypertension, Grade 3 or 4 (6%) Decreased appetite, Grade 3 or 4 (2%) Abdominal pain, Grade 3 or 4 (2%) Musculoskeletal pain, Grade 3 or 4 (2%) Fatigue, Grade 3 or 4 (2%) Colitis (1.5%) Pneumonitis (1.2%) Constipation, Grade 3 or 4 (1%) Arthralgia, Grade 3 or 4 (1%) <1% Hepatitis Adrenal insufficiency Type 1 diabetes mellitus Nephritis

Anti-PD-L1 IgG1 monoclonal antibody PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells and can contribute to the inhibition of the antitumor immune response in the tumor microenvironment Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells and antigen-presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation, and cytokine production Avelumab binds PD-L1 and blocks interaction between PD-L1 and its receptors PD-1 and B7.1; therefore, inhibiting PD-L1, resulting in restoration of immune responses, including antitumor immune responses