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Does tolerability for Padcev® impact clinical adoption? PADCEVⓇ Prescribing Information HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use PADCEV safely and effectively. See full prescribing information for PADCEV. PADCEV (enfortumab vedotin-ejfv) for injection, for intravenous use Initial U.S. Approval: 2019 WARNING: SERIOUS SKIN REACTIONS See full prescribing information for complete boxed warning. PADCEV can cause severe and fatal cutaneous adverse reactions, including Stevens-Johnson syndrome (SIS) and Toxic Epidermal Necrolysis (TEN). Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions. (2.2), (5.1) (6.1) . RECENT MAJOR CHANGES Indications and Usage (1) Dosage and Administration (22) Warnings and Precautions (5.1). (5.2). (5.3). (5.4). (5.6) 4/2023 10/2022 4/2023 INDICATIONS AND USAGE PADCEV is a Nectin-4-directed antibody and microtubule inhibitor conjugate indicated: as a single agent for the treatment of adult patients with locally advanced or metastatic urothelial cancer who: 0 have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand I (PD-L1) inhibitor and platinum- containing chemotherapy, or O are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy. (1) in combination with pembrolizumab for the treatment of adult patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing chemotherapy. (1) This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. (14.1) DOSAGE AND ADMINISTRATION For intravenous infusion only. Do not administer PADCEV as an intravenous push or bolus. Do not mix with, or administer as an infusion with, other medicinal products. (23) The recommended dose of PADCEV as a single agent is 1.25 mg/kg (up to a maximum dose of 125 mg) given as an intravenous infusion over 30 minutes on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. (21) The recommended dose of PADCEV in combination with pembrolizumab is 1.25 mg kg (up to a maximum dose of 125 mg) given as an intravenous infusion over 30 minutes on Days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity. (2.1) Avoid use in patients with moderate or severe hepatic impairment (8.6) DOSAGE FORMS AND STRENGTHS For Injection: 20 mg and 30 mg of enfortumab vedotin-ejfv as a lyophilized powder in a single-dose vial for reconstitution. (3) None. (4) WARNINGS AND PRECAUTIONS . Hyperglycemia: Diabetic ketoacidosis may occur in patients with and without preexisting diabetes mellitus, which may be fatal. Closely /monitor blood glucose levels in patients with, or at risk for, diabetes. mellitus or hyperglycemia. Withhold PADCEV if blood glucose i e is >250 mg/dl. (22.5.2) . CONTRAINDICATIONS . Pneumonitis/Interstitial Lung Disease (ILD): Severe, life-threatening or fatal pneumonitis ILD may occur. Withhold PADCEV for Grade 2 pneumonitis/ILD and consider dose reduction Permanently discontinue PADCEV for Grade 3 or 4 pneumonitis/ILD. (2.2, 5.3) Peripheral Neuropathy: Monitor patients for new or worsening peripheral neuropathy and consider dose interruption, dose reduction of discontinuation of PADCEV. (2.2. 5.4) Infusion Site Extravasation: Ensure adequate venous access prior to administration. Monitor the infusion site during PADCEV administration and stop the infusion immediately for suspected extravasation. (5.6) . Embryo-Fetal Toxicity: PADCEV can cause fetal harm. Advise of the potential risk to a fetus and to use effective contraception. (5.7. 8.1, 8.3) ADVERSE REACTIONS The most common adverse reactions, including laboratory abnormalities, (220%) were: PADCEV as a single agent: rash, aspartate aminotransferase increased. glucose increased, creatinine increased, fatigue, peripheral neuropathy, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased and dry skin. (6.1) PADCEV in combination with pembrolizumab: glucose increased, aspartate aminotransferase increased, rash, hemoglobin decreased, creatinine increased, peripheral neuropathy, lymphocytes decreased, fatigue, alanine aminotransferase increased, sodium decreased, lipase increased, albumin decreased, alopecia, phosphate decreased, decreased weight, diarrhea, pruritus, decreased appetite, nausea, dysgeusia. potassium decreased, neutrophils decreased, urinary tract infection, constipation, potassium increased, calcium increased, peripheral edema, dry eye, dizziness, arthralgia, and dry skin. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch Ocular Disorders: Ocular disorders, including vision changes, may occur. Monitor patients for signs or symptoms of ocular disorders. Consider prophylactic artificial tears for dry eyes and treatment with ophthalmic topical steroids after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV when symptomatic ocular disorders occur. (5.5) DRUG INTERACTIONS Concomitant use of dual P-gp and strong CYP3A4 inhibitors with PADCEV may increase the exposure to monomethyl auristatin E (MMAE) (7.1) -USE IN SPECIFIC POPULATIONS . Lactation: Advise women not to breastfeed. (8.2) See 17 for PATIENT COUNSELING INFORMATION and FDA- approved patient labeling Source(s): PADCEVⓇ Prescribing Information as of Apr 2023. Revised: 4/2023 Revised: 4/2023 1 T 61% Dose interruptions PADCEVⓇ enfortumab vedotin-ejfv Injection for IV infusion 20 mg & 30 mg vials Duration of Response ~5 months 47% Rate of Serious Adverse Events (SAES) T 34% Dose reductions T 17% Dose Discontinuations EV-301: The safety of PADCEV was evaluated as a single agent in EV-301 in patients with locally advanced or metastatic urothelial cancer (n=296] who received at least one dose of PADCEV 1.25 mg/kg and who were previously treated with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy

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