Padcev

First-line (with pembrolizumab): In combination with pembrolizumab for adult patients with locally advanced or metastatic urothelial cancer, regardless of cisplatin eligibility.
Monotherapy: Adult patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy.

Combination with pembrolizumab: 1.25 mg/kg (max 125 mg) IV on Days 1 and 8 of a 21-day cycle, with pembrolizumab 200 mg IV on Day 1
Monotherapy: 1.25 mg/kg (max 125 mg) IV over 30 minutes on Days 1, 8, and 15 of a 28-day cycle
Dose reductions: First: 1.0 mg/kg; Second: 0.75 mg/kg; Third: 0.5 mg/kg

For injection: 20 mg, 30 mg lyophilized powder in single-dose vial

None listed in the prescribing information.

• Skin Reactions: Severe cutaneous adverse reactions including SJS and TEN reported (fatal cases). Monitor for skin reactions and withhold/permanently discontinue as indicated.
• Hyperglycemia: New onset or worsening hyperglycemia including DKA and hyperosmolarity reported (fatal cases). Monitor blood glucose.
• Pneumonitis: ILD/pneumonitis reported. Monitor and permanently discontinue for Grade 2 or higher.
• Peripheral Neuropathy: Monitor for new or worsening symptoms. Withhold or discontinue based on severity.
• Ocular Disorders: Dry eye, blurred vision, increased lacrimation, and other disorders reported.
• Embryo-Fetal Toxicity: Can cause fetal harm.

Rash (55%), Fatigue (50%), Peripheral Neuropathy (49%), Alopecia (42%), Decreased Appetite (42%), Dysgeusia (37%), Nausea (36%), Diarrhea (34%), Dry Eye (30%), Pruritus (26%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions. No formal drug interaction studies have been conducted.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Enfortumab vedotin is an antibody-drug conjugate consisting of a fully human anti-Nectin-4 IgG1κ monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a protease-cleavable maleimidocaproyl valine-citrulline linker. Nectin-4 is a cell adhesion molecule expressed in urothelial cancers. Upon binding to Nectin-4, the ADC undergoes internalization, linker cleavage, and MMAE release, disrupting the microtubule network and inducing cell cycle arrest and apoptosis.

Tmax: end of infusion. ADC Half-life: ~3.4 days. MMAE Half-life: ~2.6 days. Vd (ADC): 11.4 L. Protein binding (MMAE): 68–82%. MMAE metabolized by CYP3A4. Elimination: MMAE primarily in feces. Steady state by Cycle 1.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• EV-302/KEYNOTE-A39 — Enfortumab vedotin + pembrolizumab vs. chemotherapy in first-line advanced urothelial cancer. Phase III, n=886.
  🔬 NCT04223856 ↗ 📄 Primary Publication ↗
• EV-301 — Enfortumab vedotin vs. chemotherapy in previously treated advanced urothelial cancer. Phase III, n=608.
  🔬 NCT03474107 ↗ 📄 Primary Publication ↗

Padcev has FDA-approved indications across the following cancer types covered on CancerDrugEvidence: