Padcev Generic Name & Formulations
Mechanism of Action
As a single agent to treat locally advanced or metastatic urothelial cancer in adults who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or are ineligible for cisplatin-containing chemotherapy and have previously received ≥1 prior lines of therapy. In combination with pembrolizumab to treat locally advanced or metastatic urothelial cancer in adults who are not eligible for cisplatin-containing chemotherapy.
Padcev Dosage and Administration
Give by IV infusion over 30min. As a single agent: 1.25mg/kg (max 125mg for patients ≥100kg) on Days 1, 8 and 15 of a 28-day cycle; continue until disease progression or unacceptable toxicity. In combination with pembrolizumab: 1.25mg/kg (max 125mg for patients ≥100kg) on Days 1 and 8 of a 21-day cycle; continue until disease progression or unacceptable toxicity. Dose modifications: see full labeling.
Padcev Boxed Warnings
Severe cutaneous reactions (including SJS, TEN); monitor closely. Consider withholding for persistent or recurrent Grade 2 skin reactions until Grade ≤1. Withhold, consult a specialist to confirm for suspected SJS, TEN or for Grade 3 reactions; permanently discontinue if confirmed SJS or TEN, Grade 4 or recurrent Grade 3 reactions occur. Monitor blood glucose levels in patients with, or at risk of, diabetes or hyperglycemia; withhold dose if blood glucose >250mg/dL. Monitor for pneumonitis/ILD; withhold if Grade 2 reaction occurs and consider dose reduction; permanently discontinue if Grade 3 or 4 reaction. Monitor for new or worsening symptoms of peripheral neuropathy; consider dose interruption/reduction if occurs; permanently discontinue if Grade ≥3 reaction. Monitor for ocular disorders; if symptoms occur, consider ophthalmologic exam; interrupt/reduce dose if needed. Monitor for infusion site extravasation. Moderate or severe hepatic impairment (total bilirubin >1.5×ULN and any AST): avoid. Embryo-fetal toxicity. Advise to use effective contraception during and for 2 months (females) and for 4 months (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for ≥3 weeks after the last dose).
Peak ADC concentrations were observed near the end of intravenous infusion while peak unconjugated MMAE concentrations were observed approximately 2 days after enfortumab vedotin-ejfv dosing.
Steady-state concentrations of ADC and unconjugated MMAE were reached after 1 treatment cycle.
Exposure parameters of ADC and unconjugated MMAE after first treatment cycle of 1.25 mg/kg of enfortumab vedotin-ejfv dose of Days 1, 8 and 15:
- Mean Cmax (± SD): 28 (6.1) μg/mL (for ADC); 5.5 (3.0) ng/mL (for unconjugated MMAE)
- Mean AUC0-28d: 110 (26) μg∙d/mL (for ADC); 85 (50) ng∙d/mL (for unconjugated MMAE)
- Mean Ctrough,0-28d: 0.31 (0.18) μg/mL (for ADC); 0.81 (0.88) ng/mL (for unconjugated MMAE)
Estimated mean steady-state volume of distribution (for ADC): 12.8 L.
Plasma protein bound (for unconjugated MMAE): 68–82%, in vitro.
Half-life: 3.6 days (for ADC); 2.6 days (for unconjugated MMAE).
Mean clearance: 0.11 L/h (for enfortumab vedotin-ejfv); 2.11 L/h (for unconjugated MMAE).
Fecal (17%), renal (6%).
Padcev Adverse Reactions
Fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, dysgeusia, diarrhea, dry eye, pruritus, decreased weight, dry skin, anemia, lab abnormalities (increased AST/ALT, increased glucose, increased creatinine, decreased lymphocytes, decreased hemoglobin, decreased neutrophils, decreased platelets, decreased phosphate, decreased albumin, decreased sodium, increased urate, increased lipase). In combination with pembrolizumab: also constipation, peripheral edema, dry eye, dizziness, arthralgia, urinary tract infection, lab abnormalities (decreased/increased potassium, increased calcium).
Padcev Clinical Trials
Padcev Patient Counseling