Enfortumab Vedotin

Treatment should be initiated and supervised by a physician experienced in the use of anti-cancer therapies. Ensure good venous access prior to starting treatment. Neoadjuvant and adjuvant muscle-invasive bladder cancer (MIBC), in combination with pembrolizumab: 1.25 mg/kg (max 125 mg) IV over 30 minutes on Days 1 and 8 of each 3-week (21-day) cycle — neoadjuvant for 3 cycles or until disease progression that precludes radical cystectomy or unacceptable toxicity, then adjuvant for 6 cycles or until disease recurrence or unacceptable toxicity. Pembrolizumab dose is either 200 mg every 3 weeks or 400 mg every 6 weeks as an IV infusion over 30 minutes; pembrolizumab should be given after enfortumab vedotin when administered on the same day (refer to the pembrolizumab SmPC). Dose reduction schedule for adverse reactions: starting dose 1.25 mg/kg up to 125 mg; first reduction 1.0 mg/kg up to 100 mg; second reduction 0.75 mg/kg up to 75 mg; third reduction 0.5 mg/kg up to 50 mg. Withhold for Grade 2 worsening, Grade 2 with fever or Grade 3 skin reactions until Grade <= 1 then resume at the same or one reduced dose level; immediately withhold and refer to specialised care for suspected SJS/TEN or bullous lesions; permanently discontinue for confirmed SJS or TEN, Grade 4 or recurrent Grade 3 skin reactions. Withhold for blood glucose > 13.9 mmol/L (> 250 mg/dL) until improved to <= 13.9 mmol/L, then resume at the same dose level. Withhold for Grade 2 pneumonitis/ILD until Grade <= 1 then resume at the same dose or consider one dose-level reduction; permanently discontinue for Grade >= 3. Peripheral neuropathy Grade 2: withhold until Grade <= 1, resume at the same dose level for a first occurrence or reduced by one dose level for a recurrence; permanently discontinue for Grade >= 3. Elderly: no dose adjustment in patients >= 65 years. Hepatic impairment: no dose adjustment in mild impairment; only a limited number of patients with moderate or severe impairment have been evaluated and no specific dose recommendation can be given — monitor closely as exposure to MMAE is expected to increase. Paediatric: there is no relevant use of enfortumab vedotin in the paediatric population for locally advanced or metastatic urothelial cancer or MIBC. See SPC §6.6 for reconstitution and dilution.