Active Ingredient: Enfortumab vedotin
Enfortumab vedotin, in combination with pembrolizumab, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial cancer who are eligible for platinum-containing chemotherapy.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Intravenous, between 1.25 milligrams enfortumab vedotin per kilogram of body weight and 125 milligrams enfortumab vedotin per kilogram of body weight, once every 7 days. The maximum allowed total dose is 125 milligrams enfortumab vedotin per kilogram of body weight every 7 days.
When given in combination with pembrolizumab, the recommended dose of enfortumab vedotin is 1.25 mg/kg (up to a maximum of 125 mg for patients ≥100 kg) administered as an intravenous infusion over 30 minutes on Days 1 and 8 of every 3-week (21-day) cycle until disease progression or unacceptable toxicity. The recommended dose of pembrolizumab is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes. Patients should be administered pembrolizumab after enfortumab vedotin when given on the same day. Refer to the pembrolizumab SmPC for additional dosing information of pembrolizumab.
Table 1. Recommended dose reductions for adverse reactions:
| Dose level | |
|---|---|
| Starting dose | 1.25 mg/kg up to 125 mg |
| First dose reduction | 1.0 mg/kg up to 100 mg |
| Second dose reduction | 0.75 mg/kg up to 75 mg |
| Third dose reduction | 0.5 mg/kg up to 50 mg |
Table 2. Dose interruption, reduction and discontinuation of enfortumab vedotin in patients with locally advanced or metastatic urothelial cancer:
| Adverse reaction | Severity* | Dose modification* |
|---|---|---|
| Skin reactions | Suspected Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) or bullous lesions | Immediately withhold and refer to specialised care |
| Confirmed SJS or TEN; Grade 4 or recurrent Grade 3 | Permanently discontinue. | |
| Grade 2 worsening Grade 2 with fever Grade 3 | • Withhold until Grade ≤1 • Referral to specialised care should be considered • Resume at the same dose level or consider dose reduction by one dose level (see Table 1) | |
| Hyperglycaemia | Blood glucose >13.9 mmol/L (>250 mg/dL) | • Withhold until elevated blood glucose has improved to ≤13.9 mmol/L (≤250 mg/dL) • Resume treatment at the same dose level |
| Pneumonitis/ interstitial lung disease (ILD) | Grade 2 | • Withhold until Grade ≤1, then resume at the same dose or consider dose reduction by one dose level (see Table 1). |
| Grade ≥3 | Permanently discontinue. | |
| Peripheral neuropathy | Grade 2 | • Withhold until Grade ≤1 • For first occurrence, resume treatment at the same dose level • For a recurrence, withhold until Grade ≤1 then, resume treatment reduced by one dose level (see Table 1) |
| Grade ≥3 | Permanently discontinue. |
* Toxicity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0) where Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe and Grade 4 is life-threatening.
The recommended dose must be administered by intravenous infusion over 30 minutes. Enfortumab vedotin must not be administered as an intravenous push or bolus injection.
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