Enfortumab vedotin
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| ID | DRUG-ENFORTUMAB-VEDOTIN |
|---|---|
| Tipo | Fármaco |
| Aliaces | ASG-22MEEl Sr.Enfortumab vedotin-ejfvЕнфортумаб ведотин |
| Situación | reviewed 2026-04-27 | pending_clinical_signoff |
| Enfermedades | DIS-UROTHELIAL |
| Fuentes | SRC-EAU-BLADDER-2024 SRC-NCCN-BLADDER-2025 |
Datos sobre drogas
| Clase | Conjugado anticuerpos-fármaco dirigidos a la nectina-4 (carga útil de las MMAE) |
|---|---|
| Mecanismo | Fully human anti-Nectin-4 IgG1κ monoclonal antibody (AGS-22M6) conjugated via a protease-cleavable maleimidocaproyl-valine- citrulline-PAB linker to monomethyl auristatin E (MMAE), a potent microtubule-disrupting cytotoxic payload (drug-to-antibody ratio ~3.8). Nectin-4 (PVRL4) is highly expressed in urothelial carcinoma (>95% of mUC cases), with limited normal-tissue expression (skin keratinocytes, salivary gland — accounting for characteristic skin and ocular AEs). After antigen binding the ADC is internalized; lysosomal cleavage releases MMAE, which binds tubulin and induces G2/M arrest and apoptosis. Pivotal EV-302 (1L locally advanced / metastatic urothelial carcinoma: enfortumab vedotin + pembrolizumab vs platinum-based chemo): mPFS 12.5 vs 6.3 mo HR 0.45, mOS 31.5 vs 16.1 mo HR 0.47 — first combination to surpass platinum chemo as 1L mUC standard, paradigm-shifting; FDA full appr... |
| Dosificación típica | 1.25 mg/kg (capped at 125 mg per dose for patients ≥100 kg) IV over 30 minutes on Days 1, 8, 15 of each 28-day cycle. With or without pembrolizumab 200 mg IV q3w (per EV-302; pembrolizumab given Day 1 of each pembro cycle). Continue until disease progression / unacceptable toxicity. Dose level -1 = 1.0 mg/kg; -2 = 0.75 mg/kg; -3 = 0.5 mg/kg; permanent discontinuation if recurrent G3-4 at -3. Hold for G3-4 skin toxicity, G3-4 hyperglycemia, G3-4 peripheral neuropathy, G3-4 ocular toxicity, pneumonitis, severe infusion reaction. Renal: no formal adjustment for CrCl ≥30; not studied in severe renal impairment. Hepatic: avoid in moderate-severe hepatic impairment (no PK data). |
| Ucrania registrada | Falso |
| NSZU reembolsado | Falso |
| Ucrania verificada por última vez | 2026-04-27 |
Advertencias
- Reacciones adversas cutáneas graves y fatales (en caja) - incluyendo SJS / TEN / DRESS / SCAR; pueden poner en peligro su vida; ordenar la suspensión inmediata de cualquier nueva reacción cutánea peor que la erupción cutánica maculopapular, consulta dermatológica y suspensión permanente de las reacciones SJs / NET / G4
Notas
EV-302 (NEJM 2024 Powles): paradigm-shifting trial that moved enfortumab+pembrolizumab to 1L mUC SoC, displacing platinum-based chemo. mOS doubling (31.5 vs 16.1 mo) is among the largest ever reported in mUC. Hyperglycemia is the signal AE — monitor fasting glucose weekly first 4 weeks then with each cycle, especially in diabetic / pre-diabetic / obese patients (BMI >30); proactive metformin and insulin adjustment. Mandatory baseline + ongoing ophthalmologic exam; lubricating drops continuously; corticosteroid drops for keratitis. Skin toxicity escalation algorithm: hold and dermatology consult for any new rash with pustules, target lesions, or mucosal involvement (SJS suspicion); permanent discontinuation for SJS/TEN. Counsel patients on neuropathy onset (gloves/socks early symptom). UA access via EAP / cross-border / self-pay only — not on НСЗУ. EV-302 access pathway is the dominant 1L mUC standard in EU centers via "Лікування за кордоном" (наказ МОЗ 988).
Utilizado por
Esquema terapéutico
REG-EV-MONO-UROTHELIAL- Enfortumab vedotin monotherapy (urothelial carcinoma)REG-EV-PEMBRO-UROTHELIAL- Enfortumab vedotin + pembrolizumab (metastatic urothelial, 1L)