Info

🌱 來自：Antibody Drug Conjugates

Enfortumab vedotin

kfsyscc-of-Enfortumab vedotin

• Mechanism:
  • Anti-Nectin 4 human IgG1;
  • after binding, internalized ADC releases antimicrotubule agent MMAE, producing cell cycle arrest/apoptosis
• Approved indication:
  • Urothelial cancer
• Dosing:
  • 1.25 mg/kg (max 125 mg) IV d 1, 8, & 15 of 28-d cycles;
  • avoid use in mod./sev. hepatic impairment;
  • no adjustment for renal impairment;
  • manufacturer-recommended dose reductions available for toxicity
• PK/PD:
  • T1/2 3.4 d for ADC, 2.4 d for MMAE;
  • MMAE metabolized hepatically (CYP3A4)
• Adverse effects (AEs):
  • Skin rxns (mostly maculopapular rash/pruritus, some sev. rxns),
  • hyperglycemia,
  • peripheral neuropathy,
  • ocular disorders (mostly corneal),
  • alopecia,
  • diarrhea,
  • dysgeusia,
  • low vomiting risk,
  • myelosuppression
• DDI: Strong CYP3A4 inhibitors/inducers likely increase/decrease MMAE exposure; no specific dose adjustments recommended; MMAE is a P-glycoprotein substrate

Clinical pearls

• Prophylactic artificial tears suggested;
• median 3.8 mos to grade ≥2 neuropathy, 1.9 mos to ocular disorders

Tirals

1. Powles T, Valderrama BP, Gupta S, et al. LBA6 EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). Annals of Oncology. 2023;34:S1340-S1340. doi:https://doi.org/10.1016/j.annonc.2023.10.106