Tivdak(tisotumab vedotin)

Tivdak (tisotumab vedotin) is indicated as monotherapy for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy. The recommended dose is 2 mg/kg every 3 weeks, with a maximum dose of 200 mg for patients ≥ 100 kg. The marketing authorization application was submitted on 12 January 2024, and a positive opinion was issued on 30 January 2025.

In clinical trials, Tivdak demonstrated a median overall survival of 11.7 months and an objective response rate (CR+PR) of 17.8%. For comparison, platinum-based chemotherapy plus bevacizumab showed a median OS of 17 months versus 13.3 months for chemotherapy alone, and Pembrolizumab plus platinum-based chemotherapy with/without bevacizumab (PDL-1 CPS≥1) achieved a median OS of 28.6 months versus 16.5 months for placebo/chemotherapy +/- bevacizumab. Cemiplimab showed an OS of 12.0 months versus 8.5 months for single-agent chemotherapy in previously untreated checkpoint inhibitor patients.

Safety findings indicate that MMAE exposure, a component of Tivdak, can increase by 34% with strong CYP3A4/5 inhibitors and 37% with mild hepatic impairment, and decrease by 46% with CYP3A4/5 inducers. Specifically, ketoconazole increased MMAE exposure by 134%, while rifampin decreased it by 54%. Treatment-related TEAEs leading to dose discontinuations had p-values of 0.031 and 0.028, and those leading to dose reductions and interruptions had a p-value of <0.0005. MMAE exposure was a predictor of treatment-related TEAEs leading to dose discontinuations (p-value 0.013).