Nivolumab Dose Optimization in Patients With a Complete, Partial or Stable Response
Status:
Recruiting
Trial end date:
2025-01-01
Target enrollment:
Participant gender:
Summary
Patients with advanced melanoma are, amongst others, currently treated with nivolumab
monotherapy or with nivolumab and ipilimumab followed by nivolumab. Even though registration
studies administered nivolumab in a 3 mg/kg 2 weekly scheme, currently, nivolumab monotherapy
is either administered in a 240 mg 2-weekly scheme or in a 6 mg/kg or 480 mg 4-weekly scheme.
With the current dosing regimen, steady-state is achieved after approximately 5 to 6 months,
whereas a tumour response is usually observed earlier in patients with metastatic melanoma.
Moreover, PD-1 receptor occupancy is almost saturated above doses of 0.3 mg/kg, or at
nivolumab serum levels of 10 mg/L, which is a concentration that is achieved after one
treatment cycle. In melanoma patients, the additional probability on response in patients
treated with 3 mg/kg compared to 1 mg/kg seems limited. PFS and OS for 3 mg/kg were not
superior to 1 mg/kg. Therefore, in this study, our aim is to investigate nivolumab trough
levels and pharmacokinetic parameters after 3 reduced nivolumab doses.