Nivolumab Dose Optimization in Patients With a Complete, Partial or Stable Response

Study Overview
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Brief Summary
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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.

Official Title
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Nivolumab Dose Optimization in Patients With a Complete, Partial or Stable Response

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Advanced or metastatic melanoma Current treatment with nivolumab for advanced or metastatic melanoma, in a 6 mg/kg or 480 mg, 4 weekly scheme Documented confirmed and ongoing CR, PR or SD according to RECIST v1.1 On treatment for at least 6 months Exclusion Criteria: Unable to draw blood for study purposes Patients willing to participate or already included in the SAFE-STOP trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nivolumab<br>Patients in the experimental arm receive three reduced nivolumab doses of 240 mg Q4W | Drug: Nivolumab<br>* Participants receive three reduced doses of 240 mg every four weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference between the nivolumab mean trough level after 3 reduced doses (240 mg every 4 weeks) and after the first dose of 6 mg/kg or 480 mg. | Difference between the nivolumab mean trough level after 3 reduced doses (240 mg every 4 weeks) and after the first dose of 6 mg/kg or 480 mg. | Through study completion, an average of four months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| - PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses | - PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses | Through study completion, an average of four months | 
| Grade ≥3 adverse events (CTCAE) during reduced doses | Grade ≥3 adverse events (CTCAE) during reduced doses | Through study completion, an average of four months | 
| Number of patients with new PD during 3 reduced doses | Number of patients with new PD during 3 reduced doses | Through study completion, an average of four months |