NIVOPTIMIZE: Nivolumab Dose Optimization in Patients With a Complete, Partial or Stable Response
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Nivolumab Patients in the experimental arm receive three reduced nivolumab doses of 240 mg Q4W |
Drug: Nivolumab
Participants receive three reduced doses of 240 mg every four weeks
|
Outcome Measures
Primary Outcome Measures
- 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]
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.
Secondary Outcome Measures
- - PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses [Through study completion, an average of four months]
- PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses
- Grade ≥3 adverse events (CTCAE) during reduced doses [Through study completion, an average of four months]
Grade ≥3 adverse events (CTCAE) during reduced doses
- Number of patients with new PD during 3 reduced doses [Through study completion, an average of four months]
Number of patients with new PD during 3 reduced doses
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Erasmus MC | Rotterdam | Pending | Netherlands |
Sponsors and Collaborators
- Erasmus Medical Center
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NL77343.078.21