Comparing Dosing Intervals of Nivolumab or Pembrolizumab in Locally Advanced or Metastatic Cancers

Study Overview
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Brief Summary
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A randomized research study of drugs nivolumab and pembrolizumab in patients with locally advanced or metastatic cancers. Based on data from earlier studies it appears that the drugs can be given less often then the currently approved schedule. This trial will compare drug levels from the blood from standard interval dosing levels versus taking the drugs less often.

Official Title
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A Randomized Study Investigating the Pharmacokinetics of Standard Interval Dosing Compared to Extended Interval Dosing of Nivolumab or Pembrolizumab in Locally Advanced or Metastatic Cancers

Conditions
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Metastatic Cancer

Intervention / Treatment
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* Drug: Nivolumab Standard
* Drug: Pembrolizumab Standard
* Drug: Nivolumab Extended
* Drug: Pembrolizumab Extended


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with locally advandced or metastatic cancer whose physician has determined they are candidates for treatment with nivolumab or pembrolizumab 18 years old or older Measurable disease per RECIST criteria Exclusion Criteria: Patients who have previously received immune checkpoint inhibitors or investigational monoclonal antibody therapy. Patients whose treatment plan is to receive ipilimumab or other anti-CTLA4 monoclonal antibody in combination with either nivolumab or pembrolizumab. Ipilimumab and nivolumab combination are not eligible for this trial. (Note: Patients whose planned treatment is the combination of anti-PD-1 and tyrosine kinase inhibitor such as pembrolizumab-axitinib or the combination of traditional cytotoxic chemotherapy and anti-PD-1 are eligible)

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: standard interval dosing<br> | Drug: Nivolumab Standard<br>* For patients on standard schedule dosing of nivolumab, therapy will consist of 240mg IV once every 2 weeks or 480mg IV once every 4 weeks<br>Drug: Pembrolizumab Standard<br>* For patients on standard schedule dosing of pembrolizumab, therapy will consist of 200mg IV once every 3 weeks or 400mg IV once every 6 weeks<br>|
| Experimental: extended interval dosing<br> | Drug: Nivolumab Extended<br>* For patients on extended interval dosing of nivolumab therapy will consist of 240mg IV once every 4 weeks or 480mg IV once every 8 weeks<br>Drug: Pembrolizumab Extended<br>* For patients on extended interval dosing of pembrolizumab therapy will consist of 200mg IV once every 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Noninferiority margin of extended interval dosing compared to standard dosing | To assess the noninferiority of pharmacokinetic success, defined as drug trough levels above the target concentration of 1.5 µg/mL. Evaluable patients will be categorized as success or failure for this primary objective. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the efficacy of extended interval and standard interval dosing | To compare the correlation of extended interval and standard interval dosing, as based on a combination of time-to-treatment discontinuation (TTD) and overall survival (OS). This secondary analysis will include all patients who received at least one dose | 2 years |