Safety Study of IL-21/Anti-PD-1 Combination in the Treatment of Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the combination of the 2 drugs being investigated (IL-21 and anti-PD-1) is safe, and provide preliminary information on the clinical benefits of two different schedules of the combination.

Official Title
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A Phase 1 Dose Escalation Study of BMS-982470 (Recombinant Interleukin-21, rIL-21) in Combination With BMS-936558 (Anti-PD-1) in Subjects With Advanced or Metastatic Solid Tumors

Conditions
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Neoplasms by Site

Intervention / Treatment
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* Biological: Denenicokin
* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: All subjects will have locally advanced or metastatic solid tumors For Part 2 (Cohort Expansion): Tumor types will be restricted to clear cell renal cell carcinoma (ccRCC), non-small cell lung cancer (NSCLC), and melanoma At least 1 lesion with measurable disease Only subjects with tumor samples that are PD-L1 positive or negative are eligible Exclusion Criteria: Uncontrolled central nervous system (CNS) or leptomeningeal metastasis Inadequate liver or kidney function History of autoimmune Disease

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1-Arm A: BMS-982470 (weekly x 4) + BMS-936558<br>Dose Escalation BMS-982470 10, 30, 50, 75 or 100 µg/kg Solution, Intravenous, During each 6 week cycle: weekly x 4 (i.e during weeks 1 through 4), Up to 2 years + BMS-936558 3 mg/kg Solution, Intravenous, During each 6 week cycle: every other week (i.e during weeks 1, 3, and 5), Up to 2 years | Biological: Denenicokin<br> <br> * Other names: rIL-21(recombinant interleukin 21);Biological: Nivolumab<br> <br> * Other names: MDX-1106;|
| Experimental: Part 1-Arm B: BMS-982470 (3 times/week) + BMS-936558<br>Dose Escalation BMS-982470 10, 30, 50, 75 or 100 µg/kg Solution, Intravenous, During each 6 week cycle: 3 times/week during weeks 1 and 3, Up to 2 years + BMS-936558 3 mg/kg Solution, Intravenous, During each 6 week cycle: every other week (i.e during weeks 1, 3, and 5), Up to 2 years | Biological: Denenicokin<br> <br> * Other names: rIL-21(recombinant interleukin 21);Biological: Nivolumab<br> <br> * Other names: MDX-1106;|
| Experimental: Part 2-Arm A: BMS-982470 (weekly x 4) + BMS-936558<br>Cohort Expansion BMS-982470 (dose selected in Part 1) Solution, Intravenous, During each 6 week cycle: weekly x 4 (i.e during weeks 1 through 4), Up to 2 years + BMS-936558 3 mg/kg Solution, Intravenous, During each 6 week cycle: every other week (i.e during weeks 1, 3, and 5), Up to 2 years | Biological: Denenicokin<br> <br> * Other names: rIL-21(recombinant interleukin 21);Biological: Nivolumab<br> <br> * Other names: MDX-1106;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, as measured by the rate of adverse events and serious adverse events |  | Approximately up to 4.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as measured by tumor assessment (RECIST) | Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using Best overall response (BOR), Objective response rate (ORR), Duration of Response (DOR), Progression-Free Survival Rate (PFSR) | Week 6 of for the first 4 cycles, Week 6 of alternate cycle starting with cycle 6, End of Treatment (2 years) and approximately every 12 weeks during follow-up (approximately 1 year) | 
| Immunogenicity as measured by incidence of specific antidrug antibodies (ADA) to BMS-98470 and BMS-936558 |  | Up to 2 years + 100 days post-treatment follow-up |