Study of Urelumab in Subjects With Advanced and/or Metastatic Malignant Tumors

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of BMS-663513 in subjects with advanced and/or metastatic malignant tumors.

Official Title
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A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics and Immunoregulatory Activity of Urelumab (BMS-663513) in Subjects With Advanced and/or Metastatic Malignant Tumors

Conditions
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Malignant Tumors

Intervention / Treatment
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* Drug: Urelumab
* Drug: 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: Subjects with previously treated advanced malignant solid tumor Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 For certain subjects, willing and able to provide pre-treatment tumor sample Exclusion Criteria: Known or suspected central nervous system metastases or central nervous system as the only source of disease Other concomitant malignancies (with some exceptions per protocol) Active, known or suspected autoimmune disease

Ages Eligible for Study
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Minimum Age: 20 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: Urelumab (+ Nivolumab) intravenous (IV) infusion<br> | Drug: Urelumab<br> <br> Drug: Nivolumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of urelumab monotherapy as measured by the dose limiting toxicity (DLT) in subjects with advanced and/or metastatic malignant tumors |  | From day 1 of treatment up to 60 days of follow-up | 
| Safety of urelumab monotherapy as measured by adverse events (AEs) and serious adverse events (SAEs) in subjects with advanced and/or metastatic malignant tumors |  | From day 1 of treatment up to 60 days of follow-up | 
| Tolerability of urelumab monotherapy as measured by the DLT in subjects with advanced and/or metastatic malignant tumors |  | From day 1 of treatment up to 60 days of follow-up | 
| Tolerability of urelumab monotherapy as measured by AEs and SAEs in subjects with advanced and/or metastatic malignant tumors |  | From day 1 of treatment up to 60 days of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of urelumab-nivolumab combination therapy as measured by AEs and SAEs in subjects with advanced and/or metastatic malignant tumors |  | From day 1 of treatment up to 100 days of follow-up | 
| Tolerability of urelumab-nivolumab combination therapy as measured by AEs and SAEs in subjects with advanced and/or metastatic malignant tumors |  | From day 1 of treatment up to 100 days of follow-up | 
| Cmax (Maximum observed serum concentration) of urelumab when administered alone | 21 days/cycle for Urelumab monotherapy | Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up | 
| Ctrough (Trough observed serum concentration) of urelumab when administered alone | 21 days/cycle for Urelumab monotherapy | Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up | 
| Tmax (Time of maximum observed serum concentration) of urelumab when administered alone | 21 days/cycle for Urelumab monotherapy | Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up | 
| AUC(0-T) [Area under the concentration-time curve from time zero to the last quantifiable concentration] of urelumab when administered alone | 21 days/cycle for Urelumab monotherapy | Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up | 
| AUC(TAU) [Area under the concentration-time curve in one dosing interval] of urelumab when administered alone | 21 days/cycle for Urelumab monotherapy | Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up | 
| AUC(INF) [Area under the concentration-time curve from time zero to infinity and the extrapolated area] of urelumab when administered alone | 21 days/cycle for Urelumab monotherapy | Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up | 
| T-HALF (Elimination half life) of urelumab when administered alone | 21 days/cycle for Urelumab monotherapy | Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up | 
| CLT (Total body clearance) of urelumab when administered alone | 21 days/cycle for Urelumab monotherapy | Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up | 
| Vss (Volume of distribution at steady state) of urelumab when administered alone | 21 days/cycle for Urelumab monotherapy | Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up | 
| AI (Accumulation Index: ratio of AUC(TAU) and Cmax in cycle at steady state to those after the first cycle) of urelumab when administered alone | 21 days/cycle for Urelumab monotherapy | Cycle 1, 2, 3, 4, 5, 6, 7, 12, 16, up to 60 days of follow up | 
| Cmax of urelumab when co-administered | 28 days/cycle for combination therapy of Urelumab and Nivolumab | Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up | 
| Coeff of urelumab when co-administered | 28 days/cycle for combination therapy of Urelumab and Nivolumab | Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up | 
| Ctrough of urelumab and nivolumab when co-administered | 28 days/cycle for combination therapy of Urelumab and Nivolumab | Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up | 
| Tmax of urelumab and nivolumab when co-administered | 28 days/cycle for combination therapy of Urelumab and Nivolumab | Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up | 
| AUC(0-T) of urelumab and nivolumab when co-administered | 28 days/cycle for combination therapy of Urelumab and Nivolumab | Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up | 
| AUC(TAU) of urelumab and nivolumab when co-administered | 28 days/cycle for combination therapy of Urelumab and Nivolumab | Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up | 
| AUC(INF) of urelumab and nivolumab when co-administered | 28 days/cycle for combination therapy of Urelumab and Nivolumab | Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up | 
| T-HALF of urelumab when co-administered | 28 days/cycle for combination therapy of Urelumab and Nivolumab | Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up | 
| CLT of urelumab when co-administered | 28 days/cycle for combination therapy of Urelumab and Nivolumab | Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up | 
| Vss of urelumab when co-administered | 28 days/cycle for combination therapy of Urelumab and Nivolumab | Cycle 1, 2, 3, 4, 5, 6, 9, up to 100 days of follow up | 
| Anti-drug Antibody (ADA) status of the subject in response to Urelumab when administered alone | 21 days/cycle for Urelumab monotherapy | Cycle 1, 2, 4, 8, 12, 16, up to 60 days of follow up | 
| ADA status of the subject in response to Urelumab and Nivolumab when co-administered | 28 days/cycle for combination therapy of Urelumab and Nivolumab | Cycle 1, 2, 4, 5, 9, up to 100 days of follow up | 
| Best overall response (BOR) of urelumab monotherapy |  | Every 6-8 weeks during the treatment period | 
| BOR of urelumab and nivolumab combination therapy |  | Every 6-8 weeks during the treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced malignant tumors, Metastatic malignant tumors