An Investigational Immuno-therapy Study to Determine the Safety of Urelumab Given in Combination With Nivolumab in Solid Tumors and B-cell Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to determine which doses of Urelumab and Nivolumab are safe and tolerable when they are given together.

Official Title
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A Phase 1/2 Dose Escalation and Cohort Expansion Study of the Safety and Tolerability of Urelumab Administered in Combination With Nivolumab in Advanced/Metastatic Solid Tumors and B-cell Non-Hodgkins Lymphoma

Conditions
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Advanced Solid Tumors, Advanced B-cell NHL

Intervention / Treatment
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* Biological: Urelumab
* 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: For Dose Escalation: Subjects with any previously treated advanced (metastatic or refractory) solid tumor type and B-cell non-Hodgkin lymphoma For Cohort Expansion: Subjects must have a previously treated advanced solid tumor or B cell non-Hodgkin's lymphoma to be eligible Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 For certain subjects, willing and able to provide pre-treatment and on-treatment fresh tumor biopsy Women of child-bearing potential and men must use an acceptable method of contraception during treatment and for 23 weeks after treatment for women and 31 weeks for men Exclusion Criteria: Known 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 Uncontrolled or significant cardiovascular disease History of hepatitis (B or C) History of active or latent tuberculosis

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: Dose Escalation and Cohort expansion: Urelumab + Nivolumab<br>Nivolumab followed by Urelumab Nivolumab every 2 weeks up to 12 cycles and Urelumab every 4 weeks up to 6 cycles | Biological: Urelumab<br> <br> * Other names: BMS-663513;Biological: Nivolumab<br> <br> * Other names: BMS-936558;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Adverse Events. |  | From day 1 until 100 days after participant last dose of study drug. | 
| The Incidence of Seriuos Adverse Events. |  | From day 1 until 100 days after participant last dose of the study drug. | 
| The Incidence of Death. |  | From day 1 until 100 days after participant last dose of study drug. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) | The total number of subjects whose best overall response (BOR) is either a complete response or partial response for solid tumors and complete remission or partial remission for B-cell NHL, divided by the total number of subjects in the population of interest. | Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years. | 
| Objective Response Rate (ORR) | Objective response rate (ORR) is defined as the total number of subjects whose BOR is either CR or PR divided by the total number of subjects in the population of interest. | Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years. | 
| Occurrence of Specific Anti-drug Antibodies (ADA) to Urelumab and Nivolumab |  | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. | 
| Duration of Response (DOR) | DOR is defined as the number of days between the date of first response and the subsequent date of objectively documented disease progression based on the criteria (RECIST v1.1) or relapse based on IWG, or death due to any cause, if death occurred within 100 days after last dose, whichever occurs first. Data was not collected due to discontinuation of the study/Due to study termination. | Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years | 
| Progression-free Survival Rate (PFSR) | PFSR is defined as the probability of a subject remaining progression-free and surviving a specific length of time. Data was not collected due to discontinuation of the study/Due to study termination. | Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years. | 
| Maximum Observed Serum Concentration (Cmax) | Data was not collected due to discontinuation of the study/Due to study termination. | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. | 
| Time of Maximum Observed Serum Concentration (Tmax) | Data was not collected due to discontinuation of the study/Due to study termination. | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. | 
| Area Under the Concentration-time Curve in One Dosing Interval (AUCTAU) | Data was not collected due to discontinuation of the study/Due to study termination. | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days | 
| Trough Observed Plasma Concentration(Ctrough) | Data was not collected due to discontinuation of the study/Due to study termination. | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. | 
| End of Infusion Concentration (Ceoinf) | Data was not collected due to discontinuation of the study/Due to study termination. | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. | 
| Area Under the Plasma Concentration-time Curve, 0 to Time of Last Quantifiable Concentration (AUC(0-T) | Data was not collected due to discontinuation of the study/Due to study termination. | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. |