A Phase I Open Label Study of the Safety and Tolerability of Elotuzumab (BMS-901608) Administered in Combination With Either Lirilumab (BMS-986015) or Urelumab (BMS-663513) in Subjects With Multiple Myeloma

Study Overview
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Brief Summary
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To assess the safety and tolerability, characterize the dose limiting toxicities (DLTs) and identify the maximally tolerated dose (MTD) of Elotuzumab administered in combination with either Lirilumab or Urelumab in subjects with multiple myeloma.

Detailed Description
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Allocation: Part1: Non-randomized Part2: Randomized

Official Title
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A Phase I Open Label Dose Escalation and Randomized Cohort Expansion Study of the Safety and Tolerability of Elotuzumab (BMS-901608) Administered in Combination With Either Lirilumab (BMS-986015) or Urelumab (BMS-663513) in Subjects With Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Elotuzumab
* Drug: Lirilumab
* Drug: Urelumab


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 must have histological confirmation of multiple myeloma with measurable disease (per International Myeloma Working Group (IMWG) criteria): Relapsed/refractory multiple myeloma, subjects who are post autologous transplant and have achieved very good partial response (VGPR) or complete response (nCR) with minimal residual disease (MRD)

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: Arm 1: Elotuzumab + Lirilumab<br>Elotuzumab weekly for 8 wks and every 2 wks thereafter + Lirilumab every 4 wks Intravenous solution for Up to 2 yrs, depending on response | Drug: Elotuzumab<br> <br> * Other names: BMS-901608;Drug: Lirilumab<br> <br> * Other names: BMS-986015;|
| Experimental: Arm 2: Elotuzumab + Urelumab<br>Elotuzumab weekly for 8 wks and every 2 wks thereafter + Urelumab every 4 wks Intravenous solution for Up to 26 weeks, depending on response | Drug: Elotuzumab<br> <br> * Other names: BMS-901608;Drug: Urelumab<br> <br> * Other names: BMS-663513;|

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 AEs, SAEs, deaths is the primary endpoint of this Phase 1 study. All subjects who receive at least one (full or partial) dose of Elotuzumab, Lirilumab or Urelumab will be evaluated for safety | adverse events (AEs), serious adverse events (SAEs) | During treatment and first 100 days after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) |  | At different timepoints approximately up to 2.5 years | 
| Objective Response rate (ORR) |  | At different timepoints approximately up to 2.5 years | 
| Median Duration of Response (mDOR) |  | At different timepoints approximately up to 2.5 years | 
| Median Time to Response (mTTR) |  | At different timepoints approximately up to 2.5 years | 
| Progression-free survival rate (PFSR) |  | At different timepoints approximately up to 2.5 years | 
| M-protein levels |  | At different timepoints approximately up to 2.5 years | 
| Minimal Residual Disease (MRD) status for Post Autologous Transplant subjects |  | At different timepoints approximately up to 2.5 years | 
| Maximum concentration of Urelumab (Cmax) |  | At different timepoints approximately up to 2.5 years | 
| Maximum concentration of Lirilumab (Cmax) |  | At different timepoints approximately up to 2.5 years | 
| Area under the Curve (AUCTAU) of Urelumab |  | At different timepoints approximately up to 2.5 years | 
| Area under the Curve (AUCTAU) of Lirilumab |  | At different timepoints approximately up to 2.5 years | 
| Volume of distribution (Vz) for Urelumab |  | At different timepoints approximately up to 2.5 years | 
| Total Clearance (CLT) of Urelumab |  | At different timepoints approximately up to 2.5 years | 
| Total Clearance (CLT) of Lirilumab |  | At different timepoints approximately up to 2.5 years | 
| Concentration at the end of infusion (ceoinf) of Urelumab |  | At different timepoints approximately up to 2.5 years | 
| Concentration at the end of infusion (ceoinf) of Elotuzumab |  | At different timepoints approximately up to 2.5 years | 
| Concentration at the end of infusion (ceoinf) of Lirilumab |  | At different timepoints approximately up to 2.5 years | 
| Cmin will be capture at steady state of all study subjects |  | At different timepoints approximately up to 2.5 years | 
| Occurence of Specific anti-drug antibodies (ADA) to each study drug |  | At different timepoints approximately up to 2.5 years | 
| ADA status of the subject Biomarkers: NK and T cell numbers, Phenotypic and functional measures in cohort expansion subjects |  | At different timepoints approximately up to 2.5 years |