An Investigational Immuno-therapy Study of Nivolumab, Pomalidomide and Dexamethasone Combinations in Patients With Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of several combination therapies for Multiple Myeloma. Upon entry into the study, patients will be randomized (assigned by chance) to receive either: Group 1: nivolumab, pomalidomide and dexamethasone OR Group 2: pomalidomide and dexamethasone OR Group 3: nivolumab, elotuzumab, pomalidomide and dexamethasone. Enrollment is closed for all groups.

Official Title
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An Open-Label, Randomized Phase 3 Trial of Combinations of Nivolumab, Pomalidomide and Dexamethasone in Relapsed and Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: Nivolumab
* Biological: Elotuzumab
* Drug: Pomalidomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refractory or relapsed and refractory multiple myeloma Measurable disease Have received ≥ 2 lines of prior therapy which must have included an immune modulatory drug (IMiD) and a proteasome inhibitor alone or in combination Exclusion Criteria: Solitary bone or extramedullary plasmacytoma disease only Active plasma cell leukemia Other protocol defined inclusion/exclusion criteria apply

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: Investigational Arm<br>Nivolumab, Pomalidomide and Dexamethasone Enrollment is closed for this arm | Biological: Nivolumab<br>* Specified dose on specified days, IV (intravenous)<br>* Other names: BMS-936558;Drug: Pomalidomide<br>* Specified dose on specified days, PO (by mouth)<br>Drug: Dexamethasone<br>* Specified dose on specified days, PO<br>|
| Active Comparator: Control Arm<br>Pomalidomide and Dexamethasone Enrollment is closed for this arm | Drug: Pomalidomide<br>* Specified dose on specified days, PO (by mouth)<br>Drug: Dexamethasone<br>* Specified dose on specified days, PO<br>|
| Experimental: Exploratory Arm<br>Nivolumab, Elotuzumab, Pomalidomide and Dexamethasone Enrollment is closed for this arm | Biological: Nivolumab<br>* Specified dose on specified days, IV (intravenous)<br>* Other names: BMS-936558;Biological: Elotuzumab<br>* Specified dose on specified days, IV<br>* Other names: BMS-901608;Drug: Pomalidomide<br>* Specified dose on specified days, PO (by mouth)<br>Drug: Dexamethasone<br>* Specified dose on specified days, PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Randomization to first documented tumor progression or death due to any cause, whichever occurred first. Participants who die without reported prior progression are considered to have progressed on date of their death. Participants who did not progress or die will be censored at their last efficacy assessment. Participants who did not have on study efficacy assessments and alive will be censored on randomization date. Participants who started subsequent anti-cancer therapy without prior reported progression will be censored at last efficacy assessment prior to subsequent anti-cancer therapy. Progression is 1) increase of 25% from lowest confirmed response value in specific Serum M-protein and Urine M-protein criteria and increase of FLC for patients with no measurable M protein in blood or urine at baseline and/or 2) appearance of a new lesion(s), >/= 50% increase from nadir in SPD of > 1 lesion, or >/= 50% increase in the longest diameter of a previous lesion > 1 cm in short axis. | From randomization to the date of the first documented tumor progression or death due to any cause, whichever occurred first (Up to approximately 64 month) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | The time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a participant was known to be alive. | From randomization to the date of death due to any cause (up to approximately 64 months) | 
| Objective Response Rate (ORR) | The percentage of randomized participants who achieved a best overall response (BOR) of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) using International Myeloma Working Group (IMWG) criteria. sCR= Complete response as defined below plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry. CR = Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates. VGPR = Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >/= 90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 h. PR = >/= 50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by >/= 90% or to < 200 mg per 24 h. | From randomization up to approximately 64 months | 
| Time to Objective Response (TTR) | The time from the date of randomization to the date of the first stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). sCR= Complete response as defined below plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry. CR = Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow aspirates. VGPR = Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >/= 90% reduction in serum M-protein plus urine M-protein level < 100 mg per 24 h. PR = >/= 50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by >/= 90% or to < 200 mg per 24 h. | From the date of randomization to the date of the first sCR, CR, VGPR, or PR (up to approximately 64 months) | 
| Duration of Objective Response (DOR) | The time between the date of first response to the date of the first objectively documented tumor progression as assessed by the investigator according to International Myeloma Working Group (IMWG) criteria or death due to any cause prior to subsequent anti-cancer therapy. Participants who neither progress nor die will be censored on the date of their last tumor assessment prior to subsequent anti-cancer therapy. Progression is 1) increase of 25% from lowest confirmed response value in specific Serum M-protein and Urine M-protein criteria and increase of FLC for patients with no measurable M protein in blood or urine at baseline and/or 2) appearance of a new lesion(s), >/= 50% increase from nadir in SPD of > 1 lesion, or >/= 50% increase in the longest diameter of a previous lesion > 1 cm in short axis. | From randomization to the date of the first objectively documented tumor progression or death due to any cause prior to subsequent anti-cancer therapy (up to approximately 64 months) |