Japanese Study of BMS-901608 (Elotuzumab) in Combination With Lenalidomide and Low Dose Dexamethasone

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01241292
• Collaborator: (none)
• Enrollment: 7
• Locations: 3
• Arms: 2
• Actual Duration (Months): 72.1
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and tolerability of Elotuzumab when given in combination with Lenalidomide and low-dose Dexamethasone in subjects with relapsed or refractory multiple myeloma (MM) in Japan.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Biological: BMS-901608 (Elotuzumab) 10 mg; Biological: BMS-901608 (Elotuzumab) 20 mg	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1 Multiple Ascending Dose Study of Elotuzumab (BMS-901608) in Combination With Lenalidomide/Low-dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma in Japan
• Actual Study Start Date: Jan 14, 2011
• Actual Primary Completion Date: Feb 14, 2014
• Actual Study Completion Date: Jan 16, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BMS-901608 (Elotuzumab) 10mg	Biological: BMS-901608 (Elotuzumab) 10 mg; Injection, Intravenous, 10 mg/kg, Weekly at cycle 1 and 2, bi-weekly at cycle 3 and thereafter, Until disease progression or unacceptable toxicity became apparent
Experimental: BMS-901608 (Elotuzumab) 20mg	Biological: BMS-901608 (Elotuzumab) 20 mg; Injection, Intravenous, 20 mg/kg, Weekly at cycle 1 and 2, bi-weekly at cycle 3 and thereafter, Until disease progression or unacceptable toxicity became apparent

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths [First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)]

   AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Data cut-off February 2014.

2. Number of Participants With Clinically Relevant Vital Sign Findings [First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)]

   Vital signs (body temperature, seated blood pressure, heart rate, and respiration rate) were recorded at screening on Days 1, 8, 15, and 22 of Cycles 1 and 2, on Days 1 and 15 of Cycle 3, and at the end of treatment. Blood pressure (Diastolic and Systolic) and heart rate were recorded after the participant sat quietly for at least 5 minutes. Clinical relevance of vital sign data was determined by the investigator.

3. Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests [First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)]

   National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Lymphocytes (absolute) Gr 1: <1.5 to 0.8 *10^3 c/µL, Gr 2 <0.8 to 0.5 *10^3 c/µL, Gr 3: <0.5 to 0.2 *10^3 c/µL, Gr 4: <0.2*10^3 c/µL. Neutrophils (absolute): Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Leukocytes Gr 1:<LLN to 3.0 *10^3 c/µL, Gr 2; <3.0 to 2.0 *10^3 c/µL, Gr 3: <2.0 to 1.0 *10^3 c/µL, Gr 4: <1.0 *10^3 c/µL.

4. Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests [First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)]

   National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:>1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. AST Gr 1: >1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 1: >1.0 to 1.5*ULN; Gr 2: >1.5 to 3.0*ULN; Gr 3: >3.0 to 10..0*ULN; Gr 4: >10.0.0*ULN. ALP (U/L) Gr1:>1.0 to 2.5*ULN, Gr2:>2.5 to 5.0*ULN, Gr3:>5.0 to 20.0*ULN, Gr4:>20.0*ULN. Albumin (low) Gr 1:<LLN to 3 grams per deciliter (g/dL); Gr 2: <3.0 - 2.0 g/L; Gr 3: < 2 g/dL. Creatinine Gr 1: >1 - 1.5*baseline (BL)to >ULN - 1.5*ULN; Gr 2: >1.5 - 3.0*BL to > 1.5 - 3.0*ULN; Gr 3: >3.0*BL to > 3.0 - 6.0*ULN; Gr 4: >6.0*ULN.

5. Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests [First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)]

   NCI CTCAE, version 3.0 was used to measure toxicity scale. Sodium high (H) Gr 1:>ULN - 150; Gr 2: >150 - 155; Gr 3: >155 - 160; Gr 4: >160 mmol/L; Sodium low(L) Gr 1:<LLN - 130; Gr 3: <130 - 120; Gr 4: <120 mmol/L. Potassium (H) Gr 1: >ULN - 5.5; Gr 2: >5.5 - 6.0; Gr 3: > 6.0 - 7.0; Gr 4: >7.0 mmol/L; Potassium (L) Gr 1 - Gr 2: <LLN - 3.0; Gr 3: < 3.0 - 2.5; Gr 4: <2.5 mmol/L.

Secondary Outcome Measures

1. Number of Participants With Best Overall Response - Treated Participants [Cycle 2 (Study Day 29) to last dose (assessed up to January 2017, approximately 71 months)]

   Complete response (CR) and Partial Response (PR) were based on the European Group for Blood and Bone Marrow Transplant (EBMT) Criteria. Very Good Partial response was derived from the International Myeloma Working Group (IMWG) criteria. Participants who had a reduction in M-protein or plasmacytoma but did not meet the EBMT criteria for PR were classified as minimal response (MR). Hematologic, radiologic and/or clinical assessments were done every cycle starting with cycle 2. Each cycle is 4 weeks in length (Day 1, Day 8, Day 15, Day 22). Cycle 2 began on study Day 29. CR=negative immunofixation 6 weeks, <5% plasma cells, no increase in size or number of lytic lesions, complete disappearance of extramedullary plasmacytoma. PR=≥50%reduction in M-protein for 6 weeks, ≥90% reduction of urinary light chain excretion or < 200 mg/24hours for 6 weeks, ≥50% reduction in size of extramedullary plasmacytoma present at baseline, no increase in size or number of lytic lesions.

2. Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3 [Days 1, 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3]

   The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmax was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h.

3. Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3 [Days 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3]

   The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmin was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h.

4. Number of Participants Positive for Anti-Elotuzumab Anti-drug Antibodies - Treated Participants [First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)]

   The detection of anti-elotuzumab anti-drug antibodies (ADAs) in human serum was performed using a validated bridging electrochemiluminescence immunoassay (ECLA) on the Meso Scale Discovery (MSD) platform. Sample collection was performed prior to administration of elotuzumab at Day 1 of each cycle.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For additional information, please contact the BMS oncology clinical trial information service at 855-216-0126 or email [e-mail]. Please visit www.BMSStudyConnect.com for more information on clinical trial participation.

Inclusion Criteria:

• Received between 1 to 4 prior lines of therapy

• Measureable disease

• Men and women of childbearing potential (WOCBP) must be using two acceptable methods of contraception

• Men must agree to use a latex condom and a second form of birth control during sexual contact with WOCBP and must agree to not donate semen during study drug therapy

• Subjects must be willing to refrain from blood donations during study drug therapy

Exclusion Criteria:

• Subjects with non-secretory or oligo-secretory or light-chain only myeloma or active/prior plasma cell leukemia or known /suspect POEMS syndrome

• Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia

• Unable to take aspirin daily as prophylactic anticoagulation therapy. Prior history of inability to tolerate weekly 40 mg dexamethasone

• History of renal failure

• History of clinical significant thrombosis, such as treatment for thrombosis was required

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Nagoya-shi	Aichi	Japan	4600001
2	Local Institution	Nagoya-shi	Aichi	Japan	4678602
3	Local Institution	Niigata-shi	Niigata	Japan	9518566

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS Clinical Trial Patient Recruiting

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01241292
• Other Study ID Numbers: CA204-005
• First Posted: Nov 16, 2010
• Last Update Posted: Feb 15, 2018
• Last Verified: Jan 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Elotuzumab

Study Results

Participant Flow

Pre-assignment Detail	Seven participants were enrolled and 6 entered the treatment period. Reason for 1 participant not entering treatment period: participant no longer met study criteria.

Arm/Group Title	Elotuzumab 10 mg/kg	Elotuzumab 20 mg/kg
Arm/Group Description	Elotuzumab 10 mg/kg was intravenously (IV) given weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity. Elotuzumab was first given at 10 mg/kg. If all participants completed the first cycle and none experienced a dose limiting toxicity (DLT), the dose was escalated to 20 mg/kg. If 1 experienced a DLT at 10 mg/kg, 3 additional participants were assigned to 10 mg/kg. If no additional participants experienced a DLT, the dose was escalated to 20 mg/kg. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. On weeks without elotuzumab, dexamethasone was administered as a single oral (PO) dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (3 to 24 hours prior to the start of elotuzumab) and 8 mg IV (45 min prior to start of elotuzumab).	Elotuzumab 20 mg/kg was intravenously (IV) given weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity. Elotuzumab was first given at 10 mg/kg. If all participants completed the first cycle and none experienced a dose limiting toxicity (DLT), the dose was escalated to 20 mg/kg. If 1 experienced a DLT at 10 mg/kg, 3 additional participants were assigned to 10 mg/kg. If no additional participants experienced a DLT, the dose was escalated to 20 mg/kg. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. On weeks without elotuzumab, dexamethasone was administered as a single oral (PO) dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (3 to 24 hours prior to the start of elotuzumab) and 8 mg IV (45 min prior to start of elotuzumab).
Period Title: Overall Study
STARTED	3	3
Entered Treatment Period	3	3
COMPLETED	0	0
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Elotuzumab 10 mg/kg	Elotuzumab 20 mg/kg	Total
Arm/Group Description	Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Total of all reporting groups
Overall Participants	3	3	6
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61.0	66.0	63.5
Age, Customized (participants) [Number]
Less than (<) 65	2 66.7%	1 33.3%	3 50%
65 to < 75	1 33.3%	1 33.3%	2 33.3%
Greater than, equal to 75	0 0%	1 33.3%	1 16.7%
Sex: Female, Male (Count of Participants)
Female	1 33.3%	2 66.7%	3 50%
Male	2 66.7%	1 33.3%	3 50%
Region of Enrollment (participants) [Number]
Japan	3 100%	3 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation, Deaths
Description	AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. Data cut-off February 2014.
Time Frame	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study medication were summarized (Treated Participants).

Arm/Group Title	Elotuzumab 10 mg/kg	Elotuzumab 20 mg/kg
Arm/Group Description	Elotuzumab was intravenously (IV) injected at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab was intravenously (IV) injected at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered as a single dose of 40 mg PO. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) AND 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Measure Participants	3	3
All SAEs Any Grade	2 66.7%	3 100%
Grade 3-4 SAEs	1 33.3%	3 100%
AEs Leading to Discontinuation	0 0%	1 33.3%
Grade 3-4 AEs	3 100%	3 100%
Deaths	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Clinically Relevant Vital Sign Findings
Description	Vital signs (body temperature, seated blood pressure, heart rate, and respiration rate) were recorded at screening on Days 1, 8, 15, and 22 of Cycles 1 and 2, on Days 1 and 15 of Cycle 3, and at the end of treatment. Blood pressure (Diastolic and Systolic) and heart rate were recorded after the participant sat quietly for at least 5 minutes. Clinical relevance of vital sign data was determined by the investigator.
Time Frame	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study medication were summarized.

Arm/Group Title	Elotuzumab 10 mg/kg	Elotuzumab 20 mg/kg
Arm/Group Description	Elotuzumab was administered IV at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab was administered IV at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Measure Participants	3	3
Number [participants]	0 0%	0 0%

3. Secondary Outcome

Title	Number of Participants With Best Overall Response - Treated Participants
Description	Complete response (CR) and Partial Response (PR) were based on the European Group for Blood and Bone Marrow Transplant (EBMT) Criteria. Very Good Partial response was derived from the International Myeloma Working Group (IMWG) criteria. Participants who had a reduction in M-protein or plasmacytoma but did not meet the EBMT criteria for PR were classified as minimal response (MR). Hematologic, radiologic and/or clinical assessments were done every cycle starting with cycle 2. Each cycle is 4 weeks in length (Day 1, Day 8, Day 15, Day 22). Cycle 2 began on study Day 29. CR=negative immunofixation 6 weeks, <5% plasma cells, no increase in size or number of lytic lesions, complete disappearance of extramedullary plasmacytoma. PR=≥50%reduction in M-protein for 6 weeks, ≥90% reduction of urinary light chain excretion or < 200 mg/24hours for 6 weeks, ≥50% reduction in size of extramedullary plasmacytoma present at baseline, no increase in size or number of lytic lesions.
Time Frame	Cycle 2 (Study Day 29) to last dose (assessed up to January 2017, approximately 71 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study medication were summarized (Treated Participants).

Arm/Group Title	Elotuzumab 10 mg/kg	Elotuzumab 20 mg/kg
Arm/Group Description	Elotuzumab was administered IV at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab was administered IV at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Measure Participants	3	3
Complete Response	0 0%	1 33.3%
Very Good Partial Response	1 33.3%	2 66.7%
Partial Response	1 33.3%	0 0%
Minimal Response	1 33.3%	0 0%

4. Secondary Outcome

Title	Geometric Mean Maximum Observed Serum Elotuzumab Concentration (Cmax) During Cycles 1, 2, and 3
Description	The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmax was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h.
Time Frame	Days 1, 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study medication and had adequate Pharmacokinetic (PK) concentration profiles were summarized.

Arm/Group Title	Elotuzumab 10 mg/kg	Elotuzumab 20 mg/kg
Arm/Group Description	Elotuzumab was administered IV at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab was administered IV at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Measure Participants	3	3
Cycle 1 Day 1 (n=3,3)	173 (9)	376 (14)
Cycle 1 Day 8 (n=3,3)	237 (19)	549 (18)
Cycle 1 Day 15 (n=3,3)	297 (10)	652 (21)
Cycle 1 Day 22 (n=3,2)	234 (14)	724 (45)
Cycle 2 Day 1 (n=3,3)	240 (28)	671 (51)
Cycle 2 Day 22 (n=3,3)	270 (32)	844 (26)
Cycle 3 Day 1 (n=3,3)	286 (32)	972 (32)

5. Secondary Outcome

Title	Geometric Mean Minimum Observed Serum Elotuzumab Concentration (Cmin) During Cycles 1, 2, and 3
Description	The quantification of elotuzumab in human serum was performed using a validated enzyme-linked immunosorbent assay (ELISA). Cmin was measured in micrograms per milliliter (µg/mL). Samples of serum were obtained at: Cycle 1, Day 1: 0 hour (h), 30 minutes (min) 2 h post dose; Day 8: 0h, 2 h; Day 15: 0h, 30 min; Day 22: 0h, 30min, 2h. Cycle 2, Day 1, 22 0h, 2h. Cycle 3, Day 1: 0h, 30h, 2h; Day 15: 0h.
Time Frame	Days 8, 15 and 22 of cycle 1, Days 1 and 22 of cycle 2, Days 1 and 15 of cycle 3

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study medication and had adequate PK concentration profiles were summarized.

Arm/Group Title	Elotuzumab 10 mg/kg	Elotuzumab 20 mg/kg
Arm/Group Description	Elotuzumab was administered IV at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab was administered IV at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Measure Participants	3	3
Cycle 1 Day 8 (n=3,3)	59.1 (28)	165 (20)
Cycle 1 Day 15 (n=3,3)	97.0 (12)	252 (30)
Cycle 1 Day 22 (n=3,2)	24.6 (87)	280 (62)
Cycle 2 Day 1 (n=3,2)	25.8 (95)	389 (64)
Cycle 2 Day 22 (n=3,3)	57.8 (82)	547 (41)
Cycle 3 Day 1 (n=3,3)	77.2 (78)	579 (46)
Cycle 3 Day 15 (n=3,3)	59.4 (78)	466 (38)

6. Primary Outcome

Title	Number of Participants With Worst Toxicity Grade Hematology Laboratory Tests
Description	National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Lymphocytes (absolute) Gr 1: <1.5 to 0.8 *10^3 c/µL, Gr 2 <0.8 to 0.5 *10^3 c/µL, Gr 3: <0.5 to 0.2 *10^3 c/µL, Gr 4: <0.2*10^3 c/µL. Neutrophils (absolute): Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Leukocytes Gr 1:<LLN to 3.0 *10^3 c/µL, Gr 2; <3.0 to 2.0 *10^3 c/µL, Gr 3: <2.0 to 1.0 *10^3 c/µL, Gr 4: <1.0 *10^3 c/µL.
Time Frame	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study medication were summarized.

Arm/Group Title	Elotuzumab 10 mg/kg	Elotuzumab 20 mg/kg
Arm/Group Description	Elotuzumab was administered IV at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab was administered IV at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Measure Participants	3	3
Hemoglobin Any Grade	3 100%	3 100%
Hemoglobin Grade 3-4	0 0%	1 33.3%
Lymphocytes Any Grade	3 100%	3 100%
Lymphocytes Grade 3-4	3 100%	3 100%
Neutrophils Any Grade	3 100%	3 100%
Neutrophils Grade 3-4	2 66.7%	3 100%
Platelet Count Any Grade	3 100%	2 66.7%
Platelet Count Grade 3-4	1 33.3%	0 0%
Leukocytes Any Grade	3 100%	3 100%
Leukocytes Grade 3-4	2 66.7%	1 33.3%

7. Primary Outcome

Title	Number of Participants With Worst Toxicity Grade Renal and Liver Function Laboratory Tests
Description	National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 was used to measure toxicity scale. Lower Limits of Normal (LLN). Upper Limits of Normal (ULN). Alanine transaminase (ALT); Aspartate aminotransferase (AST); Alkaline phosphatase (ALP). ALT Grade (Gr)1:>1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. AST Gr 1: >1.0 to 2.5*ULN; Gr 2: >2.5 to 5.0*ULN; Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 1: >1.0 to 1.5*ULN; Gr 2: >1.5 to 3.0*ULN; Gr 3: >3.0 to 10..0*ULN; Gr 4: >10.0.0*ULN. ALP (U/L) Gr1:>1.0 to 2.5*ULN, Gr2:>2.5 to 5.0*ULN, Gr3:>5.0 to 20.0*ULN, Gr4:>20.0*ULN. Albumin (low) Gr 1:<LLN to 3 grams per deciliter (g/dL); Gr 2: <3.0 - 2.0 g/L; Gr 3: < 2 g/dL. Creatinine Gr 1: >1 - 1.5*baseline (BL)to >ULN - 1.5*ULN; Gr 2: >1.5 - 3.0*BL to > 1.5 - 3.0*ULN; Gr 3: >3.0*BL to > 3.0 - 6.0*ULN; Gr 4: >6.0*ULN.
Time Frame	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study medication were summarized.

Arm/Group Title	Elotuzumab 10 mg/kg	Elotuzumab 20 mg/kg
Arm/Group Description	Elotuzumab was administered IV at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab was administered IV at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Measure Participants	3	3
Albumin Any Grade	3 100%	3 100%
Albumin Grade 3-4	0 0%	0 0%
ALP Any Grade	1 33.3%	2 66.7%
ALP Grade 3-4	0 0%	0 0%
ALT Any Grade	2 66.7%	2 66.7%
ALT Grade 3-4	1 33.3%	1 33.3%
AST Any Grade	1 33.3%	2 66.7%
AST Grade 3-4	1 33.3%	1 33.3%
Creatinine Any Grade	0 0%	2 66.7%
Creatinine Grade 3-4	0 0%	0 0%
Bilirubin Total Any Grade	1 33.3%	0 0%
Bilirubin Total Grade 3-4	0 0%	0 0%

8. Primary Outcome

Title	Number of Participants With Worst Toxicity Grade Chemistry Laboratory Tests
Description	NCI CTCAE, version 3.0 was used to measure toxicity scale. Sodium high (H) Gr 1:>ULN - 150; Gr 2: >150 - 155; Gr 3: >155 - 160; Gr 4: >160 mmol/L; Sodium low(L) Gr 1:<LLN - 130; Gr 3: <130 - 120; Gr 4: <120 mmol/L. Potassium (H) Gr 1: >ULN - 5.5; Gr 2: >5.5 - 6.0; Gr 3: > 6.0 - 7.0; Gr 4: >7.0 mmol/L; Potassium (L) Gr 1 - Gr 2: <LLN - 3.0; Gr 3: < 3.0 - 2.5; Gr 4: <2.5 mmol/L.
Time Frame	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study medication were summarized.

Arm/Group Title	Elotuzumab 10 mg/kg	Elotuzumab 20 mg/kg
Arm/Group Description	Elotuzumab 10 mg/kg was intravenously (IV) given weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity. Elotuzumab was first given at 10 mg/kg. If all participants completed the first cycle and none experienced a dose limiting toxicity (DLT), the dose was escalated to 20 mg/kg. If 1 experienced a DLT at 10 mg/kg, 3 additional participants were assigned to 10 mg/kg. If no additional participants experienced a DLT, the dose was escalated to 20 mg/kg. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. On weeks without elotuzumab, dexamethasone was administered as a single oral (PO) dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (3 to 24 hours prior to the start of elotuzumab) and 8 mg IV (45 min prior to start of elotuzumab).	Elotuzumab 20 mg/kg was intravenously (IV) given weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity. Elotuzumab was first given at 10 mg/kg. If all participants completed the first cycle and none experienced a dose limiting toxicity (DLT), the dose was escalated to 20 mg/kg. If 1 experienced a DLT at 10 mg/kg, 3 additional participants were assigned to 10 mg/kg. If no additional participants experienced a DLT, the dose was escalated to 20 mg/kg. Lenalidomide 25 mg was administered orally once daily for the first 3 weeks of each 4-week cycle. On weeks without elotuzumab, dexamethasone was administered as a single oral (PO) dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (3 to 24 hours prior to the start of elotuzumab) and 8 mg IV (45 min prior to start of elotuzumab).
Measure Participants	3	3
Potassium High, Any Grade	0 0%	2 66.7%
Potassium High, Grade 3-4	0 0%	0 0%
Potassium Low, Any Grade	3 100%	2 66.7%
Potassium Low, Grade 3-4	0 0%	1 33.3%
Sodium High, Any Grade	1 33.3%	2 66.7%
Sodium High, Grade 3-4	0 0%	0 0%
Sodium Low, Any Grade	2 66.7%	3 100%
Sodium Low, Grade 3-4	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants Positive for Anti-Elotuzumab Anti-drug Antibodies - Treated Participants
Description	The detection of anti-elotuzumab anti-drug antibodies (ADAs) in human serum was performed using a validated bridging electrochemiluminescence immunoassay (ECLA) on the Meso Scale Discovery (MSD) platform. Sample collection was performed prior to administration of elotuzumab at Day 1 of each cycle.
Time Frame	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study medication were summarized.

Arm/Group Title	Elotuzumab 10 mg/kg	Elotuzumab 20 mg/kg
Arm/Group Description	Elotuzumab was administered IV at a dose of 10 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).	Elotuzumab was administered IV at a dose of 20 mg/kg weekly (Days 1, 8, 15 and 22 of 4-week cycle) for the first 2 cycles and bi-weekly (every 2 weeks) (Day 1 and Day 15) thereafter until disease progression or unacceptable toxicity became apparent. Lenalidomide 25 mg was administered PO once daily for the first 3 weeks of each 4-week cycle. The dose of lenalidomide was administered at least 2-4 hours after completion of elotuzumab infusion. On weeks without elotuzumab administration, dexamethasone was administered PO as a single dose of 40 mg. On weeks of elotuzumab infusion, the weekly dose of dexamethasone was administered as a split dose of: 28 mg PO (between 3 to 24 hours prior to the start of the elotuzumab infusion) and 8 mg IV (At least 45 min prior to the start of the elotuzumab infusion).
Measure Participants	3	3
Number [participants]	3 100%	0 0%

Adverse Events

Time Frame	First dose (Day 1) to last dose plus 60 days (assessed up to January 2017, approximately 71 months)
Arm/Group Title	BMS 10mg/kg + Ld		BMS 20mg/kg + Ld
Arm/Group Description
All Cause Mortality
	BMS 10mg/kg + Ld		BMS 20mg/kg + Ld
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)
Serious Adverse Events
	BMS 10mg/kg + Ld		BMS 20mg/kg + Ld
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		3/3 (100%)
Eye disorders
Cataract	1/3 (33.3%)		1/3 (33.3%)
Hepatobiliary disorders
Cholelithiasis	0/3 (0%)		1/3 (33.3%)
Hepatitis	1/3 (33.3%)		0/3 (0%)
Infections and infestations
Pneumonia	0/3 (0%)		1/3 (33.3%)
Investigations
Alanine aminotransferase increased	0/3 (0%)		1/3 (33.3%)
Aspartate aminotransferase increased	0/3 (0%)		1/3 (33.3%)
Blood alkaline phosphatase increased	0/3 (0%)		1/3 (33.3%)
Gamma-glutamyltransferase increased	0/3 (0%)		1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	0/3 (0%)		1/3 (33.3%)
Other (Not Including Serious) Adverse Events
	BMS 10mg/kg + Ld		BMS 20mg/kg + Ld
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Anaemia	1/3 (33.3%)		0/3 (0%)
Granulocytopenia	0/3 (0%)		1/3 (33.3%)
Leukopenia	3/3 (100%)		3/3 (100%)
Lymphopenia	3/3 (100%)		3/3 (100%)
Neutropenia	3/3 (100%)		2/3 (66.7%)
Thrombocytopenia	2/3 (66.7%)		0/3 (0%)
Cardiac disorders
Atrioventricular block first degree	0/3 (0%)		1/3 (33.3%)
Eye disorders
Cataract	1/3 (33.3%)		1/3 (33.3%)
Conjunctival haemorrhage	0/3 (0%)		1/3 (33.3%)
Eye discharge	0/3 (0%)		1/3 (33.3%)
Gastrointestinal disorders
Constipation	2/3 (66.7%)		2/3 (66.7%)
Dental caries	0/3 (0%)		2/3 (66.7%)
Diarrhoea	2/3 (66.7%)		2/3 (66.7%)
Epigastric discomfort	1/3 (33.3%)		0/3 (0%)
Eructation	0/3 (0%)		1/3 (33.3%)
Gingival erosion	0/3 (0%)		1/3 (33.3%)
Nausea	2/3 (66.7%)		0/3 (0%)
Proctalgia	0/3 (0%)		1/3 (33.3%)
Stomatitis	1/3 (33.3%)		1/3 (33.3%)
Vomiting	1/3 (33.3%)		1/3 (33.3%)
General disorders
Chest pain	0/3 (0%)		1/3 (33.3%)
Fatigue	1/3 (33.3%)		1/3 (33.3%)
Malaise	0/3 (0%)		2/3 (66.7%)
Oedema	1/3 (33.3%)		0/3 (0%)
Pyrexia	3/3 (100%)		1/3 (33.3%)
Immune system disorders
Seasonal allergy	1/3 (33.3%)		0/3 (0%)
Infections and infestations
Cystitis	0/3 (0%)		1/3 (33.3%)
Herpes simplex	1/3 (33.3%)		0/3 (0%)
Herpes zoster	0/3 (0%)		1/3 (33.3%)
Infection	0/3 (0%)		1/3 (33.3%)
Influenza	1/3 (33.3%)		0/3 (0%)
Nasopharyngitis	2/3 (66.7%)		2/3 (66.7%)
Oral fungal infection	0/3 (0%)		1/3 (33.3%)
Periodontitis	0/3 (0%)		1/3 (33.3%)
Pneumonia	0/3 (0%)		1/3 (33.3%)
Injury, poisoning and procedural complications
Arthropod sting	1/3 (33.3%)		0/3 (0%)
Contusion	1/3 (33.3%)		0/3 (0%)
Laceration	1/3 (33.3%)		0/3 (0%)
Skin abrasion	0/3 (0%)		1/3 (33.3%)
Wound	0/3 (0%)		1/3 (33.3%)
Investigations
Alanine aminotransferase increased	1/3 (33.3%)		1/3 (33.3%)
Amylase increased	0/3 (0%)		1/3 (33.3%)
Aspartate aminotransferase increased	1/3 (33.3%)		1/3 (33.3%)
Blood alkaline phosphatase increased	1/3 (33.3%)		0/3 (0%)
Blood creatine phosphokinase increased	1/3 (33.3%)		0/3 (0%)
Creatinine renal clearance decreased	1/3 (33.3%)		1/3 (33.3%)
Electrocardiogram qt prolonged	1/3 (33.3%)		0/3 (0%)
Haemoglobin decreased	0/3 (0%)		1/3 (33.3%)
Weight decreased	0/3 (0%)		1/3 (33.3%)
Metabolism and nutrition disorders
Glucose tolerance impaired	1/3 (33.3%)		0/3 (0%)
Hypertriglyceridaemia	1/3 (33.3%)		1/3 (33.3%)
Hypoalbuminaemia	0/3 (0%)		1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Back pain	1/3 (33.3%)		0/3 (0%)
Musculoskeletal pain	0/3 (0%)		1/3 (33.3%)
Myalgia	1/3 (33.3%)		1/3 (33.3%)
Nervous system disorders
Dizziness	1/3 (33.3%)		0/3 (0%)
Dysgeusia	2/3 (66.7%)		3/3 (100%)
Headache	1/3 (33.3%)		1/3 (33.3%)
Neuropathy peripheral	0/3 (0%)		1/3 (33.3%)
Somnolence	0/3 (0%)		1/3 (33.3%)
Psychiatric disorders
Insomnia	2/3 (66.7%)		1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/3 (0%)		1/3 (33.3%)
Hiccups	1/3 (33.3%)		0/3 (0%)
Skin and subcutaneous tissue disorders
Dry skin	0/3 (0%)		2/3 (66.7%)
Haemorrhage subcutaneous	1/3 (33.3%)		0/3 (0%)
Haemorrhage subepidermal	1/3 (33.3%)		0/3 (0%)
Penile ulceration	1/3 (33.3%)		0/3 (0%)
Rash	2/3 (66.7%)		2/3 (66.7%)
Vascular disorders
Flushing	0/3 (0%)		2/3 (66.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.