Clincosm LogoSign in Get a demo

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

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Terminated
CT.gov ID
NCT02253992
Collaborator
(none)
232
Enrollment
17
Locations
1
Arm
55.8
Actual Duration (Months)
13.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Biological: Urelumab
  • Biological: Nivolumab
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
232 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Sep 29, 2014
Actual Primary Completion Date :
May 24, 2019
Actual Study Completion Date :
May 24, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation and Cohort expansion: Urelumab + Nivolumab

Nivolumab followed by Urelumab Nivolumab every 2 weeks up to 12 cycles and Urelumab every 4 weeks up to 6 cycles

Biological: Urelumab
Other Names:
  • BMS-663513

    • Biological: Nivolumab
    Other Names:
  • BMS-936558

    		•

    Outcome Measures

    Primary Outcome Measures

    1. The Incidence of Adverse Events. [From day 1 until 100 days after participant last dose of study drug.]

    2. The Incidence of Seriuos Adverse Events. [From day 1 until 100 days after participant last dose of the study drug.]

    3. The Incidence of Death. [From day 1 until 100 days after participant last dose of study drug.]

    Secondary Outcome Measures

    1. Best Overall Response (BOR) [Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years.]

      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.

    2. Objective Response Rate (ORR) [Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years.]

      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.

    3. Occurrence of Specific Anti-drug Antibodies (ADA) to Urelumab and Nivolumab [Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.]

    4. Duration of Response (DOR) [Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years]

      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.

    5. Progression-free Survival Rate (PFSR) [Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years.]

      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.

    6. Maximum Observed Serum Concentration (Cmax) [Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.]

      Data was not collected due to discontinuation of the study/Due to study termination.

    7. Time of Maximum Observed Serum Concentration (Tmax) [Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.]

      Data was not collected due to discontinuation of the study/Due to study termination.

    8. Area Under the Concentration-time Curve in One Dosing Interval (AUCTAU) [Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days]

      Data was not collected due to discontinuation of the study/Due to study termination.

    9. Trough Observed Plasma Concentration(Ctrough) [Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.]

      Data was not collected due to discontinuation of the study/Due to study termination.

    10. End of Infusion Concentration (Ceoinf) [Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.]

      Data was not collected due to discontinuation of the study/Due to study termination.

    11. Area Under the Plasma Concentration-time Curve, 0 to Time of Last Quantifiable Concentration (AUC(0-T) [Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.]

      Data was not collected due to discontinuation of the study/Due to study termination.

    Eligibility Criteria

    Criteria

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

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Stanford University School Of Medicine Palo Alto California United States 94304
    2 H. Lee Moffitt Cancer Center Tampa Florida United States 33612
    3 University Of Chicago Chicago Illinois United States 60637
    4 Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Lutherville Maryland United States 21093
    5 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    6 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    7 NYU Langone Medical Center New York New York United States 10016
    8 Memorial Sloan Kettering Nassau New York New York United States 10065
    9 Providence Portland Medical Center Portland Oregon United States 97213
    10 UPMC Cancer Center Pittsburgh Pennsylvania United States 15213
    11 Md Anderson Houston Texas United States 77030
    12 Local Institution Besancon France 25000
    13 Local Institution Marseille France 13005
    14 Local Institution Rennes Cedex 9 France 35033
    15 Local Institution Villejuif France 94805
    16 Universitaetsklinikum Essen Essen Germany 45147
    17 Clinica Universidad de Navarra Pamplona Spain 31008

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT02253992
    Other Study ID Numbers:
    • CA186-107
    • 2014-002241-22
    First Posted:
    Oct 1, 2014
    Last Update Posted:
    Oct 5, 2020
    Last Verified:
    Sep 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lymphoma, Non-Hodgkin
    Lymphoma, B-Cell
    Nivolumab

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 160 enrolled and treated
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Period Title: Overall Study
    STARTED 6 4 150
    COMPLETED 0 0 6
    NOT COMPLETED 6 4 144

    Baseline Characteristics

    Arm/Group Title TRT A TRT B TRT D Total
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK Total of all reporting groups
    Overall Participants 6 4 150 160
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    1
    16.7%
    2
    50%
    67
    44.7%
    70
    43.8%
    >=65 years
    5
    83.3%
    2
    50%
    83
    55.3%
    90
    56.3%
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    64.7
    (9.40)
    64.0
    (8.52)
    63.8
    (11.71)
    63.9
    (11.52)
    Sex: Female, Male (Count of Participants)
    Female
    2
    33.3%
    2
    50%
    47
    31.3%
    51
    31.9%
    Male
    4
    66.7%
    2
    50%
    103
    68.7%
    109
    68.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    1
    25%
    1
    0.7%
    2
    1.3%
    Not Hispanic or Latino
    5
    83.3%
    2
    50%
    107
    71.3%
    114
    71.3%
    Unknown or Not Reported
    1
    16.7%
    1
    25%
    42
    28%
    44
    27.5%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    1
    0.7%
    1
    0.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    9
    6%
    9
    5.6%
    White
    6
    100%
    4
    100%
    136
    90.7%
    146
    91.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    4
    2.7%
    4
    2.5%

    Outcome Measures

    1. Primary Outcome
    Title The Incidence of Adverse Events.
    Description
    Time Frame From day 1 until 100 days after participant last dose of study drug.

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Measure Participants 6 4 150
    Number [Number of participants]
    6
    100%
    4
    100%
    150
    100%
    2. Primary Outcome
    Title The Incidence of Seriuos Adverse Events.
    Description
    Time Frame From day 1 until 100 days after participant last dose of the study drug.

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Measure Participants 6 4 150
    Number [Number of participants]
    3
    50%
    3
    75%
    86
    57.3%
    3. Primary Outcome
    Title The Incidence of Death.
    Description
    Time Frame From day 1 until 100 days after participant last dose of study drug.

    Outcome Measure Data

    Analysis Population Description
    All Treated participants
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Measure Participants 6 4 150
    Number [Number of participants]
    6
    100%
    2
    50%
    93
    62%
    4. Secondary Outcome
    Title Best Overall Response (BOR)
    Description 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.
    Time Frame Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years.

    Outcome Measure Data

    Analysis Population Description
    All treated Participants
    Arm/Group Title TRT D - NSCLC pd1/Pd-l1 Experienced TRT D - NSCLC pd1/Pd-l1 Naive TRT D - Melanoma pd1/Pd-l1 Experienced TRT A - Melanoma pd1/Pd-l1 Naive TRT B - TRT D - Melanoma pd1/Pd-l1 Naive TRT A - SCCHN TRT D - SCCHN TRT A - Other Solid Tumors TRT B - Other Solid Tumors TRT D - DLBCL TRT D - FL
    Arm/Group Description URE8 Q4WK+NIV240mg Q2WK- Non small cell lung cancer pd1/pd-l1 experienced URE8 Q4WK+NIV240mg Q2WK - Non samll cell lung cancer pd1/pd-l1 naive. URE8 Q4WK+NIV240mg Q2WK - Melanoma pd1/pd-l1 experienced URE3 Q4WK+NIV3 Q2WK - Melanoma pd1/pd-l1 naive URE8 Q4WK+NIV3 Q2WK - Melanoma pd1/pd-l1 naive URE8 Q4WK+NIV240mg Q2WK - Melanoma pd1/pd-l1 naive URE3 Q4WK+NIV3 Q2WK - Squamous cell carcinoma of head and neck. URE8 Q4WK+NIV240mg Q2WK - Squamous cell carcinoma of head and neck. URE3 Q4WK+NIV3 Q2WK - Other solid tumors URE8 Q4WK+NIV3 Q2WK - Other Solid tumors. URE8 Q4WK+NIV240mg Q2WK - Diffuse Large B-cell lymphoma. URE8 Q4WK+NIV240mg Q2WK - Follicular Lymphoma.
    Measure Participants 20 20 20 4 1 43 1 21 1 3 22 4
    Complete response
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    NaN
    6
    NaN
    0
    NaN
    1
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    Partial response
    1
    16.7%
    1
    25%
    2
    1.3%
    1
    0.6%
    0
    NaN
    15
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    5. Secondary Outcome
    Title Objective Response Rate (ORR)
    Description 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.
    Time Frame Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years.

    Outcome Measure Data

    Analysis Population Description
    All treated Participants
    Arm/Group Title TRT D - NSCLC pd1/Pd-l1 Experienced TRT D - NSCLC pd1/Pd-l1 Naive TRT D - Melanoma pd1/Pd-l1 Experienced TRT A - Melanoma pd1/Pd-l1 Naive TRT B - TRT D - Melanoma pd1/Pd-l1 Naive TRT A - SCCHN TRT D - SCCHN TRT A - Other Solid Tumors TRT B - Other Solid Tumors TRT D - DLBCL TRT D - FL
    Arm/Group Description URE8 Q4WK+NIV240mg Q2WK- Non small cell lung cancer pd1/pd-l1 experienced URE8 Q4WK+NIV240mg Q2WK - Non samll cell lung cancer pd1/pd-l1 naive. URE8 Q4WK+NIV240mg Q2WK - Melanoma pd1/pd-l1 experienced URE3 Q4WK+NIV3 Q2WK - Melanoma pd1/pd-l1 naive URE8 Q4WK+NIV3 Q2WK - Melanoma pd1/pd-l1 naive URE8 Q4WK+NIV240mg Q2WK - Melanoma pd1/pd-l1 naive URE3 Q4WK+NIV3 Q2WK - Squamous cell carcinoma of head and neck. URE8 Q4WK+NIV240mg Q2WK - Squamous cell carcinoma of head and neck. URE3 Q4WK+NIV3 Q2WK - Other solid tumors URE8 Q4WK+NIV3 Q2WK - Other Solid tumors. URE8 Q4WK+NIV240mg Q2WK - Diffuse Large B-cell lymphoma. URE8 Q4WK+NIV240mg Q2WK - Follicular Lymphoma.
    Measure Participants 20 20 20 4 1 43 1 21 1 3 22 4
    Number (95% Confidence Interval) [Percentage of participants]
    5.0
    83.3%
    5.0
    125%
    10.0
    6.7%
    25.0
    15.6%
    100.0
    NaN
    48.8
    NaN
    0
    NaN
    4.8
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    0
    NaN
    6. Secondary Outcome
    Title Occurrence of Specific Anti-drug Antibodies (ADA) to Urelumab and Nivolumab
    Description
    Time Frame Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Urelumab ADA Nivolumab ADA
    Arm/Group Description Urelumab Anti drug antibody Nivolumab anti drug antibody
    Measure Participants 133 128
    Baseline ADA positive
    5
    83.3%
    2
    50%
    ADA positive
    55
    916.7%
    9
    225%
    ADA negative
    78
    1300%
    119
    2975%
    7. Secondary Outcome
    Title Duration of Response (DOR)
    Description 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.
    Time Frame Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years

    Outcome Measure Data

    Analysis Population Description
    Data was not collected due to discontinuation of the study/Due to study termination.
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Measure Participants 0 0 0
    8. Secondary Outcome
    Title Progression-free Survival Rate (PFSR)
    Description 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.
    Time Frame Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years.

    Outcome Measure Data

    Analysis Population Description
    Data was not collected due to discontinuation of the study/Due to study termination.
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Measure Participants 0 0 0
    9. Secondary Outcome
    Title Maximum Observed Serum Concentration (Cmax)
    Description Data was not collected due to discontinuation of the study/Due to study termination.
    Time Frame Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.

    Outcome Measure Data

    Analysis Population Description
    Data was not collected due to discontinuation of the study/Due to study termination.
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Measure Participants 0 0 0
    10. Secondary Outcome
    Title Time of Maximum Observed Serum Concentration (Tmax)
    Description Data was not collected due to discontinuation of the study/Due to study termination.
    Time Frame Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.

    Outcome Measure Data

    Analysis Population Description
    Data was not collected due to discontinuation of the study/Due to study termination.
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Measure Participants 0 0 0
    11. Secondary Outcome
    Title Area Under the Concentration-time Curve in One Dosing Interval (AUCTAU)
    Description Data was not collected due to discontinuation of the study/Due to study termination.
    Time Frame Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days

    Outcome Measure Data

    Analysis Population Description
    Data was not collected due to discontinuation of the study/Due to study termination.
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Measure Participants 0 0 0
    12. Secondary Outcome
    Title Trough Observed Plasma Concentration(Ctrough)
    Description Data was not collected due to discontinuation of the study/Due to study termination.
    Time Frame Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.

    Outcome Measure Data

    Analysis Population Description
    Data was not collected due to discontinuation of the study/Due to study termination.
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Measure Participants 0 0 0
    13. Secondary Outcome
    Title End of Infusion Concentration (Ceoinf)
    Description Data was not collected due to discontinuation of the study/Due to study termination.
    Time Frame Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.

    Outcome Measure Data

    Analysis Population Description
    Data was not collected due to discontinuation of the study/Due to study termination.
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Measure Participants 0 0 0
    14. Secondary Outcome
    Title Area Under the Plasma Concentration-time Curve, 0 to Time of Last Quantifiable Concentration (AUC(0-T)
    Description Data was not collected due to discontinuation of the study/Due to study termination.
    Time Frame Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.

    Outcome Measure Data

    Analysis Population Description
    Data was not collected due to discontinuation of the study/Due to study termination.
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    Measure Participants 0 0 0

    Adverse Events

    Time Frame From the start dosing day and up to 100 days after participant's last dose ( up to 3 years).
    Adverse Event Reporting Description
    Arm/Group Title TRT A TRT B TRT D
    Arm/Group Description URE3 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV3 Q2WK URE8 Q4WK+NIV240mg Q2WK
    All Cause Mortality
    TRT A TRT B TRT D
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/6 (100%) 2/4 (50%) 93/150 (62%)
    Serious Adverse Events
    TRT A TRT B TRT D
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/6 (50%) 3/4 (75%) 86/150 (57.3%)
    Blood and lymphatic system disorders
    Anaemia 0/6 (0%) 0/4 (0%) 2/150 (1.3%)
    Febrile neutropenia 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Cardiac disorders
    Atrial fibrillation 0/6 (0%) 0/4 (0%) 2/150 (1.3%)
    Atrial flutter 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Atrioventricular block 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Stress cardiomyopathy 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Endocrine disorders
    Diabetes insipidus 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Hypogonadism 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Hypophysitis 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Hypothyroidism 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Gastrointestinal disorders
    Abdominal pain 0/6 (0%) 0/4 (0%) 3/150 (2%)
    Abdominal pain upper 0/6 (0%) 0/4 (0%) 2/150 (1.3%)
    Colitis 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Constipation 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Diarrhoea 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Diverticulum intestinal haemorrhagic 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Enteritis 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Faecaloma 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Ileus 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Lower gastrointestinal haemorrhage 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Vomiting 0/6 (0%) 0/4 (0%) 3/150 (2%)
    General disorders
    Asthenia 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Fatigue 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    General physical health deterioration 1/6 (16.7%) 0/4 (0%) 4/150 (2.7%)
    Hyperthermia 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Hypothermia 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Pain 0/6 (0%) 0/4 (0%) 4/150 (2.7%)
    Pelvic mass 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Pyrexia 0/6 (0%) 0/4 (0%) 5/150 (3.3%)
    Sudden death 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Hepatobiliary disorders
    Autoimmune hepatitis 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Bile duct stenosis 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Immune system disorders
    Contrast media reaction 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Drug hypersensitivity 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Haemophagocytic lymphohistiocytosis 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Infections and infestations
    Bacteraemia 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Bronchitis 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Cellulitis 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Device related infection 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Erysipelas 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Lung infection 0/6 (0%) 0/4 (0%) 3/150 (2%)
    Pneumonia 0/6 (0%) 0/4 (0%) 4/150 (2.7%)
    Pneumonia haemophilus 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Urinary tract infection 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Injury, poisoning and procedural complications
    Lumbar vertebral fracture 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Tracheal obstruction 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Investigations
    Alanine aminotransferase increased 0/6 (0%) 0/4 (0%) 2/150 (1.3%)
    Aspartate aminotransferase increased 0/6 (0%) 0/4 (0%) 2/150 (1.3%)
    Blood alkaline phosphatase increased 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Blood bilirubin increased 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Gamma-glutamyltransferase increased 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Metabolism and nutrition disorders
    Dehydration 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Diabetes mellitus 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Diabetic ketoacidosis 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Failure to thrive 0/6 (0%) 0/4 (0%) 3/150 (2%)
    Gout 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Hypercalcaemia 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Hypoglycaemia 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Pain in extremity 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Abdominal neoplasm 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Basal cell carcinoma 0/6 (0%) 0/4 (0%) 2/150 (1.3%)
    Cancer pain 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Malignant neoplasm progression 1/6 (16.7%) 1/4 (25%) 37/150 (24.7%)
    Metastases to central nervous system 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Metastases to lymph nodes 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Squamous cell carcinoma 0/6 (0%) 1/4 (25%) 3/150 (2%)
    Tumour haemorrhage 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Tumour pain 0/6 (0%) 0/4 (0%) 3/150 (2%)
    Nervous system disorders
    Ataxia 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Central nervous system lesion 0/6 (0%) 1/4 (25%) 0/150 (0%)
    Cerebral haematoma 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Cerebrovascular accident 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Dizziness 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Monoplegia 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Paraparesis 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Seizure 0/6 (0%) 0/4 (0%) 3/150 (2%)
    Syncope 0/6 (0%) 0/4 (0%) 3/150 (2%)
    Psychiatric disorders
    Confusional state 0/6 (0%) 1/4 (25%) 1/150 (0.7%)
    Mental status changes 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Persistent depressive disorder 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Renal and urinary disorders
    Acute kidney injury 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Haematuria 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Hydronephrosis 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Urinary tract obstruction 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Respiratory, thoracic and mediastinal disorders
    Aspiration 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Dyspnoea 0/6 (0%) 0/4 (0%) 2/150 (1.3%)
    Haemoptysis 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Hydrothorax 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Hypoxia 0/6 (0%) 0/4 (0%) 2/150 (1.3%)
    Obstructive airways disorder 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Pharyngeal haemorrhage 0/6 (0%) 0/4 (0%) 2/150 (1.3%)
    Pleural effusion 0/6 (0%) 0/4 (0%) 4/150 (2.7%)
    Pneumonia aspiration 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Pneumonitis 0/6 (0%) 0/4 (0%) 3/150 (2%)
    Pulmonary embolism 0/6 (0%) 0/4 (0%) 3/150 (2%)
    Pulmonary haemorrhage 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Respiratory failure 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Vascular disorders
    Embolism 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Extremity necrosis 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Peripheral ischaemia 0/6 (0%) 0/4 (0%) 1/150 (0.7%)
    Other (Not Including Serious) Adverse Events
    TRT A TRT B TRT D
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/6 (100%) 4/4 (100%) 147/150 (98%)
    Blood and lymphatic system disorders
    Anaemia 3/6 (50%) 1/4 (25%) 47/150 (31.3%)
    Neutropenia 0/6 (0%) 0/4 (0%) 8/150 (5.3%)
    Endocrine disorders
    Adrenal insufficiency 1/6 (16.7%) 0/4 (0%) 2/150 (1.3%)
    Hypothyroidism 0/6 (0%) 1/4 (25%) 16/150 (10.7%)
    Eye disorders
    Dry eye 0/6 (0%) 1/4 (25%) 5/150 (3.3%)
    Lacrimation increased 0/6 (0%) 1/4 (25%) 2/150 (1.3%)
    Vision blurred 2/6 (33.3%) 0/4 (0%) 2/150 (1.3%)
    Gastrointestinal disorders
    Abdominal discomfort 0/6 (0%) 1/4 (25%) 0/150 (0%)
    Abdominal distension 1/6 (16.7%) 0/4 (0%) 6/150 (4%)
    Abdominal pain 2/6 (33.3%) 1/4 (25%) 19/150 (12.7%)
    Abdominal pain upper 1/6 (16.7%) 0/4 (0%) 6/150 (4%)
    Anal incontinence 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Ascites 0/6 (0%) 1/4 (25%) 0/150 (0%)
    Constipation 1/6 (16.7%) 0/4 (0%) 31/150 (20.7%)
    Dental caries 0/6 (0%) 1/4 (25%) 0/150 (0%)
    Diarrhoea 5/6 (83.3%) 0/4 (0%) 32/150 (21.3%)
    Dry mouth 1/6 (16.7%) 0/4 (0%) 8/150 (5.3%)
    Dysphagia 2/6 (33.3%) 1/4 (25%) 6/150 (4%)
    Gastritis 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Gastrooesophageal reflux disease 0/6 (0%) 1/4 (25%) 3/150 (2%)
    Lip swelling 0/6 (0%) 1/4 (25%) 0/150 (0%)
    Melaena 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Nausea 3/6 (50%) 0/4 (0%) 37/150 (24.7%)
    Vomiting 3/6 (50%) 0/4 (0%) 26/150 (17.3%)
    General disorders
    Asthenia 1/6 (16.7%) 1/4 (25%) 16/150 (10.7%)
    Chills 0/6 (0%) 0/4 (0%) 14/150 (9.3%)
    Fatigue 4/6 (66.7%) 2/4 (50%) 61/150 (40.7%)
    Gait disturbance 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Oedema peripheral 1/6 (16.7%) 0/4 (0%) 25/150 (16.7%)
    Performance status decreased 0/6 (0%) 1/4 (25%) 1/150 (0.7%)
    Pyrexia 4/6 (66.7%) 1/4 (25%) 29/150 (19.3%)
    Hepatobiliary disorders
    Hepatic haemorrhage 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Infections and infestations
    Gastroenteritis 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Gingivitis 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Localised infection 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Nasopharyngitis 0/6 (0%) 1/4 (25%) 6/150 (4%)
    Pneumonia 1/6 (16.7%) 0/4 (0%) 4/150 (2.7%)
    Upper respiratory tract infection 1/6 (16.7%) 0/4 (0%) 12/150 (8%)
    Urinary tract infection 1/6 (16.7%) 0/4 (0%) 12/150 (8%)
    Injury, poisoning and procedural complications
    Fall 1/6 (16.7%) 1/4 (25%) 8/150 (5.3%)
    Infusion related reaction 0/6 (0%) 1/4 (25%) 2/150 (1.3%)
    Skin abrasion 0/6 (0%) 1/4 (25%) 1/150 (0.7%)
    Sunburn 0/6 (0%) 1/4 (25%) 1/150 (0.7%)
    Investigations
    Alanine aminotransferase increased 2/6 (33.3%) 0/4 (0%) 26/150 (17.3%)
    Amylase increased 0/6 (0%) 0/4 (0%) 13/150 (8.7%)
    Aspartate aminotransferase increased 0/6 (0%) 0/4 (0%) 26/150 (17.3%)
    Blood alkaline phosphatase increased 2/6 (33.3%) 0/4 (0%) 20/150 (13.3%)
    Blood creatinine increased 1/6 (16.7%) 0/4 (0%) 8/150 (5.3%)
    Blood thyroid stimulating hormone increased 0/6 (0%) 1/4 (25%) 4/150 (2.7%)
    Blood uric acid decreased 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Gamma-glutamyltransferase increased 2/6 (33.3%) 0/4 (0%) 18/150 (12%)
    Lipase increased 1/6 (16.7%) 0/4 (0%) 17/150 (11.3%)
    Lymphocyte count decreased 2/6 (33.3%) 0/4 (0%) 7/150 (4.7%)
    Neutrophil count decreased 1/6 (16.7%) 0/4 (0%) 3/150 (2%)
    Platelet count decreased 1/6 (16.7%) 0/4 (0%) 8/150 (5.3%)
    Weight decreased 1/6 (16.7%) 0/4 (0%) 18/150 (12%)
    Metabolism and nutrition disorders
    Decreased appetite 2/6 (33.3%) 1/4 (25%) 24/150 (16%)
    Dehydration 1/6 (16.7%) 0/4 (0%) 4/150 (2.7%)
    Hypercalcaemia 0/6 (0%) 0/4 (0%) 8/150 (5.3%)
    Hyperglycaemia 0/6 (0%) 0/4 (0%) 14/150 (9.3%)
    Hyperkalaemia 1/6 (16.7%) 0/4 (0%) 11/150 (7.3%)
    Hypermagnesaemia 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Hyperuricaemia 1/6 (16.7%) 0/4 (0%) 2/150 (1.3%)
    Hypoalbuminaemia 0/6 (0%) 0/4 (0%) 12/150 (8%)
    Hypokalaemia 0/6 (0%) 1/4 (25%) 9/150 (6%)
    Hypomagnesaemia 1/6 (16.7%) 0/4 (0%) 4/150 (2.7%)
    Hyponatraemia 0/6 (0%) 0/4 (0%) 14/150 (9.3%)
    Hypophosphataemia 2/6 (33.3%) 0/4 (0%) 16/150 (10.7%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/6 (0%) 2/4 (50%) 17/150 (11.3%)
    Back pain 0/6 (0%) 0/4 (0%) 23/150 (15.3%)
    Flank pain 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Joint range of motion decreased 0/6 (0%) 1/4 (25%) 1/150 (0.7%)
    Muscular weakness 2/6 (33.3%) 1/4 (25%) 5/150 (3.3%)
    Musculoskeletal pain 0/6 (0%) 0/4 (0%) 11/150 (7.3%)
    Myalgia 0/6 (0%) 1/4 (25%) 15/150 (10%)
    Neck pain 0/6 (0%) 1/4 (25%) 6/150 (4%)
    Pain in extremity 0/6 (0%) 0/4 (0%) 15/150 (10%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Squamous cell carcinoma 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Nervous system disorders
    Balance disorder 0/6 (0%) 1/4 (25%) 1/150 (0.7%)
    Carotid artery occlusion 0/6 (0%) 1/4 (25%) 0/150 (0%)
    Cognitive disorder 0/6 (0%) 1/4 (25%) 1/150 (0.7%)
    Dizziness 1/6 (16.7%) 0/4 (0%) 13/150 (8.7%)
    Headache 4/6 (66.7%) 0/4 (0%) 23/150 (15.3%)
    Peripheral motor neuropathy 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Peripheral sensory neuropathy 1/6 (16.7%) 0/4 (0%) 3/150 (2%)
    Restless legs syndrome 0/6 (0%) 1/4 (25%) 1/150 (0.7%)
    Sciatica 0/6 (0%) 1/4 (25%) 0/150 (0%)
    Sinus headache 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Psychiatric disorders
    Anxiety 0/6 (0%) 0/4 (0%) 11/150 (7.3%)
    Depression 1/6 (16.7%) 0/4 (0%) 3/150 (2%)
    Insomnia 0/6 (0%) 0/4 (0%) 11/150 (7.3%)
    Renal and urinary disorders
    Dysuria 1/6 (16.7%) 0/4 (0%) 3/150 (2%)
    Pollakiuria 1/6 (16.7%) 0/4 (0%) 6/150 (4%)
    Respiratory, thoracic and mediastinal disorders
    Cough 2/6 (33.3%) 0/4 (0%) 33/150 (22%)
    Dyspnoea 2/6 (33.3%) 0/4 (0%) 26/150 (17.3%)
    Nasal congestion 1/6 (16.7%) 0/4 (0%) 6/150 (4%)
    Rhinitis allergic 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Skin and subcutaneous tissue disorders
    Actinic keratosis 1/6 (16.7%) 1/4 (25%) 5/150 (3.3%)
    Drug eruption 1/6 (16.7%) 0/4 (0%) 2/150 (1.3%)
    Dry skin 0/6 (0%) 0/4 (0%) 13/150 (8.7%)
    Hyperkeratosis 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Lichen planus 1/6 (16.7%) 0/4 (0%) 0/150 (0%)
    Pruritus 0/6 (0%) 2/4 (50%) 22/150 (14.7%)
    Rash 0/6 (0%) 1/4 (25%) 16/150 (10.7%)
    Rash macular 1/6 (16.7%) 0/4 (0%) 2/150 (1.3%)
    Rash maculo-papular 0/6 (0%) 2/4 (50%) 9/150 (6%)
    Rash papular 0/6 (0%) 1/4 (25%) 0/150 (0%)
    Rash pruritic 1/6 (16.7%) 0/4 (0%) 2/150 (1.3%)
    Skin ulcer 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Vascular disorders
    Hot flush 1/6 (16.7%) 0/4 (0%) 1/150 (0.7%)
    Hypertension 2/6 (33.3%) 0/4 (0%) 3/150 (2%)
    Hypotension 1/6 (16.7%) 0/4 (0%) 6/150 (4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Bristol-Myers Squibb Study Director
    Organization Bristol-Myers Squibb
    Phone Please email
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT02253992
    Other Study ID Numbers:
    • CA186-107
    • 2014-002241-22
    First Posted:
    Oct 1, 2014
    Last Update Posted:
    Oct 5, 2020
    Last Verified:
    Sep 1, 2020