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    Clinical Trial Results:
    A Randomized Open-Label Phase 1/2 Study of INCB001158 Combined With Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, in Participants With Relapsed or Refractory Multiple Myeloma

    Summary
    EudraCT number
    		 2018-004076-35
    Trial protocol
    		 ES  
    Global end of trial date
    05 Apr 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    05 Apr 2023
    First version publication date
    05 Apr 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    INCB 01158-206
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Incyte Corporation
    Sponsor organisation address
    1801 Augustine Cutoff Drive, Wilmington, United States, 19803
    Public contact
    Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.com
    Scientific contact
    Study Director, Incyte Corporation, 1 8554633463, medinfo@incyte.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    05 Apr 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Apr 2022
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The purpose of this study was to evaluate the safety and antitumor activity of INCB001158 in combination with daratumumab subcutaneous (SC), compared with daratumumab SC alone, in participants with relapsed or refractory multiple myeloma.
    Protection of trial subjects
    This study was to be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and conducted in adherence to the study Protocol, applicable Good Clinical Practices, and applicable laws and country-specific regulations in which the study is being conducted.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Sep 2019
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy
    Long term follow-up duration
    		 3 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    United States: 5
    Worldwide total number of subjects
    15
    EEA total number of subjects
    10
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    7
    From 65 to 84 years
    7
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This study was conducted at 11 study centers in Germany, Spain, and the United States.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Phase 1: INCB001158 75 mg BID + daratumumab
    Arm description
    		 In Phase 1, participants received oral INCB001158 75 milligrams (mg) twice daily (BID) in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.
    Arm type
    		 Experimental

    Investigational medicinal product name
    daratumumab SC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    120 mg/mL daratumumab + 20 μg/mL rHuPH20 solution

    Investigational medicinal product name
    INCB001158
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg and 100 mg tablets

    Arm title
    		 Phase 1: INCB001158 100 mg BID + daratumumab
    Arm description
    		 In Phase 1, participants received oral INCB001158 100 mg BID in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.
    Arm type
    		 Experimental

    Investigational medicinal product name
    daratumumab SC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    120 mg/mL daratumumab + 20 μg/mL rHuPH20 solution

    Investigational medicinal product name
    INCB001158
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg and 100 mg tablets

    Arm title
    		 Phase 2: INCB001158 100 mg BID + daratumumab
    Arm description
    		 In Phase 1, participants received oral INCB001158 100 mg BID in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.
    Arm type
    		 Experimental

    Investigational medicinal product name
    daratumumab SC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    120 mg/mL daratumumab + 20 μg/mL rHuPH20 solution

    Investigational medicinal product name
    INCB001158
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg and 100 mg tablets

    Arm title
    		 Phase 2: daratumumab; cross over to INCB001158 + daratumumab
    Arm description
    		 In Part 1 of Phase 2, participants received daratumumb 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2 (28-day cycles), once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. At the time of confirmed disease progression, participants crossed over to Part 2 of Phase 2 to receive oral INCB001158 100 mg BID starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment in Phase 2 continued for as long as participants were receiving clinical benefit and did not met any criteria for study withdrawal.
    Arm type
    		 Experimental

    Investigational medicinal product name
    daratumumab SC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    120 mg/mL daratumumab + 20 μg/mL rHuPH20 solution

    Investigational medicinal product name
    INCB001158
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg and 100 mg tablets

    Arm title
    		 Phase 2: INCB001158; cross over to INCB001158 + daratumumab
    Arm description
    		 In Part 1 of Phase 2, participants received oral INCB001158 100 mg BID in 28-day cycles starting at Cycle 1. At the time of confirmed disease progression, participants crossed over to Part 2 of Part 2 to receive oral INCB001158 100 mg BID starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment in Phase 2 continued for as long as participants were receiving clinical benefit and did not met any criteria for study withdrawal.
    Arm type
    		 Experimental

    Investigational medicinal product name
    daratumumab SC
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    120 mg/mL daratumumab + 20 μg/mL rHuPH20 solution

    Investigational medicinal product name
    INCB001158
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    25 mg and 100 mg tablets

    Number of subjects in period 1
    		Phase 1: INCB001158 75 mg BID + daratumumab Phase 1: INCB001158 100 mg BID + daratumumab Phase 2: INCB001158 100 mg BID + daratumumab Phase 2: daratumumab; cross over to INCB001158 + daratumumab Phase 2: INCB001158; cross over to INCB001158 + daratumumab
    Started
    6
    4
    2
    1
    2
    Completed
    1
    2
    2
    0
    1
    Not completed
    5
    2
    0
    1
    1
         Adverse event, serious fatal
    5
    2
    -
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Phase 1: INCB001158 75 mg BID + daratumumab
    Reporting group description
    		 In Phase 1, participants received oral INCB001158 75 milligrams (mg) twice daily (BID) in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.

    Reporting group title
    Phase 1: INCB001158 100 mg BID + daratumumab
    Reporting group description
    		 In Phase 1, participants received oral INCB001158 100 mg BID in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.

    Reporting group title
    Phase 2: INCB001158 100 mg BID + daratumumab
    Reporting group description
    		 In Phase 1, participants received oral INCB001158 100 mg BID in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.

    Reporting group title
    Phase 2: daratumumab; cross over to INCB001158 + daratumumab
    Reporting group description
    		 In Part 1 of Phase 2, participants received daratumumb 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2 (28-day cycles), once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. At the time of confirmed disease progression, participants crossed over to Part 2 of Phase 2 to receive oral INCB001158 100 mg BID starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment in Phase 2 continued for as long as participants were receiving clinical benefit and did not met any criteria for study withdrawal.

    Reporting group title
    Phase 2: INCB001158; cross over to INCB001158 + daratumumab
    Reporting group description
    		 In Part 1 of Phase 2, participants received oral INCB001158 100 mg BID in 28-day cycles starting at Cycle 1. At the time of confirmed disease progression, participants crossed over to Part 2 of Part 2 to receive oral INCB001158 100 mg BID starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment in Phase 2 continued for as long as participants were receiving clinical benefit and did not met any criteria for study withdrawal.

    Reporting group values
    		 Phase 1: INCB001158 75 mg BID + daratumumab Phase 1: INCB001158 100 mg BID + daratumumab Phase 2: INCB001158 100 mg BID + daratumumab Phase 2: daratumumab; cross over to INCB001158 + daratumumab Phase 2: INCB001158; cross over to INCB001158 + daratumumab Total
    Number of subjects
    		 6 4 2 1 2 15
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 3 2 1 0 1 7
        From 65-84 years
    		 3 2 1 1 0 7
        85 years and over
    		 0 0 0 0 1 1
    Age Continuous
    100=To protect participant privacy, a mean age and standard deviation are not reported for a single participant.
    Units: years
        arithmetic mean (standard deviation)
    		 65.0 ( 11.70 ) 68.0 ( 9.83 ) 67.0 ( 12.73 ) 100 ( 100 ) 71.5 ( 19.09 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 2 2 1 0 0 5
        Male
    		 4 2 1 1 2 10
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0
        Asian
    		 0 0 0 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0
        Black or African American
    		 1 0 0 0 0 1
        White
    		 5 4 2 1 2 14
        More than one race
    		 0 0 0 0 0 0
        Unknown or Not Reported
    		 0 0 0 0 0 0
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 0 0 0 0 1 1
        Not Hispanic or Latino
    		 6 4 2 1 1 14
        Unknown or Not Reported
    		 0 0 0 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    Phase 1: INCB001158 75 mg BID + daratumumab
    Reporting group description
    		 In Phase 1, participants received oral INCB001158 75 milligrams (mg) twice daily (BID) in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.

    Reporting group title
    Phase 1: INCB001158 100 mg BID + daratumumab
    Reporting group description
    		 In Phase 1, participants received oral INCB001158 100 mg BID in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.

    Reporting group title
    Phase 2: INCB001158 100 mg BID + daratumumab
    Reporting group description
    		 In Phase 1, participants received oral INCB001158 100 mg BID in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.

    Reporting group title
    Phase 2: daratumumab; cross over to INCB001158 + daratumumab
    Reporting group description
    		 In Part 1 of Phase 2, participants received daratumumb 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2 (28-day cycles), once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. At the time of confirmed disease progression, participants crossed over to Part 2 of Phase 2 to receive oral INCB001158 100 mg BID starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment in Phase 2 continued for as long as participants were receiving clinical benefit and did not met any criteria for study withdrawal.

    Reporting group title
    Phase 2: INCB001158; cross over to INCB001158 + daratumumab
    Reporting group description
    		 In Part 1 of Phase 2, participants received oral INCB001158 100 mg BID in 28-day cycles starting at Cycle 1. At the time of confirmed disease progression, participants crossed over to Part 2 of Part 2 to receive oral INCB001158 100 mg BID starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment in Phase 2 continued for as long as participants were receiving clinical benefit and did not met any criteria for study withdrawal.

    Primary: Phase 1: Number of participants with any treatment-emergent adverse event (TEAE)

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    End point title
    		 Phase 1: Number of participants with any treatment-emergent adverse event (TEAE) [1] [2]
    End point description
    A TEAE was defined as an adverse event (AE) that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.
    End point type
    Primary
    End point timeframe
    up to 454 days
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not conducted for this endpoint.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Phase 1: INCB001158 75 mg BID + daratumumab Phase 1: INCB001158 100 mg BID + daratumumab
    Number of subjects analysed
    6
    4
    Units: participants
    6
    4
    No statistical analyses for this end point

    Primary: Phase 2: Overall Response Rate (ORR): number of participants with a documented response of complete response (CR), stringent CR (sCR), very good partial response (VGPR), or PR, as per International Myeloma Working Group (IMWG) criteria

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    End point title
    		 Phase 2: Overall Response Rate (ORR): number of participants with a documented response of complete response (CR), stringent CR (sCR), very good partial response (VGPR), or PR, as per International Myeloma Working Group (IMWG) criteria [3] [4]
    End point description
    CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, <5% bone marrow plasma cells (PCs). sCR: defined CR, plus (a) normal free light chain (FLC) ratio, (b) no clonal PCs by immunohistochemistry, immunofluorescence, or 2- to 4-color flow cytometry. VGPR: serum/urine M-component detectable by immunofixation but not on electrophoresis, or ≥90% reduction in serum M-protein (SMP) plus urine M-protein (UMP) <100 milligrams (mg)/24 hours. PR: ≥50% reduction of SMP and reduction in 24-hour UMP by ≥90% or to <200 mg/24 hours. SMP and UMP not measurable: decrease of ≥50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. SMP and UMP not measurable, and serum free light assay is not measurable: ≥50% reduction in bone marrow PCs is required in place of M-protein, if Baseline bone marrow PC percentage was ≥30%. If present at Baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is required.
    End point type
    Primary
    End point timeframe
    up to Day 386
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Statistical analysis was not conducted for this endpoint.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Phase 2: INCB001158 100 mg BID + daratumumab Phase 2: daratumumab; cross over to INCB001158 + daratumumab Phase 2: INCB001158; cross over to INCB001158 + daratumumab
    Number of subjects analysed
    2
    1
    2
    Units: participants
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Phase 1: ORR: number of participants with a documented response of CR, sCR, VGPR, or PR, as per IMWG criteria

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    End point title
    		 Phase 1: ORR: number of participants with a documented response of CR, sCR, VGPR, or PR, as per IMWG criteria [5]
    End point description
    CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, <5% bone marrow plasma cells (PCs). sCR: defined CR, plus (a) normal free light chain (FLC) ratio, (b) no clonal PCs by immunohistochemistry, immunofluorescence, or 2- to 4-color flow cytometry. VGPR: serum/urine M-component detectable by immunofixation but not on electrophoresis, or ≥90% reduction in serum M-protein (SMP) plus urine M-protein (UMP) <100 milligrams (mg)/24 hours. PR: ≥50% reduction of SMP and reduction in 24-hour UMP by ≥90% or to <200 mg/24 hours. SMP and UMP not measurable: decrease of ≥50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. SMP and UMP not measurable, and serum free light assay is not measurable: ≥50% reduction in bone marrow PCs is required in place of M-protein, if Baseline bone marrow PC percentage was ≥30%. If present at Baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is required.
    End point type
    Secondary
    End point timeframe
    up to Day 395
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Phase 1: INCB001158 75 mg BID + daratumumab Phase 1: INCB001158 100 mg BID + daratumumab
    Number of subjects analysed
    6
    4
    Units: participants
    0
    0
    No statistical analyses for this end point

    Secondary: Phase 2: Number of participants with any TEAE

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    End point title
    		 Phase 2: Number of participants with any TEAE [6]
    End point description
    A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.
    End point type
    Secondary
    End point timeframe
    up to 420 days
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Phase 2: INCB001158 100 mg BID + daratumumab Phase 2: daratumumab; cross over to INCB001158 + daratumumab Phase 2: INCB001158; cross over to INCB001158 + daratumumab
    Number of subjects analysed
    2
    1
    2
    Units: participants
    1
    1
    1
    No statistical analyses for this end point

    Secondary: Phase 1: Time to response, defined as the time from the first dose of study drug to the first documented response of PR or better (CR, sCR, VGPR, or PR), as per IMWG criteria

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    End point title
    		 Phase 1: Time to response, defined as the time from the first dose of study drug to the first documented response of PR or better (CR, sCR, VGPR, or PR), as per IMWG criteria [7]
    End point description
    CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, <5% bone marrow plasma cells (PCs). sCR: defined CR, plus (a) normal free light chain (FLC) ratio, (b) no clonal PCs by immunohistochemistry, immunofluorescence, or 2- to 4-color flow cytometry. VGPR: serum/urine M-component detectable by immunofixation but not on electrophoresis, or ≥90% reduction in serum M-protein (SMP) plus urine M-protein (UMP) <100 milligrams (mg)/24 hours. PR: ≥50% reduction of SMP and reduction in 24-hour UMP by ≥90% or to <200 mg/24 hours. SMP and UMP not measurable: decrease of ≥50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. SMP and UMP not measurable, and serum free light assay is not measurable: ≥50% reduction in bone marrow PCs is required in place of M-protein, if Baseline bone marrow PC percentage was ≥30%. If present at Baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is required.
    End point type
    Secondary
    End point timeframe
    up to Day 395
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Phase 1: INCB001158 75 mg BID + daratumumab Phase 1: INCB001158 100 mg BID + daratumumab
    Number of subjects analysed
    0 [8]
    0 [9]
    Units: days
        median (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [8] - No participants had a response of PR or better; thus, analysis was not conducted.
    [9] - No participants had a response of PR or better; thus, analysis was not conducted.
    No statistical analyses for this end point

    Secondary: Phase 2: Time to response, defined as the time from the first dose of study drug to the first documented response of PR or better (CR, sCR, VGPR, or PR), as per IMWG criteria

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    End point title
    		 Phase 2: Time to response, defined as the time from the first dose of study drug to the first documented response of PR or better (CR, sCR, VGPR, or PR), as per IMWG criteria [10]
    End point description
    CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, <5% bone marrow plasma cells (PCs). sCR: defined CR, plus (a) normal free light chain (FLC) ratio, (b) no clonal PCs by immunohistochemistry, immunofluorescence, or 2- to 4-color flow cytometry. VGPR: serum/urine M-component detectable by immunofixation but not on electrophoresis, or ≥90% reduction in serum M-protein (SMP) plus urine M-protein (UMP) <100 milligrams (mg)/24 hours. PR: ≥50% reduction of SMP and reduction in 24-hour UMP by ≥90% or to <200 mg/24 hours. SMP and UMP not measurable: decrease of ≥50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. SMP and UMP not measurable, and serum free light assay is not measurable: ≥50% reduction in bone marrow PCs is required in place of M-protein, if Baseline bone marrow PC percentage was ≥30%. If present at Baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is required.
    End point type
    Secondary
    End point timeframe
    up to Day 386
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Phase 2: INCB001158 100 mg BID + daratumumab Phase 2: daratumumab; cross over to INCB001158 + daratumumab Phase 2: INCB001158; cross over to INCB001158 + daratumumab
    Number of subjects analysed
    0 [11]
    0 [12]
    0 [13]
    Units: days
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [11] - No participants had a response of PR or better; thus, analysis was not conducted.
    [12] - No participants had a response of PR or better; thus, analysis was not conducted
    [13] - No participants had a response of PR or better; thus, analysis was not conducted
    No statistical analyses for this end point

    Secondary: Phase 2: Duration of response, defined as time from first documented response of PR or better (CR, sCR, VGPR, PR), as per IMWG criteria, until date of disease progression or death, whichever occurred first

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    End point title
    		 Phase 2: Duration of response, defined as time from first documented response of PR or better (CR, sCR, VGPR, PR), as per IMWG criteria, until date of disease progression or death, whichever occurred first [14]
    End point description
    CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, <5% bone marrow plasma cells (PCs). sCR: defined CR, plus (a) normal free light chain (FLC) ratio, (b) no clonal PCs by immunohistochemistry, immunofluorescence, or 2- to 4-color flow cytometry. VGPR: serum/urine M-component detectable by immunofixation but not on electrophoresis, or ≥90% reduction in serum M-protein (SMP) plus urine M-protein (UMP) <100 milligrams (mg)/24 hours. PR: ≥50% reduction of SMP and reduction in 24-hour UMP by ≥90% or to <200 mg/24 hours. SMP and UMP not measurable: decrease of ≥50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. SMP and UMP not measurable, and serum free light assay is not measurable: ≥50% reduction in bone marrow PCs is required in place of M-protein, if Baseline bone marrow PC percentage was ≥30%. If present at Baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is required.
    End point type
    Secondary
    End point timeframe
    up to Day 386
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Phase 2: INCB001158 100 mg BID + daratumumab Phase 2: daratumumab; cross over to INCB001158 + daratumumab Phase 2: INCB001158; cross over to INCB001158 + daratumumab
    Number of subjects analysed
    0 [15]
    0 [16]
    0 [17]
    Units: days
        median (confidence interval 95%)
    ( to )
    ( to )
    ( to )
    Notes
    [15] - No participants had a response of PR or better; thus, analysis was not conducted.
    [16] - No participants had a response of PR or better; thus, analysis was not conducted.
    [17] - No participants had a response of PR or better; thus, analysis was not conducted.
    No statistical analyses for this end point

    Secondary: Phase 1: Duration of response, defined as time from first documented response of PR or better (CR, sCR, VGPR, PR), as per IMWG criteria, until date of disease progression or death, whichever occurred first

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    End point title
    		 Phase 1: Duration of response, defined as time from first documented response of PR or better (CR, sCR, VGPR, PR), as per IMWG criteria, until date of disease progression or death, whichever occurred first [18]
    End point description
    CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, <5% bone marrow plasma cells (PCs). sCR: defined CR, plus (a) normal free light chain (FLC) ratio, (b) no clonal PCs by immunohistochemistry, immunofluorescence, or 2- to 4-color flow cytometry. VGPR: serum/urine M-component detectable by immunofixation but not on electrophoresis, or ≥90% reduction in serum M-protein (SMP) plus urine M-protein (UMP) <100 milligrams (mg)/24 hours. PR: ≥50% reduction of SMP and reduction in 24-hour UMP by ≥90% or to <200 mg/24 hours. SMP and UMP not measurable: decrease of ≥50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. SMP and UMP not measurable, and serum free light assay is not measurable: ≥50% reduction in bone marrow PCs is required in place of M-protein, if Baseline bone marrow PC percentage was ≥30%. If present at Baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is required.
    End point type
    Secondary
    End point timeframe
    up to Day 395
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Phase 1: INCB001158 75 mg BID + daratumumab Phase 1: INCB001158 100 mg BID + daratumumab
    Number of subjects analysed
    0 [19]
    0 [20]
    Units: days
        median (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [19] - No participants had a response of PR or better; thus, analysis was not conducted
    [20] - No participants had a response of PR or better; thus, analysis was not conducted
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS), defined as the duration from the date of the first dose of study drug until either progressive disease, as per IMWG criteria, or death, whichever occurred first

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    End point title
    		 Progression-free survival (PFS), defined as the duration from the date of the first dose of study drug until either progressive disease, as per IMWG criteria, or death, whichever occurred first
    End point description
    Progressive disease: increase of 25% from the lowest response value in any one of the following: (a) serum M-component (absolute increase must be ≥0.5 grams per deciliter [g/dL]); (b) urine M-component (absolute increase must be ≥200 mg/24 hours); (c) only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); (d) only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cell (PC) percentage (absolute percentage must be ≥10%); (d) bone marrow PC percentage: the absolute percentage must be > 10%; (e) definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; (f) development of hypercalcemia (corrected serum calcium > 11.5 mg/dL) that can be attributed solely to the PC proliferative disorder.
    End point type
    Secondary
    End point timeframe
    up to approximately 2 years
    End point values
    		 Phase 1: INCB001158 75 mg BID + daratumumab Phase 1: INCB001158 100 mg BID + daratumumab Phase 2: INCB001158 100 mg BID + daratumumab Phase 2: daratumumab; cross over to INCB001158 + daratumumab Phase 2: INCB001158; cross over to INCB001158 + daratumumab
    Number of subjects analysed
    6 [21]
    4 [22]
    2 [23]
    1 [24]
    2 [25]
    Units: days
        Minimum value, uncensored
    8
    26
    9999
    9999
    9999
        Maximum value, uncensored
    337
    169
    9999
    9999
    9999
    Notes
    [21] - PFS was calculated for individual participants; no formal analysis due to a small sample size.
    [22] - PFS was calculated for individual participants; no formal analysis due to a small sample size.
    [23] - Data cannot be reported; the small sample size could lead to the re-identification of participants.
    [24] - Data cannot be reported; the small sample size could lead to the re-identification of participants.
    [25] - Data cannot be reported; the small sample size could lead to the re-identification of participants.
    No statistical analyses for this end point

    Secondary: Phase 1: Minimal residual disease (MRD), defined as the percentage of MRD-negative participants

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    End point title
    		 Phase 1: Minimal residual disease (MRD), defined as the percentage of MRD-negative participants [26]
    End point description
    Bone marrow aspirate was to be collected for MRD analysis. The MRD assay required an analysis to be performed at Baseline and another analysis to be performed at the time of suspected complete response. At the time enrollment was halted, no participants had a complete response; thus, MRD analysis was not performed.
    End point type
    Secondary
    End point timeframe
    up to approximately 2 years
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Phase 1: INCB001158 75 mg BID + daratumumab Phase 1: INCB001158 100 mg BID + daratumumab
    Number of subjects analysed
    0 [27]
    0 [28]
    Units: percentage of participants
    Notes
    [27] - Analysis was not conducted; no participants had a complete response at time of enrollment halt.
    [28] - Analysis was not conducted; no participants had a complete response at time of enrollment halt.
    No statistical analyses for this end point

    Secondary: Phase 2: MRD, defined as the percentage of MRD-negative participants

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    End point title
    		 Phase 2: MRD, defined as the percentage of MRD-negative participants [29]
    End point description
    Bone marrow aspirate was to be collected for MRD analysis. The MRD assay required an analysis to be performed at Baseline and another analysis to be performed at the time of suspected complete response. At the time enrollment was halted, no participants had a complete response; thus, MRD analysis was not performed.
    End point type
    Secondary
    End point timeframe
    up to approximately 2 years
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Statistical analysis was not conducted for this endpoint.
    End point values
    		 Phase 2: INCB001158 100 mg BID + daratumumab Phase 2: daratumumab; cross over to INCB001158 + daratumumab Phase 2: INCB001158; cross over to INCB001158 + daratumumab
    Number of subjects analysed
    0 [30]
    0 [31]
    0 [32]
    Units: percentage of participants
    Notes
    [30] - Analysis was not conducted; no participants had a complete response at time of enrollment halt.
    [31] - Analysis was not conducted; no participants had a complete response at time of enrollment halt.
    [32] - Analysis was not conducted; no participants had a complete response at time of enrollment halt.
    No statistical analyses for this end point

    Secondary: Overall survival

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    End point title
    		 Overall survival
    End point description
    Overall survival (OS) was defined as the time from the first dose of study drug to death from any cause until study completion. 9999=Minimum and maximum data values cannot be reported; doing so for the small sample size could lead to the re-identification of participants.
    End point type
    Secondary
    End point timeframe
    up to 923 days (approximately 2.5 years)
    End point values
    		 Phase 1: INCB001158 75 mg BID + daratumumab Phase 1: INCB001158 100 mg BID + daratumumab Phase 2: INCB001158 100 mg BID + daratumumab Phase 2: daratumumab; cross over to INCB001158 + daratumumab Phase 2: INCB001158; cross over to INCB001158 + daratumumab
    Number of subjects analysed
    6 [33]
    4 [34]
    2 [35]
    1 [36]
    2 [37]
    Units: days
    number (not applicable)
        Minimum value, uncensored
    113
    127
    9999
    9999
    9999
        Maximum value, uncensored
    766
    604
    9999
    9999
    9999
    Notes
    [33] - OS was calculated for individual participants; no formal analysis due to a small sample size.
    [34] - OS was calculated for individual participants; no formal analysis due to a small sample size.
    [35] - Data cannot be reported; the small sample size could lead to the re-identification of participants.
    [36] - Data cannot be reported; the small sample size could lead to the re-identification of participants.
    [37] - Data cannot be reported; the small sample size could lead to the re-identification of participants.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were assessed for up to 454 days; All-cause Mortality was assessed for up to 923 days (approximately 2.5 years).
    Adverse event reporting additional description
    Treatment-emergent adverse events (TEAEs), defined as adverse events that were reported for the first time or the worsening of pre-existing events after the first dose of study treatment, have been reported.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Phase 1: INCB001158 75 mg BID + daratumumab
    Reporting group description
    		 In Phase 1, participants received oral INCB001158 75 milligrams (mg) twice daily (BID) in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.

    Reporting group title
    Phase 1: INCB001158 100 mg BID + daratumumab
    Reporting group description
    		 In Phase 1, participants received oral INCB001158 100 mg BID in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.

    Reporting group title
    Total
    Reporting group description
    		 Total

    Reporting group title
    Phase 1/2: daratumumab; cross over to INCB001158 + daratumumab
    Reporting group description
    		 In Phase 1, participants received daratumumb 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2 (28-day cycles), once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. At the time of confirmed disease progression, participants crossed over to Phase 2 to receive oral INCB001158 75 or 100 mg BID starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment in Phase 2 continued for as long as participants were receiving clinical benefit and did not met any criteria for study withdrawal.

    Reporting group title
    Phase 1/2: INCB001158; cross over to INCB001158 + daratumumab
    Reporting group description
    		 In Phase 1, participants received oral INCB001158 75 or 100 mg BID in 28-day cycles starting at Cycle 1. At the time of confirmed disease progression, participants crossed over to Part 2 to receive oral INCB001158 75 or 100 mg BID starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment in Phase 2 continued for as long as participants were receiving clinical benefit and did not met any criteria for study withdrawal.

    Reporting group title
    Phase 2: INCB001158 100 mg BID + daratumumab
    Reporting group description
    		 In Phase 1, participants received oral INCB001158 100 mg BID in 28-day cycles starting at Cycle 1, and 1800 mg subcutaneous daratumumab, administered once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and once every 4 weeks thereafter. Treatment continued until disease progression, unacceptable toxicity, or discontinuation from study treatment for any other reason.

    Serious adverse events
    		 Phase 1: INCB001158 75 mg BID + daratumumab Phase 1: INCB001158 100 mg BID + daratumumab Total Phase 1/2: daratumumab; cross over to INCB001158 + daratumumab Phase 1/2: INCB001158; cross over to INCB001158 + daratumumab Phase 2: INCB001158 100 mg BID + daratumumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 6 (50.00%)
    1 / 4 (25.00%)
    5 / 15 (33.33%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         number of deaths (all causes)
    5
    2
    9
    1
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Condition aggravated
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Phase 1: INCB001158 75 mg BID + daratumumab Phase 1: INCB001158 100 mg BID + daratumumab Total Phase 1/2: daratumumab; cross over to INCB001158 + daratumumab Phase 1/2: INCB001158; cross over to INCB001158 + daratumumab Phase 2: INCB001158 100 mg BID + daratumumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    4 / 4 (100.00%)
    13 / 15 (86.67%)
    1 / 1 (100.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    Hypertension
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    4 / 15 (26.67%)
    1 / 1 (100.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    4
    1
    1
    1
    Discomfort
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Fatigue
         subjects affected / exposed
    3 / 6 (50.00%)
    0 / 4 (0.00%)
    4 / 15 (26.67%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    4
    1
    0
    0
    Injection site bruising
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 4 (25.00%)
    3 / 15 (20.00%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    1
    1
    3
    0
    0
    1
    Pyrexia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    2 / 15 (13.33%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    3
    2
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    2 / 15 (13.33%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    0
    Dyspnoea
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    2 / 15 (13.33%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    0
    Lung infiltration
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Nasal congestion
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 4 (0.00%)
    2 / 15 (13.33%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    Productive cough
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    2 / 15 (13.33%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    0
    Pulmonary oedema
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Listless
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Injury, poisoning and procedural complications
    Clavicle fracture
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Humerus fracture
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Rib fracture
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Skin laceration
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Cardiovascular insufficiency
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Nervous system disorders
    Dysaesthesia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Dysstasia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Headache
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    2 / 15 (13.33%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    2
    1
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    0
    4
    0
    0
    4
    Lymphopenia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    3 / 15 (20.00%)
    0 / 1 (0.00%)
    1 / 2 (50.00%)
    1 / 2 (50.00%)
         occurrences all number
    0
    1
    3
    0
    1
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Diarrhoea
         subjects affected / exposed
    3 / 6 (50.00%)
    0 / 4 (0.00%)
    3 / 15 (20.00%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    3
    0
    3
    0
    0
    0
    Dyspepsia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Nausea
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 4 (50.00%)
    2 / 15 (13.33%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    2
    2
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Ingrowing nail
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    Pruritus
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Bone pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    2 / 15 (13.33%)
    0 / 1 (0.00%)
    1 / 2 (50.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    2
    0
    1
    0
    Muscle spasms
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    2 / 15 (13.33%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    0
    Muscular weakness
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Myalgia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Pain in extremity
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Rhinovirus infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    1 / 1 (100.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    0
    Tooth infection
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 4 (0.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    2
    0
    2
    0
    0
    0
    Oroticaciduria
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 4 (25.00%)
    1 / 15 (6.67%)
    0 / 1 (0.00%)
    0 / 2 (0.00%)
    0 / 2 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    11 Mar 2019
    A summary of experimental studies was added to provide evidence to support the biologic rationale for the combination. Updated to allow for 2 cycles of INCB001158 monotherapy instead of 3 cycles in Treatment Group C – Part 1, and to require all participants to have had at least 3 prior treatments. Stopping rules were added for safety in Phase 2. A revision was made to clarify the definition of injection-related reactions (IRRs) and the management of IRRs.
    12 Oct 2020
    The primary purpose of this amendment was to introduce a crossover to INCB001158+daratumumab after daratumumab monotherapy.
    01 Dec 2021
    The primary purpose of this amendment was to provide guidance for the management of ongoing participants, as enrollment had been terminated and sufficient data had been collected for safety analysis.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study was terminated following a recruitment challenge. There were no safety-related concerns.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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