Relapsed or Refractory Multiple Myeloma
Conditions
Keywords
Arginase inhibitor, multiple myeloma, Daratumumab
Brief summary
The purpose of this study is to evaluate the safety and antitumor activity of INCB001158 in combination with daratumumab SC, compared with daratumumab SC alone, in participants with relapsed or refractory multiple myeloma.
Interventions
DRUGINCB001158
Phase 1: INCB001158 administered orally twice daily at the protocol-defined starting dose, with dose escalation/de-escalation based on protocol-defined toxicity criteria to determine the maximum tolerated dose. INCB001158 is administered in combination with daratumumab SC. Phase 2: INCB001158 administered orally at the recommended dose from Phase 1 either as a monotherapy or in combination with daratumumab SC.
BIOLOGICALDaratumumab SC
Daratumumab 1800 mg co-formulated with rHuPH20 (2000 U/mL) and administered subcutaneously once weekly for Cycles 1 and 2, once every 2 weeks for Cycles 3 to 6, and then once every 4 weeks. Daratumumab will be administered either as monotherapy or in combination with INCB001158.
Sponsors
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
An initial equal randomization of participants between INCB001158 in combination with daratumumab SC (Treatment Group A), daratumumab SC monotherapy (Treatment Group B), and INCB001158 monotherapy (Treatment Group C) will be conducted. Participants in the treatment groups B and C at confirmed disease progression will be crossed over to INCB001158 + daratumumab SC. After the equal randomization period, a response adaptive randomization design will be used to compare the objective response rate of Treatment Groups A and B with adjustments to the randomization rate based on the observed objective response rate.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Prior diagnosis of multiple myeloma according to IMWG diagnostic criteria. * Measurable disease at screening. * Has received at least 3 but not more than 5 prior lines of multiple myeloma treatment, including proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapies. * Eastern Cooperative Oncology Group performance status of 0 or 1. * Willing to avoid pregnancy or fathering children. * Willing to provide fresh and archival bone marrow aspiration and biopsy tissue.
Exclusion criteria
* Receipt of any of the following treatment within the indicated interval before the first administration of study drug: * Anti-myeloma treatment within 2 weeks or 5 half-lives (whichever is longer). * Investigational drug (including investigational vaccines) or invasive investigational medical device within 4 weeks. * Autologous stem cell transplant within 12 weeks, or allogeneic stem cell transplant at any time. * Plasmapheresis within 4 weeks. * Radiation therapy within 2 weeks. * Major surgery within 2 weeks, or inadequate recovery from an earlier surgery, or surgery planned during the time the participant is expected to participate in the study or within 2 weeks after the last dose of study treatment. * Toxicity ≥ Grade 2 from previous anti-myeloma therapy except for stable chronic toxicities (≤ Grade 2) not expected to resolve, such as stable Grade 2 peripheral neuropathy. * Known additional malignancy (other than multiple myeloma) that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry. * Laboratory values at screening outside the protocol-defined range. * Significant concurrent, uncontrolled medical condition including but not limited to known chronic obstructive pulmonary disease (COPD), persistent asthma, or history of asthma within the past 2 years; chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment; acute diffuse infiltrative pulmonary disease; clinically significant or uncontrolled cardiac disease. * Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or amyloidosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to 454 days | 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. |
| Phase 2: Overall Response Rate (ORR): Number of Participants With a Documented Response of Complete Response (CR), Very Good Partial Response (VGPR), or PR, as Per International Myeloma Working Group (IMWG) Criteria | up to Day 386 | CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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, VGPR, or PR), as Per IMWG Criteria | up to Day 395 | CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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. |
| 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, VGPR, or PR), as Per IMWG Criteria | up to Day 386 | CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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. |
| Phase 1: Duration of Response, Defined as Time From First Documented Response of PR or Better (CR, VGPR, PR), as Per IMWG Criteria, Until Date of Disease Progression or Death, Whichever Occurred First | up to Day 395 | CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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. |
| Phase 2: Duration of Response, Defined as Time From First Documented Response of PR or Better (CR, VGPR, PR), as Per IMWG Criteria, Until Date of Disease Progression or Death, Whichever Occurred First | up to Day 386 | CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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. |
| Phase 1: ORR: Number of Participants With a Documented Response of CR, VGPR, or PR, as Per IMWG Criteria | up to Day 395 | CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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. |
| Phase 1: Minimal Residual Disease (MRD), Defined as the Percentage of MRD-negative Participants | up to approximately 2 years | Bone marrow aspirate was to be collected for MRD analysis. |
| Phase 2: MRD, Defined as the Percentage of MRD-negative Participants | up to approximately 2 years | Bone marrow aspirate was to be collected for MRD analysis. |
| Overall Survival | up to 923 days (approximately 2.5 years) | Overall survival was defined as the time from the first dose of study drug to death from any cause until study completion. |
| 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 | up to approximately 2 years | 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. |
| Phase 2: Number of Participants With Any TEAE | up to 420 days | 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. |
Countries
Germany, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: INCB001158 75 mg BID + Daratumumab 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. | 6 |
| Phase 1: INCB001158 100 mg BID + Daratumumab 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. | 4 |
| Phase 2: INCB001158 100 mg BID + Daratumumab 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. | 2 |
| Phase 2: Daratumumab Monotherapy; Cross Over to INCB001158 + Daratumumab 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. | 1 |
| Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab 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. | 2 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Phase 1 | Death | 5 | 2 | 0 | 0 | 0 |
| Phase 2 | Death | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Phase 1: INCB001158 75 mg BID + Daratumumab | Phase 1: INCB001158 100 mg BID + Daratumumab | Phase 2: INCB001158 100 mg BID + Daratumumab | Phase 2: Daratumumab Monotherapy; Cross Over to INCB001158 + Daratumumab | Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 11.7 | 68.0 years STANDARD_DEVIATION 9.83 | 67.0 years STANDARD_DEVIATION 12.73 | NA years | 71.5 years STANDARD_DEVIATION 19.09 | 67.1 years STANDARD_DEVIATION 10.59 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | NA Participants | 1 Participants | NA Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 4 Participants | 2 Participants | NA Participants | 1 Participants | NA Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | NA Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | NA Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | NA Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | NA Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | NA Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | NA Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | NA Participants | 0 Participants | NA Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 2 Participants | NA Participants | 2 Participants | NA Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 1 Participants | NA Participants | 0 Participants | NA Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 1 Participants | NA Participants | 2 Participants | NA Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 6 | 2 / 4 | 0 / 2 | 1 / 1 | 1 / 2 | 9 / 15 |
| other Total, other adverse events | 6 / 6 | 4 / 4 | 1 / 2 | 1 / 1 | 1 / 2 | 13 / 15 |
| serious Total, serious adverse events | 3 / 6 | 1 / 4 | 0 / 2 | 1 / 1 | 0 / 2 | 5 / 15 |
Outcome results
Primary
Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
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.
Time frame: up to 454 days
Population: Full Analysis Population: all participants enrolled in the study who received at least 1 dose of study treatment (INCB001158 or daratumumab subcutaneous \[SC\]). Participants were to be analyzed according to the treatment they were assigned to.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: INCB001158 75 mg BID + Daratumumab | Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 6 Participants |
| Phase 1: INCB001158 100 mg BID + Daratumumab | Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 4 Participants |
Primary
Phase 2: Overall Response Rate (ORR): Number of Participants With a Documented Response of Complete Response (CR), Very Good Partial Response (VGPR), or PR, as Per International Myeloma Working Group (IMWG) Criteria
CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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.
Time frame: up to Day 386
Population: Full Analysis Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: INCB001158 75 mg BID + Daratumumab | Phase 2: Overall Response Rate (ORR): Number of Participants With a Documented Response of Complete Response (CR), Very Good Partial Response (VGPR), or PR, as Per International Myeloma Working Group (IMWG) Criteria | 0 Participants |
| Phase 1: INCB001158 100 mg BID + Daratumumab | Phase 2: Overall Response Rate (ORR): Number of Participants With a Documented Response of Complete Response (CR), Very Good Partial Response (VGPR), or PR, as Per International Myeloma Working Group (IMWG) Criteria | 0 Participants |
| Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab | Phase 2: Overall Response Rate (ORR): Number of Participants With a Documented Response of Complete Response (CR), Very Good Partial Response (VGPR), or PR, as Per International Myeloma Working Group (IMWG) Criteria | 0 Participants |
Secondary
Overall Survival
Overall survival was defined as the time from the first dose of study drug to death from any cause until study completion.
Time frame: up to 923 days (approximately 2.5 years)
Population: Full Analysis Population. As a result of an early-termination decision following a recruitment challenge (no safety-related concerns), a formal analysis was not performed due to an insufficient number of participants enrolled in Phase 2. Overall survival was calculated for individual participants, but data were not formally analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: INCB001158 75 mg BID + Daratumumab | Overall Survival | Maximum value, uncensored | 766 days |
| Phase 1: INCB001158 75 mg BID + Daratumumab | Overall Survival | Minimum value, uncensored | 113 days |
| Phase 1: INCB001158 100 mg BID + Daratumumab | Overall Survival | Minimum value, uncensored | 127 days |
| Phase 1: INCB001158 100 mg BID + Daratumumab | Overall Survival | Maximum value, uncensored | 604 days |
| Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab | Overall Survival | Minimum value, uncensored | NA days |
| Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab | Overall Survival | Maximum value, uncensored | NA days |
| Phase 2: Daratumumab Monotherapy; Cross Over to INCB001158 + Daratumumab | Overall Survival | Maximum value, uncensored | NA days |
| Phase 2: Daratumumab Monotherapy; Cross Over to INCB001158 + Daratumumab | Overall Survival | Minimum value, uncensored | NA days |
| Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab | Overall Survival | Minimum value, uncensored | NA days |
| Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab | Overall Survival | Maximum value, uncensored | NA days |
Secondary
Phase 1: Duration of Response, Defined as Time From First Documented Response of PR or Better (CR, VGPR, PR), as Per IMWG Criteria, Until Date of Disease Progression or Death, Whichever Occurred First
CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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.
Time frame: up to Day 395
Population: No participants had a response of PR or better; thus, analysis was not conducted.
Secondary
Phase 1: Minimal Residual Disease (MRD), Defined as the Percentage of MRD-negative Participants
Bone marrow aspirate was to be collected for MRD analysis.
Time frame: up to approximately 2 years
Population: 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.
Secondary
Phase 1: ORR: Number of Participants With a Documented Response of CR, VGPR, or PR, as Per IMWG Criteria
CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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.
Time frame: up to Day 395
Population: Full Analysis Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: INCB001158 75 mg BID + Daratumumab | Phase 1: ORR: Number of Participants With a Documented Response of CR, VGPR, or PR, as Per IMWG Criteria | 0 Participants |
| Phase 1: INCB001158 100 mg BID + Daratumumab | Phase 1: ORR: Number of Participants With a Documented Response of CR, VGPR, or PR, as Per IMWG Criteria | 0 Participants |
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, VGPR, or PR), as Per IMWG Criteria
CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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.
Time frame: up to Day 395
Population: No participants had a response of PR or better; thus, analysis was not conducted.
Secondary
Phase 2: Duration of Response, Defined as Time From First Documented Response of PR or Better (CR, VGPR, PR), as Per IMWG Criteria, Until Date of Disease Progression or Death, Whichever Occurred First
CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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.
Time frame: up to Day 386
Population: No participants had a response of PR or better; thus, analysis was not conducted.
Secondary
Phase 2: MRD, Defined as the Percentage of MRD-negative Participants
Bone marrow aspirate was to be collected for MRD analysis.
Time frame: up to approximately 2 years
Population: 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.
Secondary
Phase 2: Number of Participants With Any TEAE
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.
Time frame: up to 420 days
Population: Full Analysis Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1: INCB001158 75 mg BID + Daratumumab | Phase 2: Number of Participants With Any TEAE | 1 Participants |
| Phase 1: INCB001158 100 mg BID + Daratumumab | Phase 2: Number of Participants With Any TEAE | 1 Participants |
| Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab | Phase 2: Number of Participants With Any TEAE | 1 Participants |
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, VGPR, or PR), as Per IMWG Criteria
CR: negative immunofixation on serum/urine, disappearance of soft tissue plasmacytomas, \<5% bone marrow plasma cells (PCs). 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.
Time frame: up to Day 386
Population: No participants had a response of PR or better; thus, analysis was not conducted.
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
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.
Time frame: up to approximately 2 years
Population: Full Analysis Population. As a result of an early-termination decision following a recruitment challenge (no safety-related concerns), a formal analysis was not performed due to an insufficient number of participants enrolled in Phase 2. PFS was calculated for individual participants, but data were not formally analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 1: INCB001158 75 mg BID + Daratumumab | 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 | Minimum value, uncensored | 8 days |
| Phase 1: INCB001158 75 mg BID + Daratumumab | 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 | Maximum value, uncensored | 337 days |
| Phase 1: INCB001158 100 mg BID + Daratumumab | 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 | Minimum value, uncensored | 26 days |
| Phase 1: INCB001158 100 mg BID + Daratumumab | 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 | Maximum value, uncensored | 169 days |
| Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab | 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 | Minimum value, uncensored | NA days |
| Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab | 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 | Maximum value, uncensored | NA days |
| Phase 2: Daratumumab Monotherapy; Cross Over to INCB001158 + Daratumumab | 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 | Maximum value, uncensored | NA days |
| Phase 2: Daratumumab Monotherapy; Cross Over to INCB001158 + Daratumumab | 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 | Minimum value, uncensored | NA days |
| Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab | 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 | Minimum value, uncensored | NA days |
| Phase 2: INCB001158 Monotherapy; Cross Over to INCB001158 + Daratumumab | 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 | Maximum value, uncensored | NA days |