INCB001158 Combined With Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, in Relapsed or Refractory Multiple Myeloma

Phase 1

Terminated

Conditions: Relapsed or Refractory Multiple Myeloma

Interventions: Drug: INCB001158
Biological: Daratumumab SC

Registration Number: NCT03837509

Lead Sponsor: Incyte Corporation

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 15

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
INCB001158 monotherapy and crossover to INC001158+ daratumumab SC	INCB001158	INCB001158 will be administered as monotherapy, once confirmed disease progression participants will be crossed over to INCB001158+daratumumad combination therapy.
Daratumumab monotherapy and crossover to INC001158+ daratumumab SC	Daratumumab SC	Daratumumab will be administered as monotherapy, once confirmed disease progression participants will be crossed over to INCB001158+daratumumad combination therapy.
INCB001158 + daratumumab SC	Daratumumab SC	INCB001158 + daratumumab
INCB001158 + daratumumab SC	INCB001158	INCB001158 + daratumumab

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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 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: 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 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.

Trial Locations

Locations (29): New York Oncology Hematology
🇺🇸
Albany, New York, United States
Virginia Cancer Specialists-Fairfax
🇺🇸
Fairfax, Virginia, United States
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
University of Heidelberg
🇩🇪
Heidelberg, Germany
Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
🇩🇪
Mainz, Germany
Universitatsklinikum Munster
🇩🇪
Munster, Germany
Rocky Mountain Cancer Centers
🇺🇸
Denver, Colorado, United States
Comprehensive Cancer Centers of Nevada - Twain
🇺🇸
Las Vegas, Nevada, United States
Texas Oncology San Antonio
🇺🇸
San Antonio, Texas, United States
Arizona Oncology Associates (Wilmot)
🇺🇸
Tucson, Arizona, United States
Southern Cancer Center
🇺🇸
Daphne, Alabama, United States
Oncology Hematology Care, Inc
🇺🇸
Cincinnati, Ohio, United States
Texas Oncology - Tyler
🇺🇸
Tyler, Texas, United States
Charite - Universit�Tsmedizin Berlin
🇩🇪
Berlin, Germany
University of Virginia
🇺🇸
Charlottesville, Virginia, United States
Hospital General Universitari Vall D Hebron
🇪🇸
Barcelona, Spain
Hospital Clinic I Provincial
🇪🇸
Barcelona, Spain
Ico Institut Catala D Oncologia
🇪🇸
Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Fundacion Jimenez Diaz University Hospital
🇪🇸
Madrid, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸
Madrid, Spain
Hospital Clinico Universitario de Salamanca
🇪🇸
Salamanca, Spain
Clinica Universidad de Navarra (Cun)
🇪🇸
Pamplona, Spain
Hospital Universitario Doctor Peset
🇪🇸
Valencia, Spain
Hospital Universitario Y Politcnico de La Fe
🇪🇸
Valencia, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸
Santander, Spain
Texas Oncology - Fort Worth South Henderson
🇺🇸
Fort Worth, Texas, United States
Lineberger Comprehensive Cancer Center At University of North Carolina Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Texas Oncology-Austin Midtown
🇺🇸
Austin, Texas, United States