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

Relapsed or Refractory Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03837509
• Other study ID #: INCB 01158-206
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: September 25, 2019
• Est. completion date: April 5, 2022

Study information

• Verified date: February 2023
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: April 5, 2022
• Est. primary completion date: April 5, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed or Refractory Multiple Myeloma

Intervention

Drug:
• INCB001158
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.

Biological:
• Daratumumab 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	up to 454 days
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.	up to Day 386
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.	up to Day 395
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.	up to 420 days
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.	up to Day 395
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.	up to Day 386
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.	up to Day 395
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.	up to Day 386
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.	up to approximately 2 years
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.	up to approximately 2 years
Secondary	Phase 2: MRD, Defined as the Percentage of MRD-negative Participants	Bone marrow aspirate was to be collected for MRD analysis.	up to approximately 2 years
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.	up to 923 days (approximately 2.5 years)