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

NCT03837509 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: INCB 01158-2062018-004076-35
• Study Type: interventional
• Target: 15
• Locations: 3 countries
• Sites: 29

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.

Conditions

Relapsed or Refractory Multiple Myeloma

Keywords

Arginase inhibitor; multiple myeloma; Daratumumab

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (10)

• Phase 1: ORR: Number of Participants With a Documented Response of CR, VGPR, or PR, as Per IMWG Criteria

  up to Day 395

• Phase 2: Number of Participants With Any TEAE

  up to 420 days

• 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

• 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

• 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

Study Arms (3)

INCB001158 + daratumumab SC

EXPERIMENTAL

INCB001158 + daratumumab

Drug: INCB001158; Biological: Daratumumab SC

Daratumumab monotherapy and crossover to INC001158+ daratumumab SC

ACTIVE COMPARATOR

Daratumumab will be administered as monotherapy, once confirmed disease progression participants will be crossed over to INCB001158+daratumumad combination therapy.

Biological: Daratumumab SC

INCB001158 monotherapy and crossover to INC001158+ daratumumab SC

EXPERIMENTAL

INCB001158 will be administered as monotherapy, once confirmed disease progression participants will be crossed over to INCB001158+daratumumad combination therapy.

Drug: INCB001158

Interventions

INCB001158 DRUG

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.

INCB001158 + daratumumab SC; INCB001158 monotherapy and crossover to INC001158+ daratumumab SC

Daratumumab SC BIOLOGICAL

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.

Daratumumab monotherapy and crossover to INC001158+ daratumumab SC; INCB001158 + daratumumab SC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (29)

Southern Cancer Center

Daphne, Alabama, 36526, United States

Location

Arizona Oncology Associates (Wilmot)

Tucson, Arizona, 85711, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Comprehensive Cancer Centers of Nevada - Twain

Las Vegas, Nevada, 89169, United States

Location

New York Oncology Hematology

Albany, New York, 12206, United States

Location

Lineberger Comprehensive Cancer Center At University of North Carolina Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Oncology Hematology Care, Inc

Cincinnati, Ohio, 45236, United States

Location

Texas Oncology-Austin Midtown

Austin, Texas, 78705, United States

Location

Texas Oncology - Fort Worth South Henderson

Fort Worth, Texas, 76104, United States

Location

Texas Oncology San Antonio

San Antonio, Texas, 78240, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Virginia Cancer Specialists-Fairfax

Fairfax, Virginia, 22031, United States

Location

Charite - Universit�Tsmedizin Berlin

Berlin, 13353, Germany

Location

University of Heidelberg

Heidelberg, 69117, Germany

Location

Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii

Mainz, 55131, Germany

Location

Universitatsklinikum Munster

Münster, 48149, Germany

Location

Hospital General Universitari Vall D Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic I Provincial

Barcelona, 08036, Spain

Location

Ico Institut Catala D Oncologia

Barcelona, 08908, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

Location

Fundacion Jimenez Diaz University Hospital

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Clinica Universidad de Navarra (Cun)

Pamplona, 31008, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Hospital Universitario Doctor Peset

Valencia, 46017, Spain

Location

Hospital Universitario Y Politcnico de La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

The study was terminated following a recruitment challenge. There were no safety-related concerns.

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

1-855-463-3463

Study Officials

• Sven Gogov, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 7, 2019
• First Posted: February 12, 2019
• Study Start: September 25, 2019
• Primary Completion: April 5, 2022
• Study Completion: April 5, 2022
• Last Updated: November 4, 2025
• Results First Posted: March 20, 2023

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (14); ES (11); DE (4)