Clinical trial NCT03837509: INCB001158 Combined With Subcutaneous (SC) Daratumumab, Compared to Daratumumab SC, in Relapsed or Refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: Arginase inhibitor
multiple myeloma
Daratumumab
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2019-02-12
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
timeFrame: up to 454 days
measure: 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
timeFrame: up to Day 386
Secondary outcomes:
measure: Phase 1: ORR: Number of Participants With a Documented Response of CR, VGPR, or PR, as Per IMWG Criteria
timeFrame: up to Day 395
measure: Phase 2: Number of Participants With Any TEAE
timeFrame: up to 420 days
measure: 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
timeFrame: up to Day 395
measure: 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
timeFrame: up to Day 386
measure: 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
timeFrame: up to Day 395
measure: 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
timeFrame: up to Day 386
measure: 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
timeFrame: up to approximately 2 years
measure: Phase 1: Minimal Residual Disease (MRD), Defined as the Percentage of MRD-negative Participants
timeFrame: up to approximately 2 years
measure: Phase 2: MRD, Defined as the Percentage of MRD-negative Participants
timeFrame: up to approximately 2 years
measure: Overall Survival
timeFrame: up to 923 days (approximately 2.5 years)
Other outcomes:
Locations:
city: Daphne
country: United States
facility: Southern Cancer Center
state: Alabama
city: Tucson
country: United States
facility: Arizona Oncology Associates (Wilmot)
state: Arizona
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Twain
state: Nevada
city: Albany
country: United States
facility: New York Oncology Hematology
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center At University of North Carolina Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care, Inc
state: Ohio
city: Austin
country: United States
facility: Texas Oncology-Austin Midtown
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth South Henderson
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology San Antonio
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists-Fairfax
state: Virginia
city: Berlin
country: Germany
facility: Charite - Universit�Tsmedizin Berlin
city: Heidelberg
country: Germany
facility: University of Heidelberg
city: Mainz
country: Germany
facility: Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii
city: Munster
country: Germany
facility: Universitatsklinikum Munster
city: Barcelona
country: Spain
facility: Hospital General Universitari Vall D Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Barcelona
country: Spain
facility: Ico Institut Catala D Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz University Hospital
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra (Cun)
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
city: Valencia
country: Spain
facility: Hospital Universitario Y Politcnico de La Fe
Study officials:
affiliation: Incyte Corporation
name: Sven Gogov, MD
role: STUDY_DIRECTOR
References: