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

Sponsor

Incyte Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT03837509

Collaborator

(none)

Enrollment

Locations

Arms

30.3

Actual Duration (Months)

0.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed or Refractory Multiple Myeloma	Drug: INCB001158 Biological: Daratumumab SC	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 25, 2019

Actual Primary Completion Date :

Apr 5, 2022

Actual Study Completion Date :

Apr 5, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INCB001158 + daratumumab SC INCB001158 + daratumumab	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.
Active Comparator: Daratumumab monotherapy and crossover to INC001158+ daratumumab SC Daratumumab will be administered as monotherapy, once confirmed disease progression participants will be crossed over to INCB001158+daratumumad combination therapy.	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.
Experimental: INCB001158 monotherapy and crossover to INC001158+ daratumumab SC INCB001158 will be administered as monotherapy, once confirmed disease progression participants will be crossed over to INCB001158+daratumumad combination therapy.	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.

Arm

Intervention/Treatment

Experimental: INCB001158 + daratumumab SC

INCB001158 + daratumumab

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.

Active Comparator: Daratumumab monotherapy and crossover to INC001158+ daratumumab SC

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

Biological: Daratumumab SC

Experimental: INCB001158 monotherapy and crossover to INC001158+ daratumumab SC

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

Drug: INCB001158

Outcome Measures

Primary Outcome Measures

Phase 1: Number of treatment-emergent adverse events with INCB001158 in combination with daratumumab [Up to approximately 2 years]
Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Phase 2: Objective response rate with INCB001158 in combination with daratumumab compared to daratumumab monotherapy [Up to approximately 2 years]
Defined as the proportion of participants with a documented response of partial response (PR) or better, per International Myeloma Working Group (IMWG) criteria.

Secondary Outcome Measures

Time to response [Up to approximately 2 years]
Defined as the time from the first dose of study drug to the first documented response PR or better, as per IMWG criteria.
Duration of response [Up to approximately 2 years]
Defined as time from first documented response PR or better, as per IMWG criteria, until date of disease progression or death, whichever occurs first.
Progression-free survival [Up to approximately 3 years]
Defined as the duration from the date of first dose of study drug until either progressive disease (PD), as per IMWG criteria, or death, whichever occurs first.
Minimal residual disease [Up to approximately 2 years]
Defined as the percentage of MRD-negative participants.
Overall survival [Up to approximately 3 years]
Defined as the time from the first dose of study drug to the first documented response PR or better, as per IMWG criteria.
Phase 2: Number of treatment-emergent adverse events with INCB001158 as monotherapy at RP2D [Up to approximately 2 years]
Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug
Phase 2: Compare Number of treatment-emergent adverse events of INCB001158 in combination with daratumumab SC to daratumumab SC monotherapy. [Up to approximately 2 years]
Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug
Phase 1: Objective response rate with INCB001158 in combination with daratumumab [Up to approximately 2 years]
Defined as the proportion of participants with a documented response of partial response (PR) or better, per International Myeloma Working Group (IMWG) criteria

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern Cancer Center	Daphne	Alabama	United States	36526
2	Arizona Oncology Associates (Wilmot)	Tucson	Arizona	United States	85711
3	Rocky Mountain Cancer Centers	Denver	Colorado	United States	80218
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	Comprehensive Cancer Centers of Nevada - Twain	Las Vegas	Nevada	United States	89169
6	New York Oncology Hematology	Albany	New York	United States	12206
7	Lineberger Comprehensive Cancer Center At University of North Carolina Chapel Hill	Chapel Hill	North Carolina	United States	27514
8	Oncology Hematology Care, Inc	Cincinnati	Ohio	United States	45236
9	Texas Oncology-Austin Midtown	Austin	Texas	United States	78705
10	Texas Oncology - Fort Worth South Henderson	Fort Worth	Texas	United States	76104
11	Texas Oncology San Antonio	San Antonio	Texas	United States	78240
12	Texas Oncology - Tyler	Tyler	Texas	United States	75702
13	University of Virginia	Charlottesville	Virginia	United States	22903
14	Virginia Cancer Specialists-Fairfax	Fairfax	Virginia	United States	22031
15	Charite - Universit�Tsmedizin Berlin	Berlin		Germany	13353
16	University of Heidelberg	Heidelberg		Germany	69117
17	Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii	Mainz		Germany	55131
18	Universitatsklinikum Munster	Munster		Germany	48149
19	Hospital General Universitari Vall D Hebron	Barcelona		Spain	08035
20	Hospital Clinic I Provincial	Barcelona		Spain	08036
21	Ico Institut Catala D Oncologia	Barcelona		Spain	08908
22	Hospital Universitario Ramon Y Cajal	Madrid		Spain	28034
23	Fundacion Jimenez Diaz University Hospital	Madrid		Spain	28040
24	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
25	Clinica Universidad de Navarra (Cun)	Pamplona		Spain	31008
26	Hospital Clinico Universitario de Salamanca	Salamanca		Spain	37007
27	Hospital Universitario Marques de Valdecilla	Santander		Spain	39008
28	Hospital Universitario Doctor Peset	Valencia		Spain	46017
29	Hospital Universitario Y Politcnico de La Fe	Valencia		Spain	46026