Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms

Sponsor

Incyte Corporation (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04279847

Collaborator

(none)

Enrollment

Locations

Arms

44.6

Anticipated Duration (Months)

1.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of INCB057643 as monotherapy or combination with ruxolitinib for participants with myelofibrosis and other myeloid neoplasms.

Condition or Disease	Intervention/Treatment	Phase
Myelofibrosis Myelodysplastic Syndrome Myelodysplastic/Myeloproliferative Neoplasm Overlap Syndrome Myeloproliferative Neoplasm Relapsed or Refractory Primary Myelofibrosis Secondary Myelofibrosis (Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis)	Drug: INCB057643 Drug: Ruxolitinib	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

39 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

monotherapy and ruxoltinib combinationmonotherapy and ruxoltinib combination

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Open-Label, Safety and Tolerability Study of INCB057643 in Participants With Myelofibrosis and Other Advanced Myeloid Neoplasms

Actual Study Start Date :

Feb 23, 2021

Anticipated Primary Completion Date :

Nov 11, 2024

Anticipated Study Completion Date :

Nov 11, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: INCB057643 Monotherapy INCB057643 dose escalation (Part 1) and dose expansion (Part 2: treatment group A).	Drug: INCB057643 INCB057643 dose escalation (Part 1) and dose expansion (Part 2).
Experimental: INCB057643 Combination with Ruxolitinib Combination arm in dose escalation (Part 1) and dose expansion (Part 2: Treatment Group B)	Drug: INCB057643 INCB057643 dose escalation (Part 1) and dose expansion (Part 2). Drug: Ruxolitinib Ruxolitinib will be administered twice a day using the dose designated as the stable dose at the time of the screening visit for each subject. Acceptable doses are 5 mg BID to 25 mg BID.

Arm

Intervention/Treatment

Experimental: INCB057643 Monotherapy

INCB057643 dose escalation (Part 1) and dose expansion (Part 2: treatment group A).

Drug: INCB057643

INCB057643 dose escalation (Part 1) and dose expansion (Part 2).

Experimental: INCB057643 Combination with Ruxolitinib

Combination arm in dose escalation (Part 1) and dose expansion (Part 2: Treatment Group B)

Drug: INCB057643

INCB057643 dose escalation (Part 1) and dose expansion (Part 2).

Drug: Ruxolitinib

Ruxolitinib will be administered twice a day using the dose designated as the stable dose at the time of the screening visit for each subject. Acceptable doses are 5 mg BID to 25 mg BID.

Outcome Measures

Primary Outcome Measures

Number of treatment-emergent adverse events [Up to approximately 9 months]
Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug monotherapy and in combination with ruxolitinib.

Secondary Outcome Measures

Overall Response Rate [up to approximately 9 months]
Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.
Symptom Response Rate [Week 24]
Defined as the proportion of participants who achieve a protocol defined reduction in Total Symptomatic Score (TSS) relative to baseline as measured by the MPN-SAF TSS
Anemia response [Up to approximately 9 months]
Hemoglobin increase of 1.5 g/dL relative to baseline for any "rolling" 12-week period during the first 24 weeks of treatment, if Transfusion Independent (TI) at baseline or achieving TI for any rolling 12 week period during the first 24 weeks of treatment if Transfusion Dependent (TD) at baseline
Duration of Anemia Response [Up to approximately 9 months]
The interval from the first onset of anemia response to the earliest date of loss of anemia response that persists for at least 4 weeks or death from any cause for the TI participants at baseline or duration of RBC-TI period for participants achieving RBC-TI for at least 12 consecutive weeks during the first 24 weeks of treatment for the TD participants at baseline, or Mean change from baseline in the hemoglobin value over 12-week treatment periods
Rate of red blood cell (RBC) transfusion dependency [24 and 48 Weeks]
Defined as the average number of RBC units per participant month
Percentage change in Spleen Volume [12 and 24 weeks]
Defined as percentage of participants with a protocol defined Spleen Volume Reduction (SVR)
Spleen length response [Up to approximately 9 months]
Defined as the proportion of participants achieving a protocol defined reduction in spleen length at any visit relative to baseline as measured by palpation

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Relapsed or refractory primary myelofibrosis (MF), secondary MFs (post-polycythemia vera MF, post- essential thrombocythemia MF) myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), and myelodysplastic/myeloproliferative neoplasm overlap syndrome (MDS/MPN)
Must not be a candidate for potentially curative therapy, including hematopoietic stem-cell transplantation.
Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate at screening/baseline, or archival sample obtained since completion of most recent therapy.
Willingness to avoid pregnancy or fathering children.

Exclusion Criteria:

Prior receipt of a BET inhibitor within 5 half-lives of the compound, and/or experienced BET inhibitor-related AE(s) resulting in dose discontinuation.
Receipt of anticancer medications or investigational drugs within the protocol-defined interval before the first dose of study treatment:

Note: For participants in Part 2, Treatment Group B, ruxolitinib will continue at the participants' current, ongoing doses. No ruxolitinib washout is needed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama At Birmingham	Birmingham	Alabama	United States	35294
2	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
3	University of Miami Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
4	Emory University - Winship Cancer Institute	Atlanta	Georgia	United States	30322
5	Rutgers Cancer Institute of Nj	New Brunswick	New Jersey	United States	08901
6	Weill Medical College of Cornell University	New York	New York	United States	10021
7	University of North Carolina At Chapel Hill	Chapel Hill	North Carolina	United States	27514
8	University of Cincinnati Cancer Institute	Cincinnati	Ohio	United States	45267
9	Md Anderson Cancer Center	Houston	Texas	United States	77030
10	Huntsman Cancer Institute At University of Utah	Salt Lake City	Utah	United States	84112
11	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
12	Princess Margaret Cancer Center	Toronto	Ontario	Canada	MG5 2M9
13	Helsinki University Central Hospital	Helsinki		Finland	00029
14	L AZIENDA OSPEDALIERO-UNIVERSITARIA DI BOLOGNA POLICLINICO S. ORSOLA ï¿½ MALPIGHI	Bologna		Italy	40138
15	Azienda Ospedaliero-Universitaria Careggi (Aouc)	Firenze		Italy	50134
16	Fondazione Irccs Ca Granda Ospedale Maggiore	Milan		Italy	20122
17	Azienda Policlinico Umberto 1 Universita Sapienza Di Roma	Rome		Italy	00161
18	Fujita Health University Hospital	Aichi		Japan	470-1192
19	Chiba University Hospital	Chiba		Japan	260-8677
20	National Cancer Center Hospital East	Chiba		Japan	277-8577
21	Kyushu University Hospital	Fukuoka		Japan
22	Ico Hospital Germans Trias I Pujol	Badalona		Spain	08916
23	Hospital Universitario Insular de Gran Canaria	Las Palmas		Spain	35019
24	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
25	Hospital Universitario Virgen de La Arrixaca	Murcia		Spain	30120
26	Hospital Clinico Universitario de Salamanca	Salamanca		Spain	37007
27	The Christie Nhs Foundation Trust Uk	Manchester		United Kingdom	M20 4BV
28	University of Oxford	Oxford		United Kingdom	OX3 9DS