Open-Label Safety and Tolerability Study of INCB057643 in Subjects With Advanced Malignancies

NCT ID: NCT02711137

Last Updated: 2025-10-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 137 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-18
• Study Completion Date: 2019-02-13

Brief Summary

The purpose of the Study is to select a dose and assess the safety and tolerability of INCB057643 as a monotherapy (Part 1 and Part 2) and in combination with standard-of-care (SOC) agents (Part 3 and Part 4) for subjects with advanced malignancies.

Part 1 will determine the maximum tolerated dose of INCB057643 and/or a tolerated dose that demonstrates sufficient pharmacologic activity. Part 2 will further evaluate the safety, preliminary efficacy, PK, and PD of the dose(s) selected in Part 1 in select tumor types including solid tumors, lymphomas and other hematologic malignancies. Part 3 will determine the tolerated dose of INCB057643 in combination with select SOC agents; and assess the safety and tolerability of the combination therapy in select advanced solid tumors and hematologic malignancies. Part 4 will further evaluate the safety, preliminary efficacy, PK, and PD of the selected dose combination from Part 3 in 4 specific advanced solid tumor and hematologic malignancies.

Conditions

Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part1/Treatment Group A : 8mg QD INCB057643

Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA.

Treatment Group A included solid tumors and lymphoma

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Part1/Treatment Group A : 12mg QD INCB057643

Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA.

Treatment Group A included solid tumors and lymphoma

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Part1/Treatment Group A : 16mg QD INCB057643

Initial cohort dose of INCB057643 monotherapy at the protocol specified starting dose in the TGA.

Treatment Group A included solid tumors and lymphoma

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Part1/Treatment Group B : 8mg QD INCB057643

Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Part1/Treatment Group B : 12mg QD INCB057643

Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group B (TGB), based on protocol-specific criteria. Treatment Group B included any acute leukemia, HRMDS, MDS/MPN, or MF.

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Part1/Treatment Group C : 8mg QD INCB057643

Initial cohort dose of INCB054763 monotherapy at the protocol-specified cohort escalation treatment group C (TGC), based on protocol-specific criteria. Treatment Group C includes subjects with MM

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Part2/Treatment Group A : 12 mg INCB057643 Expansion Cohort

Initial cohort dose of INCB054763 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group A (TGA), based on protocol-specific criteria. Part 2 Treatment Group A expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma.

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Part2/Treatment Group B : 12 mg INCB057643 Expansion Cohort

Initial cohort dose of INCB057463 monotherapy at the specified RP2D dose selected in Part 1 cohort escalation treatment group B (TGB), based on protocol-specific criteria. Part 2 Treatment Group B expansion included pancreatic adenocarcinoma, castration-resistant prostrate cancer, breast cancer, high grade serious ovarian cancer, glioblastoma multiform, non-hodgkin's lymphoma, ewing's sarcoma, and solid tumor or lymphoma.

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Part3/Treatment Group A : 8 mg INCB057643 + Gemcitabine 1000mg

Initial cohort dose of INCB057643 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Gemcitabine) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies where Gemcitabine is relevant

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Gemcitabine

Intervention Type: DRUG

Standard of Care (SOC) agents

Part3/Treatment Group B : 8 mg INCB057643 + Paclitaxel 80mg

Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Paclitaxel) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies.

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Paclitaxel

Intervention Type: DRUG

Standard of Care (SOC) agents

Part3/Treatment Group C : 8 mg INCB057643 + Rucaparib 600mg

Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Rucaparib) in relapsed or refractory advanced or metastatic solid tumors and hematologic malignancies.

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Rucaparib

Intervention Type: DRUG

Standard of Care (SOC) agents

Part3/Treatment Group D : 8 mg INCB057643 + Abir +Predni

Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Abiraterone + Prednisone) in Castration Resistant Prostrate Cancer

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Abiraterone

Intervention Type: DRUG

Standard of Care (SOC) agents

Part3/Treatment Group E : 8 mg INCB057643 + Ruxolitinib 20mg

Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Ruxolitinib) in Myelofibrosis.

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Ruxolitinib

Intervention Type: DRUG

Standard of Care (SOC) agents

Part3/Treatment Group F : 8 mg INCB057643 + Azacitidine 75mg

Initial cohort dose of INCB054763 monotherapy based on protocol-specific criteria. Part 3 will determine the MTD and/or a tolerated dose of the combination of INCB057643 and one of the SOC agents (Azacitidine) in Acute Myeloid Leukemia and Myelodysplastic Syndrome

Group Type: EXPERIMENTAL

INCB057643

Intervention Type: DRUG

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Azacitidine

Intervention Type: DRUG

Standard of Care (SOC) agents

Interventions

INCB057643

Initial cohort dose of INCB057643 at the protocol-specified starting dose (Part 1), with subsequent dose escalations based on protocol-specific criteria. The recommended treatment group-specific dose(s) will be taken forward into expansion cohorts (Part 2).

Intervention Type: DRUG

Gemcitabine

Standard of Care (SOC) agents

Intervention Type: DRUG

Paclitaxel

Standard of Care (SOC) agents

Intervention Type: DRUG

Rucaparib

Standard of Care (SOC) agents

Intervention Type: DRUG

Abiraterone

Standard of Care (SOC) agents

Intervention Type: DRUG

Ruxolitinib

Standard of Care (SOC) agents

Intervention Type: DRUG

Azacitidine

Standard of Care (SOC) agents

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed diagnosis of relapsed or refractory advanced or metastatic malignancies:

• Part 1: solid tumors or lymphomas, or hematologic malignancies
• Part 2: histologically confirmed disease in specific tumor types
• Part 3: advanced solid tumor or hematologic malignancy
• Part 4: select advanced solid tumor or hematologic malignancy
• For Part 1 and 2, subjects must have progressed following at least 1 line of prior therapy and there is no further established therapy that is known to provide clinical benefit (including subjects who are intolerant to the established therapy)
• For Parts 3 and 4, subjects must have progressed following at least 1 line of prior therapy, and the treatment with the select SOC agent is relevant for the specific disease cohort.
• Life expectancy > 12 weeks, for MF subjects in Parts 3 and 4, life expectancy > 24 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status

• Parts 1 and 3: 0 or 1
• Parts 2 and 4: 0, 1, or 2
• Willingness to avoid pregnancy or fathering children

Exclusion Criteria

• Inadequate bone marrow function per protocol-specified hemoglobin, platelet count, and absolute neutrophil count
• Inadequate organ function per protocol-specified total bilirubin, AST and ALT, creatinine clearance and alkaline phosphatase.
• Receipt of anticancer medications or investigational drugs within protocol-specified intervals
• Unless approved by the medical monitor, may not have received an allogeneic hematopoietic stem cell transplant within 6 months before treatment, or have active graft-versus-host-disease following allogeneic transplant
• Unless approved by the medical monitor, may not have received autologous hematopoietic stem cell transplant within 3 months before treatment
• Any unresolved toxicity ≥ Grade 2 (except stable Grade 2 peripheral neuropathy or alopecia) from previous anticancer therapy
• Radiotherapy within the 2 weeks before initiation of treatment. Palliative radiation treatment to nonindex or bone lesions performed less than 2 weeks before treatment initiation may be considered with medical monitor approval
• Currently active and uncontrolled infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment
• Untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed
• History or presence of abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful
• Type 1 diabetes or uncontrolled Type 2 diabetes
• HbA1c of ≥ 8% (all subjects will have HbA1c test at screening)
• Any sign of clinically significant bleeding
• Coagulation panel within protocol-specified parameters

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fred Zheng, MD, PhD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

University of Alabama

Birmingham, Alabama, United States

University of California

La Jolla, California, United States

Sarah Cannon Research Institute at Health One

Denver, Colorado, United States

Yale University

New Haven, Connecticut, United States

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Hematology - Oncology Associates of Treasure Coast

Port Saint Lucie, Florida, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Washington University

St Louis, Missouri, United States

University of Rochester, Wilmot Cancer Center

Rochester, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Oncology Consultants, P.A.

Houston, Texas, United States

The Methodist Hospital

Houston, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

MultiCare Institute for Research and Innovation

Tacoma, Washington, United States

Institut Jules Bordet, Clinical Trial Conduct Unit

Brussels, , Belgium

HÔPITAL SAINT-LOUIS, Service Hématologie Adultes

Paris, , France

Countries

United States; Belgium; France

References

Falchook G, Rosen S, LoRusso P, Watts J, Gupta S, Coombs CC, Talpaz M, Kurzrock R, Mita M, Cassaday R, Harb W, Peguero J, Smith DC, Piha-Paul SA, Szmulewitz R, Noel MS, Yeleswaram S, Liu P, Switzky J, Zhou G, Zheng F, Mehta A. Development of 2 Bromodomain and Extraterminal Inhibitors With Distinct Pharmacokinetic and Pharmacodynamic Profiles for the Treatment of Advanced Malignancies. Clin Cancer Res. 2020 Mar 15;26(6):1247-1257. doi: 10.1158/1078-0432.CCR-18-4071. Epub 2019 Sep 16.

Reference Type: DERIVED

PMID: 31527168 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2017-002641-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCB 57643-101

Identifier Type: -

Identifier Source: org_study_id