Study of INCB053914 in Subjects With Advanced Malignancies

NCT ID: NCT02587598

Last Updated: 2021-12-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-29
• Study Completion Date: 2020-08-11

Brief Summary

This is an open-label, dose-escalation study of the proviral integration site of Moloney murine leukemia virus (PIM) kinase inhibitor INCB053914 in subjects with advanced malignancies. The study will be conducted in 4 parts. Part 1 (monotherapy dose escalation) will evaluate safety and determine the maximum tolerated dose of INCB053914 monotherapy and the recommended phase 2 dose(s) (a tolerated pharmacologically active dose that will be taken forward into the remaining parts of the study). Part 2 (monotherapy dose expansion) will further evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the recommended Phase 2 dose(s). Part 3 (combination dose finding) will evaluate safety of INCB053914 in combination with select standard of care (SOC) agents and will identify the optimal INCB053914 dose in combination with conventional SOC regimens to take forward into Part 4. Part 4 (combination dose expansion) will further evaluate the safety, efficacy and pharmacokinetics of the recommended Phase 2 dose combination(s).

Conditions

Solid Tumors

Keywords

leukemia; myelodysplastic syndrome (MDS); myelodysplastic/myeloproliferative neoplasms (MDS/MPN); myelofibrosis (MF); lymphoproliferative disorders; acute myeloid leukemia (AML); lymphomas; multiple myeloma (MM); PIM kinases

Study Design

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

Study Groups

Parts 1 and 2: INCB053914 100 mg QD

INCB053914 will be self-administered orally once a day in as a 100mg immediate release tablet as a monotherapy.

Group Type: EXPERIMENTAL

INCB053914

Intervention Type: DRUG

Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria.

INCB053914 tablets to be administered by mouth.

Parts 3 and 4: INCB053914 + Azacitidine

Azacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914.

Group Type: EXPERIMENTAL

INCB053914

Intervention Type: DRUG

Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria.

INCB053914 tablets to be administered by mouth.

Azacitidine

Intervention Type: DRUG

Azacitidine dose will be 75 mg/m\^2. Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).

Parts 3 and 4: INCB053914 + I-DAC (Intermediate dose cytarabine)

I-DAC (intermediate dose cytarabine) will be administered at a dose of 1 g/m2 per day as an infusion as a combination therapy with INCB053914.

Group Type: EXPERIMENTAL

INCB053914

Intervention Type: DRUG

Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria.

INCB053914 tablets to be administered by mouth.

I-DAC (Intermediate dose cytarabine)

Intervention Type: DRUG

Cytarabine dose will be 1 g/m\^2. Cytarabine will be administered as an intravenous (IV) infusion.

Parts 3 and 4: INCB053914 + Ruxolitinib

Ruxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.

Group Type: EXPERIMENTAL

INCB053914

Intervention Type: DRUG

Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria.

INCB053914 tablets to be administered by mouth.

Ruxolitinib

Intervention Type: DRUG

Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.

Parts 1 and 2: INCB053914 50 mg

INCB053914 will be self-administered orally twice day in as a 50mg immediate release tablet as a monotherapy.

Group Type: EXPERIMENTAL

INCB053914

Intervention Type: DRUG

Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria.

INCB053914 tablets to be administered by mouth.

Parts 1 and 2: INB053914 65 mg

INCB053914 will be self-administered orally twice day in as a 65mg immediate release tablet as a monotherapy.

Group Type: EXPERIMENTAL

INCB053914

Intervention Type: DRUG

Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria.

INCB053914 tablets to be administered by mouth.

Parts 1 and 2: INB053914 80 mg

INCB053914 will be self-administered orally twice day in as a 80mg immediate release tablet as a monotherapy.

Group Type: EXPERIMENTAL

INCB053914

Intervention Type: DRUG

Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria.

INCB053914 tablets to be administered by mouth.

Parts 1 and 2: INB053914 100 mg BID

INCB053914 will be self-administered orally twice day in as a 100mg immediate release tablet as a monotherapy.

Group Type: EXPERIMENTAL

INCB053914

Intervention Type: DRUG

Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria.

INCB053914 tablets to be administered by mouth.

Parts 1 and 2: INB053914 115 mg

INCB053914 will be self-administered orally twice day in as a 115mg immediate release tablet as a monotherapy.

Group Type: EXPERIMENTAL

INCB053914

Intervention Type: DRUG

Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria.

INCB053914 tablets to be administered by mouth.

Interventions

INCB053914

Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria.

INCB053914 tablets to be administered by mouth.

Intervention Type: DRUG

I-DAC (Intermediate dose cytarabine)

Cytarabine dose will be 1 g/m\^2. Cytarabine will be administered as an intravenous (IV) infusion.

Intervention Type: DRUG

Azacitidine

Azacitidine dose will be 75 mg/m\^2. Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).

Intervention Type: DRUG

Ruxolitinib

Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.

Intervention Type: DRUG

Other Intervention Names

Vidaza®

Eligibility Criteria

Inclusion Criteria

• Aged 18 years or older
• Confirmed diagnosis of select advanced malignancy
• Parts 1 and 2:

• Unresponsive to currently available therapy and there is no standard-of-care therapy available in the judgment of the investigator.
• Not currently a candidate for curative treatment
• Parts 3 and 4:

• Subjects with relapsed/refractory AML must have received either induction chemotherapy for AML or hypomethylating agents for hematologic disease before AML.
• Elderly subjects (≥ 65 years) with newly diagnosed AML must be treatment naive and unfit for intensive chemotherapy.
• Myelofibrosis subjects must have been treated with ruxolitinib for ≥ 6 months with a stable dose for ≥ 8 weeks (acceptable doses are 5 mg twice daily [BID] to 25 mg BID).
• Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate, or archival sample obtained since completion of most recent therapy (as appropriate to subjects with existing bone marrow disease or for whom bone marrow examination is a component of disease status assessment)
• Eastern Cooperative Oncology Group (ECOG) performance status

• Part 1: 0 or 1
• Parts 2, 3 and 4: 0, 1, or 2
• Life expectancy > 12 weeks or ≥ 24 weeks for Part 3 and Part 4 MF subjects.

Exclusion Criteria

• Inadequate bone marrow or organ function
• Received an investigational agent within 5 half-lives or 14 days, whichever is longer, prior to receiving the first dose of study drug
• Received non-biologic anticancer medication within 5 half-lives prior to receiving the first dose of study drug (within 6 weeks for mitomycin-C or nitrosoureas), within 28 days for any antibodies or biological therapies
• Prior receipt of a PIM inhibitor
• Any history of disease involving the central nervous system (Part 1). Known active disease involving the central nervous system (Part 2).
• Screening corrected QT interval (QTc) interval > 470 milliseconds
• Radiotherapy within the 2 weeks prior to initiation of treatment
• Chronic or current active infection requiring systemic antibiotic, antifungal, or antiviral treatment

• 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, M.D.

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

The University of Arizona Cancer Center

Tucson, Arizona, United States

UC Davis comprehensive Cancer Center

Sacramento, California, United States

UCLA Medical Hematology & Oncology

Santa Monica, California, United States

Yale University

New Haven, Connecticut, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

Florida Cancer Specialists & Research Institute

Sarasota, Florida, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Emory University-Winship Cancer Institute

Atlanta, Georgia, United States

University of Maryland

Baltimore, Maryland, United States

Dana-Farber Cancer Center

Boston, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Oncology Hematology Care Clinical Trials LLC

Cincinnati, Ohio, United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Tennessee Oncology

Nashville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Texas Oncology

Austin, Texas, United States

Texas Oncology

Tyler, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

Patel MR, Donnellan W, Byrne M, Asch AS, Zeidan AM, Baer MR, Fathi AT, Kuykendall AT, Zheng F, Walker C, Cheng L, Marando C, Savona MR. Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies. Clin Lymphoma Myeloma Leuk. 2023 Sep;23(9):674-686. doi: 10.1016/j.clml.2023.05.002. Epub 2023 May 15.

Reference Type: DERIVED

PMID: 37290996 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

INCB 53914-101

Identifier Type: -

Identifier Source: org_study_id