Study of INCB053914 in Subjects With Advanced Malignancies

NCT02587598 | Terminated Phase 1 Results

• 1 other identifier: INCB 53914-101
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 19

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

Outcome Measures

Primary Outcomes (3)

• Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events

  Approximately 7 months

• Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With the Intermediate-dose Cytarabine (I DAC) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) Based on Objective Remission Rate (ORR)

  The primary efficacy endpoint of ORR in patients with AML who received INCB053914 in combination with cytarabine in Part 4 was not assessed because Part 4 was not opened for enrollment owing to this combination regimen not being tolerated in Part 3.

  Approximately 2 months

• Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With Azacitidine in Subjects With Newly Diagnosed AML Who Are 65 Years or Older and Unfit for Intensive Chemotherapy Based on ORR

  The primary efficacy endpoint of ORR in patients with AML who received INCB053914 plus azacitidine in Part 4 was not performed due to limited enrollment as a result of early study termination.

  Approximately 6 months

Secondary Outcomes (21)

• Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)

  1 month

• Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine

  Cycle 1 Day 5

• Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine

  Cycle 1 Day 5

• Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine

  Cycle 1 Day 5

• Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine

  Cycle 1 Day 5

Study Arms (9)

Parts 1 and 2: INCB053914 100 mg QD

EXPERIMENTAL

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

Drug: INCB053914

Parts 3 and 4: INCB053914 + Azacitidine

EXPERIMENTAL

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

Drug: INCB053914; Drug: Azacitidine

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

EXPERIMENTAL

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.

Drug: INCB053914; Drug: I-DAC (Intermediate dose cytarabine)

Parts 3 and 4: INCB053914 + Ruxolitinib

EXPERIMENTAL

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

Drug: INCB053914; Drug: Ruxolitinib

Parts 1 and 2: INCB053914 50 mg

EXPERIMENTAL

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

Drug: INCB053914

Parts 1 and 2: INB053914 65 mg

EXPERIMENTAL

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

Drug: INCB053914

Parts 1 and 2: INB053914 80 mg

EXPERIMENTAL

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

Drug: INCB053914

Parts 1 and 2: INB053914 100 mg BID

EXPERIMENTAL

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

Drug: INCB053914

Parts 1 and 2: INB053914 115 mg

EXPERIMENTAL

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

Drug: INCB053914

Interventions

INCB053914 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; Parts 1 and 2: INB053914 115 mg; Parts 1 and 2: INB053914 65 mg; Parts 1 and 2: INB053914 80 mg; Parts 1 and 2: INCB053914 100 mg QD; Parts 1 and 2: INCB053914 50 mg; Parts 3 and 4: INCB053914 + Azacitidine; Parts 3 and 4: INCB053914 + I-DAC (Intermediate dose cytarabine); Parts 3 and 4: INCB053914 + Ruxolitinib

I-DAC (Intermediate dose cytarabine) DRUG

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

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

Azacitidine DRUG

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

Also known as: Vidaza®

Parts 3 and 4: INCB053914 + Azacitidine

Ruxolitinib DRUG

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

Parts 3 and 4: INCB053914 + Ruxolitinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (19)

The University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

UC Davis comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UCLA Medical Hematology & Oncology

Santa Monica, California, 90095, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Florida Cancer Specialists & Research Institute

Sarasota, Florida, 33916, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Emory University-Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Dana-Farber Cancer Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 69198, United States

Location

Oncology Hematology Care Clinical Trials LLC

Cincinnati, Ohio, 45236, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Texas Oncology

Austin, Texas, 78705, United States

Location

Texas Oncology

Tyler, Texas, 75702, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 37290996 DERIVED

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Primary Myelofibrosis; Lymphoproliferative Disorders; Leukemia, Myeloid, Acute; Lymphoma; Multiple Myeloma

Interventions

Azacitidine; ruxolitinib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Incyte Corporation
• Organization: Call Center

medinfo@incyte.com

1-855-463-3463

Study Officials

• Fred Zheng, M.D.

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 26, 2015
• First Posted: October 27, 2015
• Study Start: December 29, 2015
• Primary Completion: August 11, 2020
• Study Completion: August 11, 2020
• Last Updated: December 8, 2021
• Results First Posted: December 8, 2021

Record last verified: 2021-11

Locations

US (19)