Study of INCB053914 in Subjects With Advanced Malignancies

Solid Tumors Clinical Trial

Official title:

A Phase 1/2 Study of INCB053914 in Subjects With Advanced Malignancies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02587598
• Other study ID #: INCB 53914-101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: December 29, 2015
• Est. completion date: August 11, 2020

Study information

• Verified date: November 2021
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 97
• Est. completion date: August 11, 2020
• Est. primary completion date: August 11, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• 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.
• I-DAC (Intermediate dose cytarabine)
Cytarabine dose will be 1 g/m^2. Cytarabine will be administered as an intravenous (IV) infusion.
• Azacitidine
Azacitidine dose will be 75 mg/m^2. Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
• Ruxolitinib
Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Emory University-Winship Cancer Institute	Atlanta	Georgia
United States	Texas Oncology	Austin	Texas
United States	University of Maryland	Baltimore	Maryland
United States	Dana-Farber Cancer Center	Boston	Massachusetts
United States	Oncology Hematology Care Clinical Trials LLC	Cincinnati	Ohio
United States	Mayo Clinic Florida	Jacksonville	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Tennessee Oncology	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	UC Davis comprehensive Cancer Center	Sacramento	California
United States	UCLA Medical Hematology & Oncology	Santa Monica	California
United States	Florida Cancer Specialists & Research Institute	Sarasota	Florida
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	The University of Arizona Cancer Center	Tucson	Arizona
United States	Texas Oncology	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events		Approximately 7 months
Primary	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
Primary	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	Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)	Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay	1 month
Secondary	Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine		Cycle 1 Day 5
Secondary	Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine		Cycle 1 Day 5
Secondary	Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine		Cycle 1 Day 5
Secondary	Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine		Cycle 1 Day 5
Secondary	Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine		Cycle 1 Day 5
Secondary	Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine		Cycle 1 Day 8
Secondary	Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine		Cycle 1 Day 8
Secondary	Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine		Cycle 1 Day 8
Secondary	Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine		Cycle 1 Day 8
Secondary	Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine		Cycle 1 Day 8
Secondary	Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib		Regimen 2 Week 4
Secondary	Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib		Regimen 2 Week 4
Secondary	Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib		Regimen 2 Week 4
Secondary	Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib		Regimen 2 Week 4
Secondary	Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib		Regimen 2 Week 4
Secondary	Pharmacokinetics: Tmax of INCB053914 Monotherapy		Cycle 1 Day 8
Secondary	Pharmacokinetics: AUCtau of INCB053914 Monotherapy		Cycle 1 Day 8
Secondary	Pharmacokinetics: CL/F of INCB053914 Monotherapy		Cycle 1 Day 8
Secondary	Pharmacokinetics: Cmax of INCB053914 Monotherapy		Cycle 1 Day 8
Secondary	Pharmacokinetics: Ctau of INCB053914 Monotherapy		Cycle 1 Day 8