Clinical trial NCT02587598: Study of INCB053914 in Subjects With Advanced Malignancies
Official title: A Phase 1/2 Study of INCB053914 in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
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
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2015-10-27
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
timeFrame: Approximately 7 months
measure: 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)
timeFrame: Approximately 2 months
measure: 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
timeFrame: Approximately 6 months
Secondary outcomes:
measure: Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
timeFrame: 1 month
measure: Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
timeFrame: Cycle 1 Day 5
measure: Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
timeFrame: Cycle 1 Day 5
measure: Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
timeFrame: Cycle 1 Day 5
measure: Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
timeFrame: Cycle 1 Day 5
measure: Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
timeFrame: Cycle 1 Day 5
measure: Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
timeFrame: Cycle 1 Day 8
measure: Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
timeFrame: Cycle 1 Day 8
measure: Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
timeFrame: Cycle 1 Day 8
measure: Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
timeFrame: Cycle 1 Day 8
measure: Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
timeFrame: Cycle 1 Day 8
measure: Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
timeFrame: Regimen 2 Week 4
measure: Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
timeFrame: Regimen 2 Week 4
measure: Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
timeFrame: Regimen 2 Week 4
measure: Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
timeFrame: Regimen 2 Week 4
measure: Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
timeFrame: Regimen 2 Week 4
measure: Pharmacokinetics: Tmax of INCB053914 Monotherapy
timeFrame: Cycle 1 Day 8
measure: Pharmacokinetics: AUCtau of INCB053914 Monotherapy
timeFrame: Cycle 1 Day 8
measure: Pharmacokinetics: CL/F of INCB053914 Monotherapy
timeFrame: Cycle 1 Day 8
measure: Pharmacokinetics: Cmax of INCB053914 Monotherapy
timeFrame: Cycle 1 Day 8
measure: Pharmacokinetics: Ctau of INCB053914 Monotherapy
timeFrame: Cycle 1 Day 8
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Sacramento
country: United States
facility: UC Davis comprehensive Cancer Center
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Hematology & Oncology
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists & Research Institute
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University-Winship Cancer Institute
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Cincinnati
country: United States
facility: Oncology Hematology Care Clinical Trials LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: Tyler
country: United States
facility: Texas Oncology
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Incyte Corporation
name: Fred Zheng, M.D.
role: STUDY_DIRECTOR
References: