Study of INCB053914 in Subjects With Advanced Malignancies

Incyte

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Solid Tumors

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02587598

INCB 53914-101

Details and patient eligibility

About

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).

Enrollment: 97 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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97 participants in 9 patient groups

Parts 1 and 2: INCB053914 100 mg QD

Experimental group

Description:

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

Treatment:

Drug: INCB053914

Parts 3 and 4: INCB053914 + Azacitidine

Experimental group

Description:

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

Treatment:

Drug: INCB053914

Drug: Azacitidine

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

Experimental group

Description:

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.

Treatment:

Drug: I-DAC (Intermediate dose cytarabine)

Drug: INCB053914

Parts 3 and 4: INCB053914 + Ruxolitinib

Experimental group

Description:

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

Treatment:

Drug: INCB053914

Drug: Ruxolitinib

Parts 1 and 2: INCB053914 50 mg

Experimental group

Description:

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

Treatment:

Drug: INCB053914

Parts 1 and 2: INB053914 65 mg

Experimental group

Description:

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

Treatment:

Drug: INCB053914

Parts 1 and 2: INB053914 80 mg

Experimental group

Description:

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

Treatment:

Drug: INCB053914

Parts 1 and 2: INB053914 100 mg BID

Experimental group

Description:

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

Treatment:

Drug: INCB053914

Parts 1 and 2: INB053914 115 mg

Experimental group

Description:

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

Treatment:

Drug: INCB053914