Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

INCB053914 in combination with INCB050465.

Dose Escalation: INCB053914 at the protocol-defined starting dose in combination with INCB050465, with dose modifications based on tolerability criteria.

Dose Expansion: Recommended dose from the dose-escalation study.

INCB053914

Dose Escalation: INCB050465 at the protocol-defined starting dose in combination with INCB053914, with dose modifications based on tolerability criteria.

Dose Expansion: Recommended dose from the dose-escalation study.

INCB050465

Fred Zheng, MD

The purpose of this study is to evaluate the safety and tolerability of INCB053914 in combination with INCB050465 in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

A Safety and Tolerability Study of INCB053914 in Combination With INCB050465 in Diffuse Large B-Cell Lymphoma

A Phase 1b, Multicenter, Open-Label Study of the Safety and Tolerability of INCB053914 in Combination With INCB050465 in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

TEAE is defined as an adverse event reported for the first time or worsening of a pre-existing event after the first dose of study treatment.

Minimum observed plasma concentration during the dosing interval.

Area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration.

Defined as the percentage of participants with a complete remission (CR)/complete metabolic response (CMR) or partial remission (PR)/partial metabolic response (PMR) as defined by investigator assessment per revised Lugano classification criteria for lymphomas.

Defined as the time from first documented evidence of CR/CMR or PR/PMR until disease progression or death from any cause among participants who achieve an objective response, as determined by radiographic disease assessment.

Defined as the time from the date of the first dose of any study drug until the earliest date of disease progression, as determined by radiographic disease assessment, or death from any cause, whichever occurs first.

Incyte Corporation

Symptoms and General Pathology

Heart and Blood Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Multiple Myeloma

Neoplasms, Plasma Cell

Myeloproliferative Disorders

Primary Myelofibrosis

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Azacitidine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Enzyme Inhibitors

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

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

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.

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

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

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

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

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

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

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.

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

I-DAC (Intermediate dose cytarabine)

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

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

Ruxolitinib

Fred Zheng, M.D.

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).

Study of INCB053914 in Subjects With Advanced Malignancies

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

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.

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.

Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay

Part 1 and 2 - INCB053914: 100 mg QD

Part 1 and 2 - INCB053914: 50 mg BID

Part 1 and 2 - INCB053914: 65 mg BID

Part 1 and 2 - INCB053914: 80 mg BID

Part 1 and 2 - INCB053914: 100 mg BID

Part 1 and 2 - INCB053914: 115 mg BID

Part 3 and 4 - INCB053914: 50 mg BID + Cytarabine

Part 3 and 4 - INCB053914: 50 mg BID + Azacitidine

Part 3 and 4 - INCB053914: 80 mg BID + Azacitidine

Part 3 and 4 - INCB053914: 50 mg BID + Ruxolitinib

Part 3 and 4 - INCB053914: 80 mg BID + Ruxolitinib

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

Parts 1 and 2: INCB053914 100 mg QD

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

Parts 1 and 2: INCB053914 50 mg BID

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

Parts 1 and 2: INB053914 65 mg BID

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

Parts 1 and 2: INB053914 80 mg BID

INCB053914 will be self-administered orally twice day s a 100mg immediate release monotherapy dose.

Parts 1 and 2: INB053914 100 mg BID

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

Parts 1 and 2: INB053914 115 mg BID

Combination Treatment Group A: 50 mg BID + 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.

Parts 3 and 4: INCB053914 50 mg BID + Cytarabine

Combination Treatment Group B: Azacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914 50 mg BID.

Parts 3 and 4: INCB053914 50 mg BID + Azacitidine

Combination Treatment Group B: INCB053914 80 mg BID + Azacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914.

Part 3 and 4 - INCB053914 80 mg BID + Azacitidine

Combination Treatment Group C: INCB053914 50 mg BID + Ruxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.

Part 3 and 4: INCB053914 50 mg BID + Ruxolitinib

Combination Treatment Group C: INCB053914 80 mg + Ruxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.

Part 3 and 4: INCB053914 80 mg BID + Ruxolitinib

Total

Age, Continuous

Sex: Female, Male

White/Caucasian

Black/African American

Other

Asian

Native Hawaiian/Pacific Islander

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Unknown

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

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

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

Combination Treatment Group A: INCB053914 50 mg BID + Cytarabine

Combination Treatment Group B: INCB053914 50 mg BID + Azacitidine

Combination Treatment Group B: INCB053914 80 mg BID + Azacitine

Parts 3 and 4: INCB053914 80 mg BID + Azacitine

Combination Treatment Group C: INCB053914 50 mg BID + Ruxolitinib

Parts 3 & 4: INCB 053914 50 mg BID + Ruxolitinib

Combination Treatment Group C: INCB 053914 80 mg BID + Ruxolitinib

Parts 3 & 4: INCB 053914 80 mg + Ruxolitinib

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

Part 4: INCB053914 50 mg BID + Cytarabine)

Part 4 was not opened for enrollment owing to combination regimen not being tolerated in Part 3.

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)

Combination Treatment Group B INCB053914 50 mg BID + Azacitidine

Part 4: INCB053914 50 mg BID + Azacitidine

Combination Treatment Group B: B053914 80 mg BID + Azactidine

Part 4: INB053914 80 mg BID + Azactidine

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 PD evaluable population includes those in the safety population who have at least 1 valid PD measurements at both pre- and postdose.

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

Combination Group A: INCB053914 50 mg BID + Cytarabine

Parts 3 & 4: INCB053914 50 mg BID + Cytarabine

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

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

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

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

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

Combination Treatment Group B: INCB053914 80 mg BID + Azacitidine

Parts 3 & 4: INCB053914 80 mg BID + Azacitidine

Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine

Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine

Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine

Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine

Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine

Combination Treatment Group C: INCB053914 80 mg BID + Ruxolitinib

Parts 3 & 4: INB053914 80 mg BID + Ruxolitinib

Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

Pharmacokinetics: Tmax of INCB053914 Monotherapy

Pharmacokinetics: AUCtau of INCB053914 Monotherapy

Pharmacokinetics: CL/F of INCB053914 Monotherapy

Pharmacokinetics: Cmax of INCB053914 Monotherapy

Ctau was calculated using the predose value on C1D8

Pharmacokinetics: Ctau of INCB053914 Monotherapy

INCB053914 was self-administered orally once a day as a 100mg immediate release monotherapy dose.

INCB053914 was self-administered orally twice day as a 50mg immediate release monotherapy dose.

INCB053914 was self-administered orally twice day as a 65mg immediate release monotherapy dose.

INCB053914 was self-administered orally twice day as a 80mg immediate release monotherapy dose.

INCB053914 was self-administered orally twice day as a 100mg immediate release monotherapy dose.

INCB053914 was self-administered orally twice day as a 115mg immediate release monotherapy dose.

Combination Treatment Group A: 50 mg twice a day + I-DAC (intermediate dose cytarabine) was administered at a dose of 1 g/m2 as an infusion as a combination therapy with INCB053914.

Combination Treatment Group B: INCB053914 50 mg twice a day + Azacitidine was administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914.

Combination Treatment Group B: INCB053914 80 mg BID + Azacitidine was administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914.

Combination Treatment Group C: INCB053914 50 mg + Ruxolitinib was administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.

Combination Treatment Group C: INCB053914 80 mg BID + Ruxolitinib was administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Safety and Tolerability Study of INCB053914 in Combination With INCB050465 in Diffuse Large B-Cell Lymphoma	NCT03688152	Relapsed Diffus... Refractory Diff...	INCB053914 INCB050465	18 Years -	Incyte Corporation
Study of INCB053914 in Subjects With Advanced Malignancies	NCT02587598	Solid Tumors	INCB053914 I-DAC (Intermed... Azacitidine Ruxolitinib	18 Years -	Incyte Corporation
Study of INCB053914 in Subjects With Advanced Malignancies	NCT02587598	Solid Tumors	INCB053914 I-DAC (Intermed... Azacitidine Ruxolitinib	18 Years -	Incyte Corporation

Spots Global Cancer Trial Database for pim kinases

Every month we try and update this database with for pim kinases cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pim kinases

Every month we try and update this database with for pim kinases cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pim kinases cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.