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Initial cohort dose of INCB052793 monotherapy at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria.

INCB052793

Gemcitabine administered intravenously over 30 minutes at the protocol-specified dose and frequency.

gemcitabine

nab-paclitaxel administered intravenously over 30 minutes at the protocol-specified dose and frequency.

nab-paclitaxel

Dexamethasone administered orally at the protocol-specified dose and frequency.

dexamethasone

Carfilzomib administered intravenously at the protocol-specified dose and frequency.

Carfilzomib

Bortezomib administered intravenously or subcutaneously at the protocol-specified dose and frequency.

bortezomib

Lenalidomide administered orally at the protocol-specified dose and frequency.

lenalidomide

Azacitidine administered subcutaneously at the protocol-specified dose and frequency.

azacitidine

INCB052793 tablets administered orally at the protocol specified dose strength and frequency.

Pomalidomide administered orally at the protocol-specified dose and frequency.

pomalidomide

INCB050465 tablets administered orally at the protocol specified dose strength and frequency.

INCB050465

INCB039110 tablets administered orally at the protocol specified dose strength and frequency.

INCB039110

Ekaterine Asatiani, M.D.

This was a study of INCB052793 given to patients with advanced malignancies that was to be conducted in three phases; Phase 1a (Monotherapy) and Phase 1b (Combination Therapy) and Phase 2 (Combination therapy of INCB052793 with azacitidine and itacitinib with azacitidine). Phase 1 had two parts; a dose escalation (Part 1) and an expansion (Part 2).

An Open-Label Study of a Novel JAK-inhibitor, INCB052793, Given to Patients With Advanced Malignancies

A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB052793 in Subjects With Advanced Malignancies

An AE is any untoward medical occurrence in a subject administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization. A TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last dose of study drug.

ORR is defined as the proportion of participants who achieved complete response (CR), CR with incomplete hematologic recovery (CRi), partial response (PR), or hematologic improvement (HI), using the IWG response criteria.

Response rate is defined as the percentage of participants who achieved best overall response (BOR) as determined by IWG response criteria of investigator's assessment. A participant was considered an objective responder based on the following- Solid tumors: participant had a best overall response (BOR) of CR or PR, Lymphoma: participant had a BOR of complete radiologic response/complete metabolic response or partial remission/partial metabolic response, AML: participant had a BOR of CR, CRi, morphological leukemia-free state (MLFS), or PR, MDS: participant had a BOR of CR, PR, or marrow CR, MDS/myeloproliferative neoplasm (MPN): participant had a BOR of CR, PR, or marrow response, MM: participant had a BOR of stringent CR, CR, very good PR, PR, or MR. Subjects are combined by tumor type for this analysis.

Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15). For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.

Tmax is the time to maximum (peak) observed plasma drug concentration. Summary of Steady-State, Day 15, was evaluated by dosing regimen. For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.

AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15). For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.

Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15).

Tmax is the time to maximum (peak) observed plasma drug concentration.

AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15).

Cmax is defined as the maximum observed plasma concentration measured at Day 1.

AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.

Minimum observed plasma concentration measured at steady state (Day 15).

AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15).

AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.

Cmax is defined as the maximum observed plasma concentration measured at cycle 2 Day 1.

Cmin is defined as the minimal observed plasma concentration measured at cycle 2 Day 1

Incyte Corporation

INCB052793 15 mg tablet, orally (PO), once daily (QD) in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 78.3 days ).

Phase 1a TGA - INCB052793 15 mg

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 96.3 days).

Phase 1a TGA - INCB052793 25 mg

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 80.3 days).

Phase 1a TGA - INCB052793 35 mg

INCB052793 50 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 46.5 days).

Phase 1a TGA - INCB052793 50 mg

INCB052793 75 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 459.0 days).

Phase 1a TGA - INCB052793 75 mg

INCB052793 100 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 44.0 days).

Phase 1a TGA - INCB052793 100 mg

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 248.7 days).

Phase 1a TGB - INCB052793 25 mg

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 342.8 days).

Phase 1a TGB - INCB052793 35 mg

INCB052793 50 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 76.3 days).

Phase 1a TGB - INCB052793 50 mg

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with multiple myeloma (MM) in continuous 21 day cycles until they met treatment discontinuation criteria plus Dexamethasone 40 mg, PO, weekly for each 28-day cycle (Up to mean duration of exposure of approximately 53.6 days).

Phase 1b Cohort B - INCB052793 25 mg + Dexamethasone 40 mg

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS) in continuous 21 day cycles until they met treatment discontinuation criteria plus Azacitidine 75 mg/m\^2, subcutaneous (SC) injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 28-day cycle (Up to mean duration of exposure of approximately 151.2 days).

Phase 1b Cohort F - INCB052793 25 mg + Azacytidine 75 mg/m^2

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with AML/MDS in continuous 21 day cycles until they met treatment discontinuation criteria Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 28-day cycle (Up to mean duration of exposure of approximately 142.1 days).

Phase 1b Cohort F - INCB052793 35 mg + Azacytidine 75 mg/m^2

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with hypomethylating agent-refractory (HMA)-refractory AML and high-risk MDS in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 28-day cycle (Up to mean duration of exposure of approximately 86.2 days).

Phase 2 Cohort I - INCB052793 35 mg + Azacytidine 75 mg/m^2

Itacitinib 300 mg sustained-release tablet, PO, QD in the fasted state in participants with HMA-refractory AML and high-risk MDS in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 28-day cycle (Up to mean duration of exposure of approximately 143 days).

Phase 2 Cohort J - Itacitinib 300 mg + Azacitidine 75 mg/m^2

INCB052793 15 mg tablet, orally (PO), once daily (QD) in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria

INCB052793 50 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 75 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 100 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 50 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria.

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with multiple myeloma (MM) in continuous 21 day cycles until they met treatment discontinuation criteria plus Dexamethasone 40 mg, PO, weekly for each 21-day cycle.

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS) in continuous 21 day cycles until they met treatment discontinuation criteria plus Azacitidine 75 mg/m\^2, subcutaneous (SC) injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle.

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with AML/MDS in continuous 21 day cycles until they met treatment discontinuation criteria Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with hypomethylating agent-refractory (HMA)-refractory AML and high-risk MDS in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle

Itacitinib 300 mg sustained-release tablet, PO, QD in the fasted state in participants with HMA-refractory AML and high-risk MDS in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle

• Phase 2 Cohort J - Itacitinib 300 mg + Azacitidine 75 mg/m^2

Total

Age, Continuous

Sex: Female, Male

White/Caucasian

Black/African-American

American-Indian/Alaska Native

Other

Missing

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Unknown

The safety evaluable population included all subjects enrolled in the study who receivedat least 1 dose of study treatment.

Study Director

The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

TEAE

INCB052793 15 mg tablet, orally (PO), once daily (QD) in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria

INCB052793 50 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria

INCB052793 75 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria

INCB052793 100 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria

INCB052793 50 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with multiple myeloma (MM) in continuous 21 day cycles until they met treatment discontinuation criteria plus Dexamethasone 40 mg, PO, weekly for each 21-day cycle

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS) in continuous 21 day cycles until they met treatment discontinuation criteria plus Azacitidine 75 mg/m\^2, subcutaneous (SC) injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle

Safety evaluable population included all participants exposed to ≥ 1 dose of study drug.

Phase 1a and 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)

Confidence Intervals for ORR were calculated based on the exact method for binomial distributions. There were no comparison between treatment groups.

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with HMA-refractory AML in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle.

Phase 2 Cohort I-INCB052793 +Azacytidine (AML)

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with high-risk MDS in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle.

Phase 2 Cohort I-INCB052793 +Azacytidine (MDS)

Itacitinib 300 mg sustained-release tablet, PO, QD in the fasted state in participants with HMA-refractory AML in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle.

Phase 2 Cohort J-Itacitinib +Azacitidine (AML)

Itacitinib 300 mg sustained-release tablet, PO, QD in the fasted state in participants with high-risk MDS in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle .

Phase 2 Cohort J-Itacitinib +Azacitidine (MDS)

Efficacy evaluable population included all participants exposed to ≥ 1 dose of study drug.

Phase 2: Objective Response Rate (ORR) in Hematological Malignancies

Confidence Intervals for response were calculated based on the exact method for binomial distributions. There were no comparison between treatment groups.

INCB052793 tablet, orally (PO), once daily (QD) in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria.

Phase 1a TGA - INCB052793 in Solid Tumors

INCB052793 tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21 day cycles until they met treatment discontinuation criteria.

Phase 1a TGB - INCB052793 in Lymphoma

Phase 1a TGB - INCB052793 in MDS/MPN

Phase 1a TGB - INCB052793 in MM

Phase 1b Cohort B - INCB052793 + Dexamethasone in MM

Phase 1b Cohort F-INCB052793 +Azacytidine in AML

Phase 1b Cohort F-INCB052793 +Azacytidine in MDS

Phase 1b Cohort F-INCB052793 +Azacytidine in MDS/MPN

Phase 1A and 1B: Percentage of Participants With Response as Determined by Investigator's Assessment

The analysis of the endpoint was descriptive i.e. no statistical hypothesis test was performed.

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with hypomethylating agent-refractory (HMA)-refractory AML and high-risk MDS in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle.

Itacitinib 300 mg sustained-release tablet, PO, QD in the fasted state in participants with HMA-refractory AML and high-risk MDS in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle.

Phase 2: Number of Participants With at Least One TEAE and SAE

INCB052793 15 mg tablet, orally (PO), once daily (QD) in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 78.3 days ).

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21 day cycles until they met treatment discontinuation criteria (Up to mean duration of exposure of approximately 96.3 days).

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with AML/MDS in continuous 21 day cycles until they met treatment discontinuation criteria Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle.

The PK evaluable population includes all subjects who received at least 1 dose of study treatment and provided serial samples for PK analysis

Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration for INCB052793

Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for INCB052793

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with multiple myeloma (MM) in continuous 21 day cycles until they met treatment discontinuation criteria plus Dexamethasone 40 mg, PO, weekly for each 21-day cycle .

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with hypomethylating agent-refractory (HMA)-refractory AML and high-risk MDS in continuous 21 day cycles until they met treatment discontinuation criteria. Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle .

Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793

Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration of Itacitinib

Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for Itacitinib

Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for Itacitinib

INCB052793 35 mg tablet in combination with Azacitidine or Itacitinib 300mg in combination with Azacitidine

Phase 1a Part 2 Expasion Cohort- INCB052793

Data was not collected as no participants were enrolled in Part 2 of the study.

Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793

Data was not collected as no participants were enrolled in Part 2 of the study

Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793

Phase 1a, Part 2: AUC[0-t]: Area Under the Plasma Concentration-Time Curve From Time 0 To the Last Measurable Concentration at Time t

Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval

Phase 1a, Part 2: AUC[0-t]: Area Under the Plasma Concentration-Time Curve From Time 0 To the Last Measurable Concentration at Time

Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21day cycles until they met treatment discontinuation criteria

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with advanced or metastatic solid tumors treated in continuous 21day cycles until they met treatment discontinuation criteria.

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with advanced hematologic malignancies treated in continuous 21day cycles until they met treatment discontinuation criteria.

INCB052793 25 mg tablet, PO, QD in the fasted state in participants with acute myeloid leukemia (AML)/ myelodysplastic syndrome (MDS) in continuous 21day cycles until they met treatment discontinuation criteria plus Azacitidine 75 mg/m\^2, subcutaneous (SC) injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 21-day cycle.

INCB052793 35 mg tablet, PO, QD in the fasted state in participants with AML/MDS in continuous 21 day cycles until they met treatment discontinuation criteria Azacitidine 75 mg/m\^2, SC injection for 5 days, then no treatment for 2 days, then 75 mg/m\^2 for 2 days for each 28-day cycle.

Spots Global Cancer Trial Database for An Open-Label Study of a Novel JAK-inhibitor, INCB052793, Given to Patients With Advanced Malignancies

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Study Description

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