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

Phase 1

Terminated

Conditions: Advanced Malignancies
Solid Tumors
Metastatic Cancer

Interventions: Drug: azacitidine
Drug: gemcitabine
Drug: INCB052793
Drug: nab-paclitaxel
Drug: INCB039110
Drug: dexamethasone
Drug: Carfilzomib
Drug: bortezomib
Drug: lenalidomide
Drug: pomalidomide
Drug: INCB050465

Registration Number: NCT02265510

Lead Sponsor: Incyte Corporation

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 83

Inclusion Criteria

Phase 1a

Aged 18 years or older
Histologically or cytologically confirmed solid tumor or hematologic malignancy
Life expectancy of 12 weeks or longer
Must have received ≥ 1 prior treatment regimen
Must not be a candidate for potentially curative or standard of care approved therapy

Phase 1b

Aged 18 years or older
Cohort A: Histologically or cytologically confirmed pancreatic adenocarcinoma, triple-negative breast cancer, urothelial cancer with at least 1 measurable or evaluable target lesion
Cohorts B, C, D, E and G: Histologically confirmed multiple myeloma and measureable/evaluable disease
Cohort F: Confirmed acute myeloid leukemia or myelodysplastic syndrome
Cohort H: Individuals diagnosed with lymphoma
Prior therapy:
- Cohort A: No more than 1 prior chemotherapy regimen for advanced or metastatic disease (not including neoadjuvant and/or adjuvant therapy)
- Cohorts B, C, D, E and G: Must have relapsed from or have been refractory to ≥ 2 prior treatment regimens
- Cohort F: May have received any number of prior treatment regimens or be treatment-naïve
- Cohort H: Must have relapsed from or have been refractory to available treatments

Phase 2

Aged 18 years or older
Cohorts I and J: Confirmed acute myeloid leukemia or high risk myelodysplastic syndrome
Prior therapy:
- Cohorts I and J: Must have failed prior therapy with a hypomethylating agent (HMA)

Exclusion Criteria

Prior receipt of a JAK1 inhibitor (Phase 1a only)
Known active central nervous system metastases and/or carcinomatous meningitis
Eastern Cooperative Oncology Group (ECOG) performance status > 2
Any known contraindications to the use of gemcitabine, nab-paclitaxel, dexamethasone, carfilzomib, bortezomib, lenalidomide, azacitidine, pomalidomide or PI3Kδ inhibitor (Phase 1b and Phase 2 only, as appropriate to treatment cohort)
Known human immunodeficiency virus infection, or evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2: INCB052793 and itacitinib Combination Therapy	INCB052793	-
Phase 1b: INCB052793 Combination Therapy	INCB050465	-
Phase 1b: INCB052793 Combination Therapy	pomalidomide	-
Phase 2: INCB052793 and itacitinib Combination Therapy	INCB039110	-
Phase 1b: INCB052793 Combination Therapy	nab-paclitaxel	-
Phase 2: INCB052793 and itacitinib Combination Therapy	azacitidine	-
Phase 1b: INCB052793 Combination Therapy	bortezomib	-
Phase 1a: INCB052793 Monotherapy	INCB052793	-
Phase 1b: INCB052793 Combination Therapy	gemcitabine	-
Phase 1b: INCB052793 Combination Therapy	dexamethasone	-
Phase 1b: INCB052793 Combination Therapy	Carfilzomib	-
Phase 1b: INCB052793 Combination Therapy	lenalidomide	-
Phase 1b: INCB052793 Combination Therapy	azacitidine	-
Phase 1b: INCB052793 Combination Therapy	INCB052793	-

Primary Outcome Measures

Name	Time	Method
Phase 1a and 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)	From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 3.4 years)	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.
Phase 2: Objective Response Rate (ORR) in Hematological Malignancies	Baseline through end of study (Up to approximately 4.5 years)	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.

Secondary Outcome Measures

Name	Time	Method
Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for INCB052793	Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2	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.
Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793	Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2	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.
Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration of Itacitinib	Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2	Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15).
Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for Itacitinib	Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2	Tmax is the time to maximum (peak) observed plasma drug concentration.
Phase 2: Number of Participants With at Least One TEAE and SAE	From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 1.3 years)	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.
Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration for INCB052793	Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2	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.
Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793	Cycle 2, Day 1	Cmax is defined as the maximum observed plasma concentration measured at cycle 2 Day 1.
Phase 1A and 1B: Percentage of Participants With Response as Determined by Investigator's Assessment	Baseline through end of study (Up to approximately 4.5 years)	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.
Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for Itacitinib	Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2	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).
Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval	Cycle 2, Day 1	Cmin is defined as the minimal observed plasma concentration measured at cycle 2 Day 1
Phase 1a, Part 2: AUC[0-t]: Area Under the Plasma Concentration-Time Curve From Time 0 To the Last Measurable Concentration at Time	Cycle 2, Day 1	AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793	Cycle 2, Day 1	Tmax is the time to maximum (peak) observed plasma drug concentration.
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	Cycle 1, Day 1	AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793	Cycle 2, Day 1	AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.