Clinical trial NCT02265510: An Open-Label Study of a Novel JAK-inhibitor, INCB052793, Given to Patients With Advanced Malignancies
Official title: A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB052793 in Subjects With Advanced Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Solid Tumors
Advanced Malignancies
Metastatic Cancer
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2014-10-16
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Phase 1a and 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 3.4 years)
measure: Phase 2: Objective Response Rate (ORR) in Hematological Malignancies
timeFrame: Baseline through end of study (Up to approximately 4.5 years)
Secondary outcomes:
measure: Phase 1A and 1B: Percentage of Participants With Response as Determined by Investigator's Assessment
timeFrame: Baseline through end of study (Up to approximately 4.5 years)
measure: Phase 2: Number of Participants With at Least One TEAE and SAE
timeFrame: From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 1.3 years)
measure: Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
timeFrame: 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
measure: Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
timeFrame: 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
measure: Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793
timeFrame: 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
measure: Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration of Itacitinib
timeFrame: 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
measure: Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for Itacitinib
timeFrame: 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
measure: Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for Itacitinib
timeFrame: 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
measure: Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
timeFrame: Cycle 1, Day 1
measure: Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
timeFrame: Cycle 1, Day 1
measure: 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
timeFrame: Cycle 1, Day 1
measure: Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
timeFrame: Cycle 1, Day 15
measure: Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval
timeFrame: Cycle 1, Day 15
measure: Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
timeFrame: Cycle 1, Day 15
measure: Phase 1a, Part 2: AUC[0-t]: Area Under the Plasma Concentration-Time Curve From Time 0 To the Last Measurable Concentration at Time
timeFrame: Cycle 1, Day 15
measure: Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793
timeFrame: Cycle 1, Day 15
measure: Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
timeFrame: Cycle 2, Day 1
measure: Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval
timeFrame: Cycle 2, Day 1
measure: Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
timeFrame: Cycle 2, Day 1
measure: Phase 1a, Part 2: AUC[0-t]: Area Under the Plasma Concentration-Time Curve From Time 0 To the Last Measurable Concentration at Time
timeFrame: Cycle 2, Day 1
measure: Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793
timeFrame: Cycle 2, Day 1
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: West Hollywood
country: United States
state: California
city: New Haven
country: United States
state: Connecticut
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Hackensack
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Portland
country: United States
state: Oregon
city: Greenville
country: United States
state: South Carolina
city: Nashville
country: United States
facility: Site 2
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
Study officials:
affiliation: Incyte Corporation
name: Ekaterine Asatiani, M.D.
role: STUDY_DIRECTOR
References: