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

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

Sponsors

Lead sponsor: Incyte Corporation

Source 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).

Overall Status Terminated
Start Date September 10, 2014
Completion Date February 27, 2019
Primary Completion Date February 27, 2019
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
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)
Phase 2: Objective Response Rate (ORR) in Hematological Malignancies Baseline through end of study (Up to approximately 4.5 years)
Secondary Outcome
Measure Time Frame
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)
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)
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
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
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
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
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
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
Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793 Cycle 1, Day 1
Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793 Cycle 1, 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 t Cycle 1, Day 1
Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793 Cycle 1, Day 15
Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval Cycle 1, Day 15
Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793 Cycle 1, Day 15
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 1, Day 15
Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793 Cycle 1, Day 15
Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793 Cycle 2, Day 1
Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval Cycle 2, Day 1
Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793 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
Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793 Cycle 2, Day 1
Enrollment 83
Condition
Intervention

Intervention type: Drug

Intervention name: INCB052793

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

Arm group label: Phase 1a: INCB052793 Monotherapy

Intervention type: Drug

Intervention name: gemcitabine

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

Arm group label: Phase 1b: INCB052793 Combination Therapy

Other name: Gemzar®

Intervention type: Drug

Intervention name: nab-paclitaxel

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

Arm group label: Phase 1b: INCB052793 Combination Therapy

Other name: Abraxane®

Intervention type: Drug

Intervention name: dexamethasone

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

Arm group label: Phase 1b: INCB052793 Combination Therapy

Intervention type: Drug

Intervention name: Carfilzomib

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

Arm group label: Phase 1b: INCB052793 Combination Therapy

Other name: Kyprolis®

Intervention type: Drug

Intervention name: bortezomib

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

Arm group label: Phase 1b: INCB052793 Combination Therapy

Other name: Velcade®

Intervention type: Drug

Intervention name: lenalidomide

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

Arm group label: Phase 1b: INCB052793 Combination Therapy

Other name: Revlimid®

Intervention type: Drug

Intervention name: azacitidine

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

Other name: Vidaza®

Intervention type: Drug

Intervention name: INCB052793

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

Intervention type: Drug

Intervention name: pomalidomide

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

Arm group label: Phase 1b: INCB052793 Combination Therapy

Other name: Pomalyst®

Intervention type: Drug

Intervention name: INCB050465

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

Arm group label: Phase 1b: INCB052793 Combination Therapy

Intervention type: Drug

Intervention name: INCB039110

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

Arm group label: Phase 2: INCB052793 and itacitinib Combination Therapy

Other name: itacitinib

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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Ekaterine Asatiani, M.D. Study Director Incyte Corporation
Location
facility
| Birmingham, Alabama, United States
| West Hollywood, California, United States
| New Haven, Connecticut, United States
| Atlanta, Georgia, United States
| Chicago, Illinois, United States
| Indianapolis, Indiana, United States
| Hackensack, New Jersey, United States
| New York, New York, United States
| Durham, North Carolina, United States
| Portland, Oregon, United States
| Greenville, South Carolina, United States
Site 2 | Nashville, Tennessee, United States
| Nashville, Tennessee, United States
| Dallas, Texas, United States
Location Countries

United States

Verification Date

April 2020

Responsible Party

Responsible party type: Sponsor

Has Expanded Access Yes
Condition Browse
Number Of Arms 3
Arm Group

Arm group label: Phase 1a: INCB052793 Monotherapy

Arm group type: Experimental

Arm group label: Phase 1b: INCB052793 Combination Therapy

Arm group type: Experimental

Arm group label: Phase 2: INCB052793 and itacitinib Combination Therapy

Arm group type: Experimental

Study Design Info

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov