A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB052793 in Subjects With Advanced Malignancies
Overview
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Incyte Corporation
- Enrollment
- 83
- Locations
- 1
- Primary Endpoint
- Phase 1a and 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
- •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
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
Arms & Interventions
Phase 1a: INCB052793 Monotherapy
Intervention: INCB052793 (Drug)
Phase 1b: INCB052793 Combination Therapy
Intervention: gemcitabine (Drug)
Phase 1b: INCB052793 Combination Therapy
Intervention: nab-paclitaxel (Drug)
Phase 1b: INCB052793 Combination Therapy
Intervention: dexamethasone (Drug)
Phase 1b: INCB052793 Combination Therapy
Intervention: Carfilzomib (Drug)
Phase 1b: INCB052793 Combination Therapy
Intervention: bortezomib (Drug)
Phase 1b: INCB052793 Combination Therapy
Intervention: lenalidomide (Drug)
Phase 1b: INCB052793 Combination Therapy
Intervention: azacitidine (Drug)
Phase 1b: INCB052793 Combination Therapy
Intervention: INCB052793 (Drug)
Phase 1b: INCB052793 Combination Therapy
Intervention: pomalidomide (Drug)
Phase 1b: INCB052793 Combination Therapy
Intervention: INCB050465 (Drug)
Phase 2: INCB052793 and itacitinib Combination Therapy
Intervention: azacitidine (Drug)
Phase 2: INCB052793 and itacitinib Combination Therapy
Intervention: INCB052793 (Drug)
Phase 2: INCB052793 and itacitinib Combination Therapy
Intervention: INCB039110 (Drug)
Outcomes
Primary Outcomes
Phase 1a and 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Time Frame: 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
Time Frame: 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 Outcomes
- 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, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793(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))
- 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: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval(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: 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 t(Cycle 1, Day 1)
- Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793(Cycle 2, Day 1)