An Open-Label, Dose-Escalation Study of INCB054329 in Patients With Advanced Malignancies
- Conditions
- Solid Tumors and Hematologic Malignancy
- Interventions
- Drug: INCB054329 Monotherapy
- Registration Number
- NCT02431260
- Lead Sponsor
- Incyte Corporation
- Brief Summary
This was a study of INCB054329 given to patients with advanced malignancies that were conducted in three treatment groups. Each treatment group had a dose escalation (Part 1) and a dose expansion (Part 3), two of the treatment groups also had an intra-patient dose titration (Part 2).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 69
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Confirmed diagnosis of advanced malignancy:
- Treatment Group A (TGA): Part 1 and Part 2: Any advanced solid tumor or lymphoma; Part 3: Histologically confirmed disease in specific solid tumors and lymphomas
- Treatment Group B (TGB): Acute Leukemia (Part 3 - acute myeloid leukemia [AML] only), myelodysplastic syndrome (MDS), myelodysplastic /myeloproliferative neoplasms (MDS/MPN) and myelofibrosis (MF)
- Treatment Group C (TGC): Multiple myeloma
-
Progressed following at least 1 line of prior therapy and there is no further approved therapy available that has been demonstrated to prolong survival (including subjects who are intolerant to the approved therapy)
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 in Parts 1 and 2 dose escalation and titration, and 0, 1, 2 in Part 3 dose expansion
Key
-
Inadequate hematopoietic, liver, endocrine or renal function
-
Receipt of anticancer medications or investigational drugs within the following interval before the first administration of study drug:
- < 6 weeks for mitomycin-C or nitrosoureas
- < 5 half-lives or 14 days, whichever is longer, for any investigational agent (for any indication)
- < 28 days for any antibodies or biological therapies
- < 5 half-lives for all other anticancer medications, or sponsor approval
-
Prior radiotherapy within 2 weeks prior to first dose of study drug
-
Untreated brain or central nervous system (CNS) metastases
-
Type 1 diabetes or uncontrolled Type 2 diabetes
-
Any sign of clinically significant bleeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description INCB054329 Monotherapy INCB054329 Monotherapy -
- Primary Outcome Measures
Name Time Method Number of Participants With a Treatment-emergent Adverse Event (TEAE) up to 30 days TEAE is defined as an adverse event reported for the first time or worsening of a pre-existing event after the first dose of study treatment.
- Secondary Outcome Measures
Name Time Method Maximum Plasma Concentration (Cmax) Analysis of INCB054329 Summary of steady-state PK parameters by dosing regimen at Day 15 Cmax is defined as the maximum observed serum concentration measured at steady state (Day 15).
Study drug was administered with 240 mL of water. Summary of Steady-State, Day 15, was evaluated by dosing regimen.Time to Maximum Plasma Concentration (Tmax) Analysis of INCB054329 Summary of steady-state PK parameters by dosing regimen at Day 15 Tmax is the time to maximum (peak) drug serum concentration. Study drug was administered with 240 mL of water. Summary of Steady-State, Day 15, was evaluated by dosing regimen.
Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) Analysis of INCB054329 Summary of steady-state PK parameters by dosing regimen at Day 15 Minimum observed plasma concentration measured at steady state (Day 15). Study drug was administered with 240 mL of water. Summary of Steady-State, Day 15, was evaluated by dosing regimen.
AUC0-t Analysis of INCB054329 Summary of steady-state PK parameters by dosing regimen at Day 15 AUC0-t is the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15).
Study drug was administered with 240 mL of water.Cl/F Analysis of INCB054329 Summary of steady-state PK parameters by dosing regimen at Day 15 Cl/F is the apparent oral dose clearance measured at steady state (Day 15). Study drug was administered with 240 mL of water.
Objective Response Rate (ORR) Baseline through end of study, up to 6 months Defined as the percentage of subjects having complete response (CR) or partial response (PR). The best overall response was defined as the best response recorded before and including the first event of Progressive disease (PD).
Pharmacodynamics (PD) Analysis - Total c-Myc % Inhibition Versus INCB054329 Day 15 in all cohorts The half maximal inhibitory concentration (IC50) of INCB054329 was measured. The maximal inhibition of total c-Myc was correlated to the level of drug exposure and demonstrated a high degree of interparticipant variability, parallel to the PK data.
The measure was performed as a value across all cohorts. The entire dose escalation data set was used to create the relationship curve. Analysis of individual cohorts contained too few subjects and was biased toward one region of the curve so that the relationship was poorly defined.
Individual data points from all subjects were subjected to a nonlinear least squares regression analysis with no weighting, resulting in a sigmoidal dose response curve defining the relationship. The numerical value given is the projected INCB0054329 concentration in nM that produced 50% inhibition of c-myc expression.Duration of Response (DOR) Baseline through end of study, up to 6 months Defined as the time from earliest date of disease response until earliest date of disease progression or death.
Progression Free Survival (PFS) Baseline through end of study, up to 6 months PFS is the time from start of study treatment to first documentation of progression, or to death due to any cause, whichever comes first
Overall Survival (OS) Baseline through end of study, up to 6 months for participants in Part 2 OS is defined as the time from the date of randomization to the date of the participant's death.
Trial Locations
- Locations (12)
John Hopkins
🇺🇸Baltimore, Maryland, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Washington University School of Medicine in St. Louis
🇺🇸Saint Louis, Missouri, United States
The University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of California, San Francisco, Medical Center at Mount Zion
🇺🇸San Francisco, California, United States
Horizon Oncology Center
🇺🇸Lafayette, Indiana, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Sarah Cannon Research Institute Research Center
🇺🇸Denver, Colorado, United States