An Open-Label, Dose-Escalation Study of INCB054329 in Patients With Advanced Malignancies

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.

Time frame: up to 30 days

Population: The safety population included all enrolled participants who received at least 1 dose of INCB054329.

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.

Time frame: Summary of steady-state PK parameters by dosing regimen at Day 15

Population: All enrolled patients who received at least 1 dose of study medication and provided at least 1 plasma sample were included.

Cl/F is the apparent oral dose clearance measured at steady state (Day 15). Study drug was administered with 240 mL of water.

Time frame: Summary of steady-state PK parameters by dosing regimen at Day 15

Population: All enrolled patients who received at least 1 dose of study medication and provided at least 1 plasma sample were included.

Defined as the time from earliest date of disease response until earliest date of disease progression or death.

Time frame: Baseline through end of study, up to 6 months

Population: As a result of early termination of the study, there are no participants that are responders and therefore DOR was not achieved.

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 frame: Summary of steady-state PK parameters by dosing regimen at Day 15

Population: All enrolled patients who received at least 1 dose of study medication and provided at least 1 plasma sample were included.

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.

Time frame: Summary of steady-state PK parameters by dosing regimen at Day 15

Population: All enrolled patients who received at least 1 dose of study medication and provided at least 1 plasma sample were included.

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).

Time frame: Baseline through end of study, up to 6 months

Population: As a result of early termination of the study, only participants in Part 2 of the study were evaluated; Treatment Group C was not evaluated due to early termination from the study.

OS is defined as the time from the date of randomization to the date of the participant's death.

Time frame: Baseline through end of study, up to 6 months for participants in Part 2

Population: As a result of early termination of the study, only participants in Part 2 of the study were evaluated; Treatment Group C was not evaluated due to early termination from the study.

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.

Time frame: Day 15 in all cohorts

Population: 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.

PFS is the time from start of study treatment to first documentation of progression, or to death due to any cause, whichever comes first

Time frame: Baseline through end of study, up to 6 months

Population: As a result of early termination of the study, only participants in Part 2 of the study were evaluated; Treatment Group C was not evaluated due to early termination from the study.

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.

Time frame: Summary of steady-state PK parameters by dosing regimen at Day 15

Population: All enrolled patients who received at least 1 dose of study medication and provided at least 1 plasma sample were included.