The primary objectives of this study are to characterize the safety and tolerability and determine the maximum tolerated dose (MTD) or recommended dose for phase 2 study (RDP2) of alobresib as a monotherapy in participants with advanced solid tumors and lymphomas, and in combination with exemestane or fulvestrant in participants with advanced estrogen receptor positive breast cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle
Tablets administered orally once daily on Cycle 1 Day 1 of 28 days cycle
Administered intramuscularly on Cycle 1 Day 1 of 28 days cycle and every 28 days
Unnamed facility
Scottsdale, Arizona, United States
Unnamed facility
Fort Wayne, Indiana, United States
Unnamed facility
Goshen, Indiana, United States
Unnamed facility
San Antonio, Texas, United States
Number of Participants Experiencing Dose Limiting Toxicities (DLTs)
A DLT was a toxicity, considered possibly related to alobresib, and which occurred during DLT assessment window (Day 1 through Cycle 1 Day 28) in each cohort: Grade ≥ 4 neutropenia (absolute neutrophil count \[ANC\] \< 500/mm\^3); Grade ≥3 neutropenia (ANC\< 1000/mm\^3) with fever (a single temperature of \> 38.3°C or a sustained temperature of ≥ 38°C for more than 1 hour \[hr\]); Grade ≥ 3 thrombocytopenia; Grade ≥ 2 bleeding; Grade ≥ 3 non hematologic toxicity, except Grade 3 nausea or emesis with maximum duration of 48 hrs on adequate medical therapy and Grade 3 diarrhea which persists for \< 72 hrs in absence of maximal medical therapy; Grade ≥ 2 non hematologic treatment-emergent adverse event (TEAE) of potential clinical significance; treatment interruption ≥ 7 days due to unresolved toxicity; and any Grade 3 or 4 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to alobresib.
Time frame: Baseline (Day 1) up to 28 days
Pharmacokinetic (PK) Parameter: Cmax of Alobresib
Cmax is defined as the maximum concentration of the drug.
Time frame: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)
PK Parameter: Ctau of Alobresib
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Time frame: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Day 8 (1 Cycle = 28 days)
PK Parameter: AUC0-24 of Alobresib
AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hrs.
Time frame: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)
PK Parameter: AUCtau of Alobresib
AUCtau is defined as the concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time frame: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Day 8 (1 Cycle = 28 days)
PK Parameter: Tmax of Alobresib
Tmax is defined as the time (observed time point) of Cmax.
Time frame: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)
PK Parameter: t1/2 of Alobresib
t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Due to short sampling period of the terminal elimination phase in these cohorts t1/2 values should be interpreted with caution.
Time frame: Cycle 1: Predose (0 hr), 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hrs postdose on Days 1 and 8 (1 Cycle = 28 days)
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