This is a multicenter, open label, nonrandomized, sequential dose escalation, multiple dose study designed to evaluate the safety, toxicity, and pharmacokinetics (PK) as well as preliminary efficacy of BTX-1188 orally administered in subjects with advanced malignancies.
Study BTX-1188-001 is a multicenter, open label, nonrandomized, sequential dose escalation study to evaluate the safety, toxicity, PK, and preliminary efficacy of BTX-1188. Dose escalation will be conducted in subjects with acute myeloid leukemia (AML) and advanced lymphoid and solid tumors. Based on the results of the dose escalation, a recommended Phase 2 dose will be determined.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
8
One 28 day cycle of treatment will consist of 4 weeks of treatment with BTX-1188 administered orally per dosing schedule.
City of Hope Medical Center
Duarte, California, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
The Christ Hospital
Cincinnati, Ohio, United States
M.D. Anderson Cancer Center
Houston, Texas, United States
To evaluate the Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] with BTX-1188 in subjects with advanced malignancies
To examine the incidence of clinical and laboratory adverse events after multiple doses of BTX-1188
Time frame: From first dose of BTX-1188 through 30 days after the last BTX-1188 treatment
To determine the recommended Phase 2 dose (RP2D) of BTX-1188 in subjects with advanced malignancies
To assess number of patients experiencing dose-limiting toxicities (DLTs)
Time frame: At the end of Cycle 1 (each cycle is 28 days)
Maximum Plasma Concentration of BTX-1188
To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of BTX-1188
Time frame: PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, and 8 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Peak Plasma Concentration of BTX-1188
To evaluate the observed time of peak concentration (Tmax) after single and repeated oral, once daily doses of BTX-1188
Time frame: PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, and 8 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Area under the plasma concentration of BTX-1188
To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of BTX-1188.
Time frame: PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, and 8 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Half-life of BTX-1188
To evaluate the half-life of BTX-1188 after single and repeated oral, once daily doses of BTX-1188.
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Time frame: PK samples are collected at pre-dose and post-dose at 1, 2, 3, 5, and 8 hours on Days 1 and 5 of Cycle 1 (each cycle is 28 days).
Objective response rate (ORR)
To evaluate the objective response rate (ORR) as determined by the specific disease response criteria.
Time frame: Up to 2 years after the last treatment or upon death.
Best response
To evaluate the complete remission/response \[CR\], CR with incomplete blood count recovery \[CRi\], morphologic leukemia free state \[MLFS\], partial remission/response \[PR\], stable disease or progression as determined by the specific disease response criteria.
Time frame: For subjects with AML, response will be evaluated at the end of each cycle (each cycle is 28 days) and after the last dose of BTX-1188 (approximately 36 months). For subjects with NHL or solid tumors, response will be evaluated every 8-weeks.
Disease Control Rate (DCR)
To evaluate the DCR (response + stable disease) as determined by the specific disease response criteria.
Time frame: For subjects with AML, response will be evaluated at the end of each cycle (each cycle is 28 days) and after the last dose of BTX-1188 (approximate 36 months). For subjects with NHL or solid tumors, response will be evaluated every 8-weeks.
Duration of response (DoR)
To evaluate the duration of response (DoR), defined as time from the date of first documentation of response to the date of the first documentation of progressive disease (PD), or death due to any cause.
Time frame: Up to 2 years after the last treatment or upon death.
Progression free survival (PFS)
To examine the the progression free survival (PFS), defined as time from the date of first dose of study treatment to the first date of documentation of PD, or death due to any cause.
Time frame: Up to 2 years after the last treatment or upon death.
Overall survival (OS)
To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause.
Time frame: Up to 2 years after the last treatment or upon death.