This is a first-in-human (FIH), multicenter, open-label Phase I dose escalation study to evaluate the safety and preliminary efficacy of the TT-01488 tablet, a non-covalent reversible BTK inhibitor, for the treatment of adult patients with B-cell malignancies.
The study will consist of two parts, dose escalation and dose expansion. A modified 3+3 design will be used to guide the dose escalation and the determination of the dose recommended for dose expansion (DRDE). A sentinel cohort comprising of one subject will be enrolled at a starting dose of 50 mg q.d. Subsequently, patients will be enrolled according to the standard 3+3 dose escalation design to determine the DRDE. Once the DRDE has been selected, TT-01488 of DRDE will be further tested in the dose expansion cohort to verify the safety and preliminary efficacy as observed in the dose escalation cohorts. A recommended Phase II dose (RP2D) may be determined based on the totality of safety, pharmacokinetics, and efficacy data from the dose escalation cohorts and dose expansion cohort.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
37
TT-01488 tablet will be administered orally once daily per protocol defined schedule.
Gabrail Cancer Center
Canton, Ohio, United States
RECRUITINGThe University of Texas MD Anderson Cancer Center (MDACC)
Houston, Texas, United States
NOT_YET_RECRUITINGDose-Limiting Toxicity (DLT) of TT-01488
Safety and tolerability of TT-01488 as a single agent
Time frame: Up to 28 days after first dose
Dose recommend for dose expansion (DRDE)
Safety and tolerability of TT-01488 as a single agent
Time frame: 1 - 1.5 years
Maximum Tolerated Dose (MTD), if reached, of TT-01488
Safety and tolerability of TT-01488 as a single agent
Time frame: Up to 28 days after first dose
Number of participants with treatment-related adverse events (AEs)
Safety and tolerability of TT-01488 as a single agent. AEs will be assessed per CTCAE v5.0 and may include, but is not limited to, clinically abnormal laboratory tests, physical exams, vital signs, electrocardiograms, and ECOG performance status.
Time frame: 1 - 1.5 years
Objective Response Rate (ORR)
Preliminary efficacy profile of TT-01488 as a single agent
Time frame: 1 - 1.5 years
Disease Control Rate (DCR)
Preliminary efficacy profile of TT-01488 as a single agent
Time frame: 1 - 1.5 years
Duration of Response (DOR)
Preliminary efficacy profile of TT-01488 as a single agent
Time frame: 1 - 1.5 years
Progression free survival (PFS)
Preliminary efficacy profile of TT-01488 as a single agent
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 1 - 1.5 years
Overall survival (OS)
Preliminary efficacy profile of TT-01488 as a single agent
Time frame: 1 - 1.5 years
Recommended Phase 2 dose (RP2D)
Safety and tolerability of TT-01488 as a single agent
Time frame: 1 - 1.5 years
Area under the concentration time curve (AUC 0-last)
Pharmacokinetic (PK) profile of TT-01488 as a single agent
Time frame: 1 - 1.5 years
Maximum plasma concentration (Cmax)
Pharmacokinetic (PK) profile of TT-01488 as a single agent
Time frame: 1 - 1.5 years
Time to Maximum Plasma Concentration (Tmax)
Pharmacokinetic (PK) profile of TT-01488 as a single agent
Time frame: 1 - 1.5 years
Half-life (T1/2)
Pharmacokinetic (PK) profile of TT-01488 as a single agent
Time frame: 1 - 1.5 years
Mean Residence Time (MRT)
Pharmacokinetic (PK) profile of TT-01488 as a single agent
Time frame: 1 - 1.5 years
Volume of Distribution (Vd)
Pharmacokinetic (PK) profile of TT-01488 as a single agent
Time frame: 1 - 1.5 years