This study is a multicenter, open-label, phase 1 study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of TT-00973-MS tablets in patients with solid tumors.
A modified 3+3 design will be used to determine the maximum tolerated dose(MTD) during dose escalation period. Futher expansion period will enroll additional 12\~18 patients at the appropriate dose to futher evaluate the safety and preliminary efficacy of TT-00973-MS.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
The dose levels to be tested in the dose escalation cohorts are 2, 5, 10, 17, 25, 32, 40 and 50mg QD. All the subjects will receive TT-00973-MS tablets QD until disease progression or occurrence of intolerant adverse reactions.
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, China
Anhui Provincial Hospital
Hefei, Anhui, China
Hunan Cancer Hospital
Changsha, Hunan, China
Incidence of Dose Limiting Toxicity (DLT)
To evaluate the incidence of DLT and determine the maximum tolerated dose.
Time frame: At the end Cycle 1(each cycle is 28 days)
Incidence of adverse events and sevious adverse events
To evaluate the safety and tolerability of TT-00973-MS tablets administered orally in patients with advanced solid tumors. NCI CTCAE 5.0 grading system will be used to determine the severity.
Time frame: Adverse events are collected from the patient's first dose of TT-00973-MS until 28 days following the last dose of study drug.
Peak plasma concentration (Cmax)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose on Day 1 single dose; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 28 of Cycle 1
Area under the plasma concentration versus time curve (AUC)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose on Day 1 single dose; pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 28 of Cycle 1
Time to reach maximum plasma concentration (Tmax)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose on Day 1 single dose;pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 28 of Cycle 1
terminal half-life (T1/2)
Time frame: Pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose on Day 1 single dose;pre-dose, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose on Day 28 of Cycle 1
Objective response rate(ORR)
ORR is defined as the rate of CR and PR.
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Time frame: Up to approximately 1 year
Objective response rate(DCR)
DCR is defined as the rate of CR, PR and SD.
Time frame: Up to approximately 1 year
Progression-free survival(PFS)
PFS will be calculated from the date of first dose to the date of documented confirmed relapse/progression or death, whichever occurs first.
Time frame: Until the date of documented confirmed relapse/progression or death, whichever occurs first, assessed up to 1 year.
Duration of response(DOR)
DOR will be calculated as the date of the first documented CR/PR to the date of the first documented confirmed relapse or death, whichever occurs first.
Time frame: Up to approximately 1 year
Overall survival(OS)
Overall survival is defined as the time from first dose to the date of death due to any cause.
Time frame: Up to approximately 1 year