This is a phase I study to Investigate the safety and tolerability, DLT(Dose limited toxicity), MTD(Maximum tolerated dose), and RP2D(Recommended phase II dose) of WJ01075 tablets in patients with advanced malignant solid tumors, including phase Ia (dose escalation phase) and Phase Ib (dose expansion phase,cohort expansion phase).The study includes screening, treatment and follow-up periods. In phase Ia, accelerated titration (the first two dose groups) and "3 + 3" combination (the subsequent dose group) were used for dose escalation. In phase Ib, specific dose groups will be selected for dose expansion according to PK(Pharmacokinetics) and safety data of different dose groups in dose escalation phase.It is planned that SMC(Safety Monitoring Committee) will select one or more dose groups based on previous data for cohort expansion studies to further determine RP2D, safety tolerability and initial efficacy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Phase Ia: Dose Escalation Accelerated titration (the first two dose groups) and "3 + 3" combination (the subsequent dose group) were used for dose escalation. Phase Ib: Dose Expansion and Cohort Expansion The actual dose, dosing schedule (including combination) and indication selection will be evaluated based on the results of existing trials.
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, China
Dose limited toxicity (DLT)
incidence and severity of Dose limited toxicity(DLT);
Time frame: 3 years
Adverse event (AE)
incidence and severity of adverse event (AE), Abnormal changes in laboratory and other tests of clinical significance;
Time frame: 3 years
Serious adverse event (SAE)
incidence and severity of Serious adverse event (SAE);
Time frame: 3 years
Maximum tolerated dose (MTD)
Maximum tolerated dose (MTD)
Time frame: 2 years
Recommended phase II dose (RP2D)
Recommended phase II dose (RP2D)
Time frame: 2 years
Objective response rate(ORR)
Efficacy endpoints: Objective response rate(ORR) per RECIST v1.1
Time frame: 2 years
Duration of response (DOR)
Efficacy endpoints: Duration of response (DOR) per RECIST v1.1
Time frame: 2 years
Disease control rate (DCR)
Efficacy endpoints: Disease control rate (DCR) per RECIST v1.1
Time frame: 2 years
Time to response(TTR)
Efficacy endpoints: Time to response(TTR) per RECIST v1.1
Time frame: 2 years
Progression-free survival (PFS)
Efficacy endpoints: Progression-free survival (PFS) per RECIST v1.1
Time frame: 2 years
Overall survival (OS)
Efficacy endpoints: Overall survival (OS) per RECIST v1.1
Time frame: 2 years
Peak time(Tmax)
Pharmacokinetic (PK) parameter : Peak time(Tmax) after a single dose;
Time frame: 2 years
Maximum plasma concentration (Cmax)
Pharmacokinetic (PK) parameter : Maximum plasma concentration (Cmax) after a single dose;
Time frame: 2 years
Clearance rate (CL/F)
Pharmacokinetic (PK) parameter : Clearance rate (CL/F) after a single dose;
Time frame: 2 years
Apparent volume of distribution (Vd/F)
Pharmacokinetic (PK) parameter : Apparent volume of distribution (Vd/F) after a single dose;
Time frame: 2 years
Area under blood concentration - time curve (AUC)
Pharmacokinetic (PK) parameter : Area under blood concentration - time curve (AUC) after a single dose;
Time frame: 2 years
Elimination rate constant (λz)
Pharmacokinetic (PK) parameter : Elimination rate constant (λz) after a single dose;
Time frame: 2 years
Elimination half-life time ( t1/2) and other parameters
Pharmacokinetic (PK) parameter : Elimination half-life time ( t1/2) and other parameters after a single dose;
Time frame: 2 years
Steady state valley concentration(Cssmin)
Pharmacokinetic (PK) parameter : Steady state valley concentration(Cssmin) after repeated administration;
Time frame: 2 years
Steady state peak concentration(Cssmax)
Pharmacokinetic (PK) parameter : Steady state peak concentration(Cssmax) after repeated administration;
Time frame: 2 years
Average steady-state plasma concentration(Css-av)
Pharmacokinetic (PK) parameter : Average steady-state plasma concentration(Css-av) after repeated administration;
Time frame: 2 years
Elimination half-life time ( t1/2)
Pharmacokinetic (PK) parameter : Elimination half-life time ( t1/2) after repeated administration;
Time frame: 2 years
Steady state Area under blood concentration - time curve(AUCss)
Pharmacokinetic (PK) parameter : Steady state Area under blood concentration - time curve(AUCss) after repeated administration;
Time frame: 2 years
Fluctuation coefficient (DF)
Pharmacokinetic (PK) parameter : Fluctuation coefficient (DF) after repeated administration;
Time frame: 2 years
Steady-state distribution volume(Vss )
Pharmacokinetic (PK) parameter : Steady-state distribution volume(Vss ) after repeated administration;
Time frame: 2 years
Accumulation coefficient (AR) and other parameters
Pharmacokinetic (PK) parameter : Accumulation coefficient (AR) and other parameters after repeated administration;
Time frame: 2 years
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