This is a phase I/II study to evaluate the safety and tolerability, DLT(Dose limited toxicity), MTD(Maximum tolerated dose), and RP2D(Recommended phase II dose) of WJB001 capsules in patients with advanced solid tumors, including dose escalation phase, dose expansion phase and cohort expansion phase.The study includes screening, treatment and follow-up periods. In the Dose Escalation phase:Accelerated titration (the first two dose groups) and "BOIN" combination (the subsequent dose group) were used for dose escalation. In the Dose Expansion phase:Based on the previous data, 1 to 2 doses were selected to further evaluate the initial efficacy, safety, tolerability and pharmacokinetic characteristics to confirm RP2D. In the Efficacy Expansion phase:The preliminary plan of Efficacy expansion phase uses the Simon two-stage optimal method to expand 2 to 3 cohorts.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
210
WJB001 Capsules:160mg(or othe dosages),Oral,QD,Days 1-5, 8-12, 15-19 or other dosing frequencies,Every 21 days
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITINGFujian Cancer Hospital
Fuzhou, Fujian, China
RECRUITINGSun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGTumor Hospital Affiliated to Guangxi Medical University
Nanning, Guangxi, China
RECRUITINGUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGHunan Cancer Hospital
Changsha, Hunan, China
RECRUITINGFuxin People's Hospital (Fuxin Women and Children's Medical Center)
Fuxin, Liaoning, China
NOT_YET_RECRUITINGLiaoning Cancer Hospital
Shenyang, Liaoning, China
RECRUITINGShanxi Cancer Hospital
Taiyuan, Shanxi, China
RECRUITINGThe First Affiliated Hospital of Xi 'an Jiaotong University
Xi’an, Shanxi, China
RECRUITING...and 1 more locations
1.Dose limited toxicity (DLT)
incidence of Dose limited toxicity(DLT);
Time frame: 21d
2.Adverse event (AE)
incidence and severity of adverse event (AE), Abnormal changes in laboratory and other tests of clinical significance;
Time frame: 3 years
3.Serious adverse event (SAE)
incidence and severity of Serious adverse event (SAE);
Time frame: 3 years
4.Maximum tolerated dose (MTD)
Maximum tolerated dose (MTD)
Time frame: 2 years
5.Recommended phase II dose (RP2D)
Recommended phase II dose (RP2D)
Time frame: 2 years
6.Objective response rate(ORR)
Efficacy endpoints: Objective response rate(ORR) per RECIST v1.1
Time frame: 3 years
7. Peak time(Tmax)
Pharmacokinetic (PK) parameter : Peak time(Tmax) after a single dose;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
8.Maximum plasma concentration (Cmax)
Pharmacokinetic (PK) parameter : Maximum plasma concentration (Cmax) after a single dose;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
9. (AUC 0-t)
Pharmacokinetic (PK) parameter : Area under blood concentration - time curve(AUC 0-t) after a single dose;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
10. (AUC 0-∞)
Pharmacokinetic (PK) parameter : Area under blood concentration - time curve(AUC 0-∞) after a single dose;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
11.Apparent volume of distribution (Vd/F)
Pharmacokinetic (PK) parameter : Apparent volume of distribution (Vd/F) after a single dose;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
12.Clearance rate (CL/F)
Pharmacokinetic (PK) parameter : Clearance rate (CL/F) after a single dose;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
13. Elimination half-life time ( t1/2)
Pharmacokinetic (PK) parameter : Elimination half-life time ( t1/2)
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
14.Steady state peak concentration(Cmax,ss)
Pharmacokinetic (PK) parameter : Steady state peak concentration(Cmax,ss) after repeated administration;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
15.Steady state valley concentration(Cmin,ss)
Pharmacokinetic (PK) parameter : Steady state valley concentration(Cmin,ss) after repeated administration;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
16.Average steady-state plasma concentration(Cav,ss)
Pharmacokinetic (PK) parameter : Average steady-state plasma concentration(Cav,ss) after repeated administration;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
17. Steady state peak time(Tmax,ss)
Pharmacokinetic (PK) parameter : Steady state peak time(Tmax,ss) after repeated administration;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
18.Steady state Area under blood concentration - time curve(AUC0-t,ss)
Pharmacokinetic (PK) parameter : Steady state Area under blood concentration - time curve(AUC0-t,ss) after repeated administration;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
19.Accumulation Index ( RAC)
Pharmacokinetic (PK) parameter :Accumulation Index ( RAC) after repeated administration;
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
20.Fluctuation coefficient (FD)
Pharmacokinetic (PK) parameter : Fluctuation coefficient (FD)
Time frame: Prior to dose on day 1,5,8,12 and at 0.5,1,1.5, 2,3, 4, 6,8,10 and 24 hours post dose on day 1 and day 12 of Cycle 1
21.Duration of response (DOR)
Efficacy endpoints: Duration of response (DOR) per RECIST v1.1
Time frame: 3 years
22.Disease control rate (DCR)
Efficacy endpoints: Disease control rate (DCR) per RECIST v1.1
Time frame: 3 years
23.Progression-free survival (PFS)
Efficacy endpoints: Progression-free survival (PFS) per RECIST v1.1
Time frame: 2 years
24. Overall survival (OS)
Efficacy endpoints: Overall survival (OS) per RECIST v1.1
Time frame: 3 years
Objective response rate(ORR)
Efficacy endpoints: Objective response rate(ORR) evaluated by Investigator per RECIST v1.1 in Phase I
Time frame: 3 years
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