A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of WJB001 Capsules in Dose Escalation, Dose Expansion, and Efficacy Expansion in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- WJB001
- Conditions
- Advanced Solid Tumors
- Sponsor
- Wigen Biomedicine Technology (Shanghai) Co., Ltd.
- Enrollment
- 210
- Locations
- 10
- Primary Endpoint
- 1.Dose limited toxicity (DLT)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
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 Cohort Expansion phase:The preliminary plan of cohort expansion phase uses the Simon two-stage optimal method to expand 2 to 3 cohorts.
Investigators
Eligibility Criteria
Inclusion Criteria
- •≥ 18 years or older at the time of informed consent；
- •Patient with advanced malignant solid tumors clearly diagnosed pathologically and/or cytologically, who have failed to receive standard treatment, or who currently no have standard treatment, or who are intolerant to standard treatment;
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score ≤1;
- •Life expectancy ≥ 12 weeks;
- •Adequate hematologic and organ function；
- •All acute toxic effects from previous antineoplastic therapy or surgery ；
- •Fertile women must confirm a negative blood pregnancy test within 7 days prior to the first administration of study drug;and they required to use adequate and effective contraceptive measures throughout the treatment period and within 3 months after the end of treatment;Fertile women in this protocol were defined as sexually mature women: 1) not undergoing hysterectomy or bilateral oophorectomy; 2) 24 months without a continuous period of spontaneous menopause (i.e., having had a period at any time in the previous 24 consecutive months; Amenorrhea after cancer treatment does not exclude fertility). Male participants with a sexual partner who was a woman of reproductive age had to agree to use an effective contraceptive method while using the study drug and for 3 months after the last dose；
- •Specific inclusion criteria：
- •At least one measurable tumor lesion that meets the definition of RECIST v1.1, with no history of biopsy two weeks before screening(applicable to all stages);
- •Subjects with CCNE1 overexpression (H score \> 50) or amplification (DNA copy number \> 7)confirmed by central laboratory (applicable to the dose expansion stage and efficacy expansion stage);
Exclusion Criteria
- Not provided
Arms & Interventions
WJB001 capsules
Once a day (QD).
Intervention: WJB001
Outcomes
Primary Outcomes
1.Dose limited toxicity (DLT)
Time Frame: 3 years
incidence of Dose limited toxicity(DLT);
2.Adverse event (AE)
Time Frame: 3 years
incidence and severity of adverse event (AE), Abnormal changes in laboratory and other tests of clinical significance;
3.Serious adverse event (SAE)
Time Frame: 3 years
incidence and severity of Serious adverse event (SAE);
4.Maximum tolerated dose (MTD)
Time Frame: 2 years
Maximum tolerated dose (MTD)
5.Recommended phase II dose (RP2D)
Time Frame: 2 years
Recommended phase II dose (RP2D)
6.Objective response rate(ORR)
Time Frame: 3 years
Efficacy endpoints: Objective response rate(ORR) per RECIST v1.1
Secondary Outcomes
- 7. Peak time(Tmax)(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)(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)(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-∞)(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)(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)(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)(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)(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)(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)(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)(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)(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)(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)(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)(3 years)
- 22.Disease control rate (DCR)(3 years)
- 23.Progression-free survival (PFS)(2 years)
- 24. Overall survival (OS)(3 years)