Advanced Solid Tumor
Conditions
Brief summary
This is a phase I/II study to preliminarily explore of the safety, tolerability, pharmacokinetics, and efficacy of WJB001 combination therapy, consisting of three stages: Dose escalation (Phase Ia), dose extension (Phase Ib), and efficacy extension (Phase II). The preliminary plan includes seven combination therapy regimens, namely Arm A: WJB001+taxanes (A1: WJB001+paclitaxel, A2: WJB001+albumin paclitaxel); Arm B: WJB001+platinum (B1: WJB001+carboplatin, B2: WJB001+nedaplatin); Arm C: WJB001+paclitaxel+carboplatin; Arm D: WJB001+PARP inhibitor; Arm E: WJB001+VEGF inhibitor; Arm F:WJB001+JS207/JS001（F1：WJB001+JS207，F2：WJB001+JS001）；Arm G：WJB001+JS207/JS001+paclitaxel+carboplatin（G1: WJB001+JS207 +paclitaxel+carboplatin；G2：WJB001+JS001+paclitaxel+carboplatin）.
Detailed description
The study is a multicenter,phase I/II clinical trial, divided into three parts: In the Dose Escalation phase(Phase Ia): BOIN design were used to search the Maximum tolerated dose (MTD), allowing to increase or decrease the dose of one or separate drugs in the combination for dosage exploration.Recruitment by Arm, estimate 5 7 cohort, with several dose levels planned for each cohort: In the Arm A/B/C combination therapy, chemotherapy (taxanes, platinum) is administered for a maximum of 6 cycles. After chemotherapy, WJB001 monotherapy is used to maintain treatment until the subject's disease progresses or withdrawl; In the Arm D combination therapy, the PARP inhibitor, such as Niraparib, is administered every 21 days in a cycle until the subject's disease progresses or withdrawl. In the Arm E combination therapy, as an example, Bevacizumab can be treated for a maximum of 22 cycles or unacceptable side effects occur (whichever occurs first), and then Bevacizumab treatment is terminated and maintained with WJB001 monotherapy until the subject's disease progression or withdrawal In the Arm F1 combination therapy, JS207 is treated for 2 years or with unacceptable side effects (whichever occurs first) before disease progression occurs, and then JS207 treatment is terminated. Arm F2/G2: JS001 Treat until unacceptable side effects occur (whichever occurs first) before disease progression occurs.Upon termination of JS207/JS001 treatment, maintenance therapy with WJB001 monotherapy will be administered at a dose of 160 mg or the current dose (as determined by the investigator), until disease progression or withdrawal. In the Arm G combination therapy, chemotherapy (paclitaxel, platinum) is administered for up to 6 cycles,WJB001+JS207/JS001 is maintained at the RP2D dose of the two drugs explored in Arm F or the current dose (determined by Investigator). In the Dose Expansion phase(Phase Ib): 1 to 2 dose levels for each group will be selected the sponsor and the SMC based on the previous data, to further evaluate the preliminary efficacy, safety, tolerability and pharmacokinetic characteristics of the combination therapy in the target population, and confirm the RP2D dose of different combination regimens. Efficacy Expansion Stage(Phase II): At the RP2D regimen determined in the Phase IB study, to explore the efficacy, safety, tolerability and pharmacokinetic characteristics of WJB001 combination therapy in the target population. And 2 to 3 cohorts is preliminarily planned for expansion and the "Simon Two-Stage" design is adopted.
Interventions
DRUGWJB001 Capsules+Paclitaxel/Paclitaxel-albumin
WJB001 Capsules:120mg(or 160mg,80mg,40mg,or 100mg,60mg),Oral,QD,Days 1-5, 8-12, 15-19 or other dosing frequencies (e.g., days 1-4, 8-11, 15-18),Every 21 days; Paclitaxel:80 mg/m2(or 60 mg/m2 ,50 mg/m2), Day 1, day 8, day 15, intravenous infusion, 21 days 1 cycle, up to 6 cycles; Paclitaxel-albumin:260mg/m2(220mg/m2,180mg/m2),On day 1, intravenous infusion, 21 days 1 cycle, up to 6 cycles
DRUGWJB001 Capsules+carboplatin/Nedaplatin
WJB001 Capsules:80mg(or160mg, 120mg,40mg,or 100mg,60mg),Oral,QD,Days 1-5, 8-12, 15-19 or other dosing frequencies (e.g., days 1-4, 8-11, 15-18),Every 21 days; Carboplatin:AUC 5 mg/ml\*min(or 4mg/ml\*min,3mg/ml\*min), Day 1, day 8, day 15, intravenous infusion, 21 days 1 cycle, up to 6 cycles; Nedaplatin:100mg(80mg/m2 ,60mg/m2), Day 1, intravenous infusion, 21 days 1 cycle, up to 6 cycles;
DRUGWJB001 Capsules+Paclitaxel+carboplatin
WJB001 Capsules:40mg(or 160mg, 120 mg,80mg,60mg,or 100mg,60mg),Oral,QD,Days 1-5, 8-12, 15-19 or other dosing frequencies (e.g., days 1-4, 8-11, 15-18),Every 21 days; Paclitaxel:60 mg/m2, Day 1, day 8, day 15, intravenous infusion, 21 days 1 cycle, up to 6 cycles; Carboplatin:AUC 2mg/ml\*min, Day 1, day 8, day 15, intravenous infusion, 21 days 1 cycle, up to 6 cycles;
DRUGWJB001 Capsules+Niraparib
WJB001 Capsules:120mg(or 160mg,80mg,40mg,or 100mg,60mg),Oral,QD,Days 1-5, 8-12, 15-19 or other dosing frequencies (e.g., days 1-4, 8-11, 15-18),Every 21 days; Niraparib:Niraparib:300mg(or 200mg,100mg),Oral,QD,Every 21 days;
DRUGWJB001 Capsules+Bevacizumab
WJB001 Capsules:120mg(or 160mg,80mg,40mg,or 100mg,60mg),Oral,QD,Days 1-5, 8-12, 15-19 or other dosing frequencies (e.g., days 1-4, 8-11, 15-18),Every 21 days; Bevacizumab:15mg/kg(or 7.5mg/kg),intravenous infusion, 21 days 1 cycle, up to 22 cycles or unacceptable side effects；
DRUGWJB001 Capsules+JS207/JS001
WJB001 Capsules:120mg/160mg ( (or referring to previously conducted cohorts or other clinical studies ),Oral,QD,Days 1-5, 8-12, 15-19 or other dosing frequencies (e.g., days 1-4, 8-11, 15-18),Every 21 days; JS207:10mg/kg(or lower dosage),intravenous infusion, 21 days 1 cycle, up to 2 years or unacceptable side effects； Toripalimab:240 mg,intravenous infusion,21 days 1 cycle, up to desease progression or unacceptable side effects；
DRUGWJB001 Capsules+Paclitaxel+carboplatin+JS207/Toripalimab
WJB001 Capsules:40mg (or referring to previously conducted cohorts or other clinical studies ),Oral,QD,Days 1-5, 8-12, 15-19 or other dosing frequencies (e.g., days 1-4, 8-11, 15-18),Every 21 days; JS207:10mg/kg(or lower dosage),intravenous infusion, 21 days 1 cycle, up to 2 years or unacceptable side effects Toripalimab:240 mg,intravenous infusion,21 days 1 cycle, up to desease progression or unacceptable side effects Paclitaxel:60 mg/m2, Day 1, day 8, day 15, intravenous infusion, 21 days 1 cycle, up to 6 cycles; Carboplatin:AUC 2mg/ml\*min, Day 1, day 8, day 15, intravenous infusion, 21 days 1 cycle, up to 6 cycles;
Sponsors
Wigen Biomedicine Technology (Shanghai) Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the following inclusion criteria: 1. Participants voluntarily participate in this study with full informed consent and sign an informed consent form（ICF）. 2. Age ≥ 18 years old, No gender limitation,witih BMI (Body Mass Index) ≥ 18.5. 3. Patients diagnosed with Advanced solid tumors confirmed by pathology and/or cytology, must meet the following criteria: 1. For the detection of biomarkers such as CCNE1,tumor tissue samples must be provided from the patient 2. CCNE1 overexpression confirmed by central laboratory immunohistochemistry (IHC) in tumor tissue 3. Have failed or are intolerant to standard treatments or have no available standard treatments options(Applicable to Dose escalation phase) 4. For patients with platinum-sensitive or platinum-resistant recurrent advanced high-grade serous ovarian cancer(HGSOC), fallopian tube cancer, or peritoneal cancer, as well as advanced uterine serous carcinoma (USC) 4. There is at least one Target lesion that meets the definition of RECIST v1.1 criteria, and the selected target lesion has not received biopsy in the past two weeks. 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 6. Expected survival time ≥12 week. 7. Having Adequate hematologic and organ function, the following laboratory tests should be conducted within 7 days prior to the first administration of the investigational drug (No blood transfusion, without receiving hematopoietic stimulating factors or human albumin preparations within 14 days prior to the examination): 1. Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L 2. Hemoglobin\>90 g/L 3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN)(for patients with liver metastases ，AST and ALT≤ 5.0× ULN) 4. Total bilirubin (TBIL) ≤ 1.5 × ULN(for patients enrolled in Arm A，Arm C and Arm G , TBIL≤ 1.2.5× ULN；patients with Gilbert's Syndrome，TBIL≤3×ULN and Direct bilirubin≤ 1.5 × ULN) 5. Serum creatinine(Cr) ≤1.5×ULN or Creatinine clearance (Ccr, calculated using Cockcroft-Gault formula) ≥45 mL/min (for patients enrolled in Arm B,Arm C and Arm G, Creatinine clearance ≥60 mL/min) 8. All acute toxic reactions due to prior antitumor therapy or surgery have resolved to baseline level or grade ≤ 1 defined by NCI CTCAE V5.0 (except alopecia or pigmentation). 9. The effective contraceptive methods must be used.
Exclusion criteria
Participants must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limited toxicity (DLT) | 21day | Incidence of Dose limited toxicity(DLT) |
| Adverse event (AE) | 3 years | Incidence and severity of adverse event (AE), Abnormal changes in laboratory and other tests of clinical significance |
| Serious adverse event (SAE) | 3 years | Incidence and severity of Serious adverse event (SAE) |
| Maximum tolerated dose (MTD) | 2 years | Maximum tolerated dose (MTD) |
| Recommended phase II dose (RP2D) | 2 years | Recommended phase II dose (RP2D) |
| Objective response rate(ORR) | 3 years | Objective response rate(ORR) evaluated by Investigator per RECIST v1.1 in Phase II |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak time(Tmax) | 4 Months | Pharmacokinetic (PK) parameter : Peak time(Tmax) after a single dose of WJB001/JS207； |
| Maximum plasma concentration (Cmax) | 4 Months | Maximum plasma concentration (Cmax) after a single dose of WJB001/JS207; |
| (AUC 0-t) | 4 Months | Area under blood concentration - time curve(AUC 0-t) after a single dose of WJB001/JS207; |
| (AUC 0-∞) | 4 Months | Area under blood concentration - time curve(AUC 0-∞) after a single dose of WJB001/JS207; |
| Apparent volume of distribution (Vd/F) | 4 Months | Apparent volume of distribution (Vd/F) after a single dose of WJB001/JS207; |
| Clearance rate (CL/F) | 4 Months | Clearance rate (CL/F) after a single dose of WJB001/JS207; |
| Elimination half-life time ( t1/2) | 4 Months | Elimination half-life time ( t1/2) after a single dose of WJB001/JS207; |
| Steady state peak concentration(Cmax,ss) | 4 Months | Steady state peak concentration(Cmax,ss) after multiple administration for WJB001/JS207; |
| Steady state valley concentration(Cmin,ss) | 4 Months | Steady state valley concentration(Cmin,ss) after multiple administration for WJB001/JS207; |
| Average steady-state plasma concentration(Cav,ss) | 4 Months | Average steady-state plasma concentration(Cav,ss) after multiple administration for WJB001/JS207; |
| Steady state peak time(Tmax,ss) | 4 Months | Steady state peak time(Tmax,ss) after multiple administration for WJB001/JS207; |
| Steady state Area under blood concentration - time curve(AUC0-t,ss) | 4 Months | Steady state Area under blood concentration - time curve(AUC0-t,ss) after multiple administration for WJB001/JS207; |
| Accumulation Index ( RAC) | 4 Months | Accumulation Index ( RAC) after multiple administration for WJB001/JS207; |
| Anti-drug antibodies (ADA) | 2 years | Incidence and titer of anti-drug antibodies (ADA) for JS207； |
| Neutralizing Antibody (NAb) | 2 years | Incidence of Antibody (NAb) for JS207 |
| Objective response rate(ORR) | 3 years | Objective response rate(ORR) evaluated by Investigator per RECIST v1.1 in Phase I |
| Duration of response (DOR) | 3 years | Efficacy endpoints : Duration of response (DOR) evaluated by Investigator per RECIST v1.1 |
| Disease control rate (DCR) | 3 years | Efficacy endpoints: Disease control rate (DCR) evaluated by Investigator per RECIST v1.1； |
| Time of Disease Progression (TTP) | 3 years | Time of Disease Progression (TTP) evaluated by Investigator per RECIST v1.1 |
| Progression-free survival (PFS) | 3 years | Progression-free survival (PFS) evaluated by Investigator per RECIST v1.1 |
| Overall survival (OS) | 3 years | Overall survival (OS) evaluated by Investigator per RECIST v1.1 |
| CCNE1 | 3 years | The correlation between CCNE1 overexpression or amplification and therapeutic efficacy |
Countries
China
Contacts
CONTACTYirong Zhao, Master
Outcome results
None listed