A Phase I/II Study of WJB001 Combination Therapy on Safety and Efficacy for Advanced Solid Tumors

A Dose-escalation, Dose-expansion and Efficacy Extension Phase I/II Study to Evaluate the Safety and Tolerability, Pharmacokinetics, and Preliminary Efficacy of WJB001 Combination Therapy in Patients With Advanced Solid Tumors

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）.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: WJB001 Capsules+Paclitaxel/Paclitaxel-albumin; Drug: WJB001 Capsules+carboplatin/Nedaplatin; Drug: WJB001 Capsules+Paclitaxel+carboplatin; Drug: WJB001 Capsules+Niraparib; Drug: WJB001 Capsules+Bevacizumab; Drug: WJB001 Capsules+JS207/JS001; Drug: WJB001 Capsules+Paclitaxel+carboplatin+JS207/Toripalimab

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.

• Study Type: Interventional
• Enrollment (Estimated): 86
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yirong Zhao, Master; Phone Number: 15221069447; Email: yrzhao@wigenbio.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Sciences
      • Contact: Lingying Wu, Professor; Phone Number: 13910865483; Email: wulingying@csco.org.cn
      • Principal Investigator: Lingying Wu, Professor
      • Sub-Investigator: Ning Li, Doctor
  • Fujian
    • Fuzhou, Fujian, China, 350000
      • Recruiting
      • Fujian Cancer Hospital
      • Contact: An Lin, Professor; Phone Number: 13805015679; Email: linan640906@163.com
      • Principal Investigator: An Lin, Professor
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun yat-sen University Cancer Center
      • Contact: Jundong Li, Professor; Phone Number: 13602859866; Email: lijd@sysucc.org.cn
      • Principal Investigator: Jundong Li, Professor
  • Guangxi
    • Nanning, Guangxi, China, 530000
      • Recruiting
      • Tumor Hospital Affiliated to Guangxi Medical University
      • Contact: Jieqing Zhang, Professor; Phone Number: 15278015900; Email: 1583825050@qq.com
      • Principal Investigator: Jieqing Zhang, Professor
  • Gunagdong
    • Guangzhou, Gunagdong, China, 510000
      • Recruiting
      • Sun Yat-sen Hospital, Sun Yat-sen University
      • Contact: Qunxian Rao, Professor; Phone Number: 13902250700; Email: badger777@163.com
      • Principal Investigator: Qunxian Rao, Professor
  • Hubei
    • Wuhan, Hubei, China, 430023
      • Recruiting
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Guilin Li, Professor; Phone Number: 13307187507; Email: lgl6714@163.com
      • Principal Investigator: Guilin Li, Professor
  • Hunan
    • Changsha, Hunan, China, 410000
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Jie Tang, Professor; Phone Number: 15274836636; Email: tangjie@hnca.org.cn
      • Principal Investigator: Jie Tang, Professor
  • Liaoning
    • Shenyang, Liaoning, China, 110000
      • Recruiting
      • Liaoning Cancer Hospital
      • Contact: Danbo Wang, Professor; Phone Number: 18940251157; Email: danbo_wang@126.com
      • Principal Investigator: Danbo Wang, Professor
    • Shenyang, Liaoning, China, 110000
      • Recruiting
      • The First Affiliated Hospital of China Medical University
      • Contact: Funan Liu, Professor; Phone Number: 13609877906; Email: lfn_clinical@126.com
      • Principal Investigator: Funan Liu, Professor
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Xuejun Chen, Professor; Phone Number: 13757119632; Email: startchen@zju.edu.cn
      • Principal Investigator: startchen@zju.edu.cn Chen, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 exclusion criteria:

1. General condition.

   1. Pregnant or lactating women
   2. Any known allergies to or contraindications to components of the study drug
   3. History of substance abuse
   4. History of alcohol abuse or consumption of more than 28 units of alcohol per week (1 unit =285 ml beer or 25 ml spirits (40%v/v) or 100 ml wine)

2. Previous or current treatment:

   1. Previous or current treatment with Wee1 inhibitors,as well as CDK2, PKMYT1, PARG, and ATR inhibitors
   2. Having received cytotoxic chemotherapy drugs, traditional Chinese medicine treatment indicated for anti-tumor purposes, or other anti-tumor drugs (such as small-molecule targeted therapy, etc.) within 14 days before the first administration of the study treatment; or having received investigational drugs, macromolecular drugs with anti-tumor effects (such as monoclonal antibodies, antibody-drug conjugates, or bispecific antibodies, etc.) within 28 days before the first administration of the study treatment; or requiring continued treatment with these drugs during the study period
   3. Currently using moderate or strong CYP3A inhibitors or inducers, or other products (such as grapefruit juice), or P-gp inhibitors or inducers, and the drug discontinuation time is less than 5 half-lives of the drug or 14 days (whichever is shorter) before the first administration of WJB001
   4. Known with having a organ transplant or stem cell transplant; Having major surgery or severe trauma (excluding needle biopsy for sample collection) within 4 weeks prior to the first administration of study drug;Minor surgery within 7 days before the first dose, excluding the placement of vascular infusion devices;
   5. Radiation therapy was administered within 21 days prior to the first administration of study drug, except for cases where radiation therapy is less than or equal to 5% of bone marrow volume, and regardless of when radiation therapy was received, the patients can be included in the study;Any local treatment for cancer such as thoracoabdominal perfusion therapy was received within 14 days before the first administration
   6. Poorly controlled pleural effusion, ascites, or pericardial effusion (poor control is defined as requiring puncture and drainage during the screening period or having undergone drainage within 3 months before the first dose of medication)
   7. Patients with a history of drug-related adverse events leading to permanent discontinuation during previous treatment with anti-PD-(L)1 antibodies or analogs or other therapies targeting the same pathway; (applicable only to Arm F and/or Arm G)
   8. Patients with a history of drug-related adverse events leading to permanent discontinuation during previous treatment with anti-VEGF monoclonal antibodies or analogs or other therapies targeting the same pathway; (applicable only to Arm E, F, and/or Arm G)
   9. Having received any live vaccine or live-attenuated vaccine within 28 days prior to the first dose, or anticipated to require such vaccination during the study period
   10. Having received antiplatelet therapy within 10 days prior to the first dose (aspirin ≤325 mg/day is allowed) or anticoagulant therapy for treatment purposes (prophylactic anticoagulation is allowed);
   11. Patients with primary platinum-refractory disease (defined as disease progression during the first platinum-containing regimen or within 4 weeks)

3. Past medical history, present medical history and abnormal laboratory indicators:

   1. Having active gastrointestinal abnormalities including, but not limited to, inability to take oral medication, need for intravenous nutritional support, peptic ulcer, chronic diarrhea (e.g., Crohn's disease, irritable bowel syndrome), or vomiting or other factors that the investigator deems may significantly affect absorption, metabolism, or excretion of the drug (such as a small intestinal stoma, etc.)
   2. There was a history of severe eye diseases in the past (excluding permanent blindness caused by the disease), and it has not been recovered Grade ≤1 at present
   3. Patients with active brain metastases (except if they have central nervous system (CNS) metastases confined to the supratentorial or cerebellar region, having received adequately treatment (surgery or radiotherapy), having maintained radiological stability for at least 4 weeks, and do not require corticosteroids for symptom control)
   4. Patients currently have suffered carcinomatous meningitis, spinal cord compression, and hepatic encephalopathy, etc
   5. Severe or poorly controlled hypertension, including a history of hypertensive crisis or hypertensive encephalopathy; having Adjustment of antihypertensive medication due to poor blood pressure control within 2 weeks before the first dose;Systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg during the screening period
   6. Having any of the following cardiac criteria: cardiomyopathy, ischemic heart disease, valvular disease, hypertensive heart disease, heart failure, presyncope or syncope of unexplained or cardiovascular origin, ventricular tachycardia, ventricular fibrillation, or cardiac arrest. At rest, the average corrected QT interval (QTc, calculated using Fridericia's correction formula) obtained from three electrocardiogram (ECG) examinations is >450 ms for males or >470 ms for females (repeated three times). Various clinically significant arrhythmias, conduction abnormalities, and resting ECG morphological abnormalities, such as complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, PR interval >250 ms. Echocardiography shows that the left ventricular ejection fraction (LVEF) < 50%. Various factors that may increase the risk of QTc prolongation or arrhythmia events, such as heart failure, hypokalemia, a history of congenital long QT syndrome or torsades de pointes (TdP), a family history of long QT syndrome in a direct relative or sudden unexplained death of a direct relative before the age of 40, and currently using any drug known to prolong the QT interval
   7. Having clinically significant bleeding symptoms or obvious bleeding tendency within 4 weeks before the first dose, such as gastrointestinal bleeding, gastric ulcer bleeding, obvious gross hematuria, or suffering from vasculitis,etc; Or have evidence of major coagulation disorders within 6 months before the first administration of the drug, such as events like deep vein thrombosis of the lower extremities, myocardial infarction, etc
   8. Having active HBV and HCV infection: if HBsAg is positive or/and anti-HBC is positive, blood HBV DNA need to be tested to confirm that it is higher than the limit of quantitative detection; If anti-HCV is positive, HCV RNA need to be tested to confirm that the HCV viral copy number exceeds the quantitative detection limit
   9. known history of human immunodeficiency virus infection or having a positive result for serum anti-HIV test
   10. History of other primary solid tumor(except for the radically cured solid tumor ,which is inactive and has a very low risk of recurrence for ≥5 years before screening）; Non-melanoma skin cancer or lentigo maligna that has been adequately treated andshows no evidence of disease recurrence; Carcinoma in situ, such as cervical carcinoma in situ, that has been adequately treated and shows no evidence of disease recurrence)
   11. Severe active infectious diseases or other diseases that seriously affect the safety of the first medication occurred during the screening period
   12. Within 2 years prior to the first use of medication, there are active autoimmune diseases that require systemic treatment (such as corticosteroids or immunosuppressive drugs), including but not limited to: systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, vasculitis, etc. However, screening is allowed for hypothyroidism, adrenal or pituitary dysfunction, type I diabetes that can be controlled only by hormone replacement therapy, psoriasis or vitiligo that does not need systematic treatment, and childhood asthma/allergy that has been cured
   13. History of interstitial lung disease or history of non infectious pneumonia and treatment with corticosteroids, or screening imaging showing evidence of active pneumonia
   14. TP53 showed wild-type phenotype (wild type of TP53 detected by genetic testing or p53 protein expression detected negative by immunohistochemistry)
   15. The investigator deems that the patient has other factors that may affect the research results and interfere with their participation in the entire research process. These factors include, but are not limited to, past or current physical conditions (such as mental disorders, optic nerve atrophy, excessive low body weight, severe hydronephrosis, or thyroid dysfunction), treatments, or abnormal laboratory test results. The subject is unwilling to abide by various procedures, restrictions, and requirements of the study, is unable to cooperate or undergo MRI or CT scans, or has psychological or social conditions that may interfere with their participation in the study or have an impact on the evaluation of the study results, etc

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: WJB001 capsules with Taxanes; If needed, additional descriptive information (including which interventions are administered in each arm) to differentiate each arm from other arms in the clinical trial. Phase Ia: Participants with advanced solid tumor will receive WJB001 capsules at escalating dose levels after a maximum of 6 cycles of Paclitaxel/Paclitaxel-albumin. Phase Ib/II: Participants with High-grade serous ovarian cancer（HGSOC）,fallopian tube cancer,peritoneal cancer ,or Uterine Serous Carcinoma(USC) will receive WJB001 capsules at escalating dose levels after a maximum of 6 cycles of Paclitaxel/Paclitaxel-albumin Paclitaxel/Paclitaxel-albumin.	Drug: WJB001 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; Other Names: Wee1 inhibitor+ Taxol/Abraxane
Experimental: WJB001 capsules with Platinum; If needed, additional descriptive information (including which interventions are administered in each arm) to differentiate each arm from other arms in the clinical trial. Phase Ia: Participants with advanced solid tumor will receive WJB001 capsules at escalating dose levels after a maximum of 6 cycles of carboplatin/Nedaplatin. Phase Ib/II: Participants with High-grade serous ovarian cancer（HGSOC）,fallopian tube cancer,peritoneal cancer ,or Uterine Serous Carcinoma(USC) will receive WJB001 capsules at escalating dose levels after a maximum of 6 cycles of carboplatin/Nedaplatin.	Drug: WJB001 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; Other Names: Wee1 inhibitor+ PARAPLATIN/Aqupla
Experimental: WJB001 capsules with paclitaxel+carboplatin; If needed, additional descriptive information (including which interventions are administered in each arm) to differentiate each arm from other arms in the clinical trial. Phase Ia: Participants with advanced solid tumor will receive WJB001 capsules at escalating dose levels after a maximum of 6 cycles of Paclitaxel+carboplatin. Phase Ib/II: Participants with High-grade serous ovarian cancer（HGSOC）,fallopian tube cancer,peritoneal cancer ,or Uterine Serous Carcinoma(USC) will receive WJB001 capsules at escalating dose levels iafter a maximum of 6 cycles of Paclitaxel+carboplatin.	Drug: WJB001 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; Other Names: Wee1 inhibitor+ PARAPLATIN+Taxol
Experimental: WJB001 capsules with PARPi; If needed, additional descriptive information (including which interventions are administered in each arm) to differentiate each arm from other arms in the clinical trial. Phase Ia: Participants with advanced solid tumor will receive WJB001 capsules at escalating dose levels in combination with PAPPi. Phase Ib/II: Participants with High-grade serous ovarian cancer,fallopian tube cancer（HGSOC）,peritoneal cancer ,or Uterine Serous Carcinoma(USC) will receive WJB001 capsules at escalating dose levels in combination with PAPPi.	Drug: WJB001 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; Other Names: Wee1 inhibitor+ Zejula
Experimental: WJB001 capsules with VEGFi; If needed, additional descriptive information (including which interventions are administered in each arm) to differentiate each arm from other arms in the clinical trial. Phase Ia: Participants with advanced solid tumor will receive WJB001 capsules at escalating dose levels in combination with VEGFi. Phase Ib/II: Participants with High-grade serous ovarian cancer（HGSOC）,fallopian tube cancer,peritoneal cancer ,or Uterine Serous Carcinoma(USC) will receive WJB001 capsules at escalating dose levels in combination with VEGFi.	Drug: WJB001 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； Other Names: Wee1 inhibitor+ Avastin
Experimental: WJB001 capsules with Anti-PD-1 and VEGF bispecific antibodies/ Anti-PD-1 antibodies; If needed, additional descriptive information (including which interventions are administered in each arm) to differentiate each arm from other arms in the clinical trial. Phase Ia: Participants with advanced solid tumor will receive WJB001 capsules at escalating dose levels in combination with Anti-PD-1 and VEGF bispecific antibodies/ Anti-PD-1 antibodies . Phase Ib/II: Participants with High-grade serous ovarian cancer（HGSOC）,fallopian tube cancer,peritoneal cancer ,or Uterine Serous Carcinoma(USC) will receive WJB001 capsules at escalating dose levels in combination with Anti-PD-1 and VEGF bispecific antibodies/ Anti-PD-1 antibodies.	Drug: WJB001 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； Other Names: Wee1 inhibitor+JS207/Toripalimab
Experimental: WJB001 capsules with paclitaxel and carboplatin, together with Anti-PD-1 and VEGF bispecific antibo; If needed, additional descriptive information (including which interventions are administered in each arm) to differentiate each arm from other arms in the clinical trial. Phase Ia:Participants with advanced solid tumor will receive WJB001 capsules in combination with paclitaxel and carboplatin, together with Anti-PD-1 and VEGF bispecific antibodies/ Anti-PD-1 antibodies . Phase Ib and II:Participants with High-grade serous ovarian cancer,fallopian tube cancer,peritoneal cancer ,or Uterine Serous Carcinoma will receive WJB001 capsules in combination with paclitaxel and carboplatin, together with Anti-PD-1 and VEGF bispecific antibodies/ Anti-PD-1 antibodies .	Drug: WJB001 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;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	Maximum tolerated dose (MTD)	2 years
Recommended phase II dose (RP2D)	Recommended phase II dose (RP2D)	2 years
Adverse event (AE)	Incidence and severity of adverse event (AE), Abnormal changes in laboratory and other tests of clinical significance	3 years
Serious adverse event (SAE)	Incidence and severity of Serious adverse event (SAE)	3 years
Dose limited toxicity (DLT)	Incidence of Dose limited toxicity(DLT)	21day
Objective response rate(ORR)	Objective response rate(ORR) evaluated by Investigator per RECIST v1.1 in Phase II	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak time(Tmax)	Pharmacokinetic (PK) parameter : Peak time(Tmax) after a single dose of WJB001/JS207；	4 Months
Maximum plasma concentration (Cmax)	Maximum plasma concentration (Cmax) after a single dose of WJB001/JS207;	4 Months
(AUC 0-t)	Area under blood concentration - time curve(AUC 0-t) after a single dose of WJB001/JS207;	4 Months
(AUC 0-∞)	Area under blood concentration - time curve(AUC 0-∞) after a single dose of WJB001/JS207;	4 Months
Apparent volume of distribution (Vd/F)	Apparent volume of distribution (Vd/F) after a single dose of WJB001/JS207;	4 Months
Clearance rate (CL/F)	Clearance rate (CL/F) after a single dose of WJB001/JS207;	4 Months
Elimination half-life time ( t1/2)	Elimination half-life time ( t1/2) after a single dose of WJB001/JS207;	4 Months
Steady state peak concentration(Cmax,ss)	Steady state peak concentration(Cmax,ss) after multiple administration for WJB001/JS207;	4 Months
Steady state valley concentration(Cmin,ss)	Steady state valley concentration(Cmin,ss) after multiple administration for WJB001/JS207;	4 Months
Average steady-state plasma concentration(Cav,ss)	Average steady-state plasma concentration(Cav,ss) after multiple administration for WJB001/JS207;	4 Months
Steady state peak time(Tmax,ss)	Steady state peak time(Tmax,ss) after multiple administration for WJB001/JS207;	4 Months
Steady state Area under blood concentration - time curve(AUC0-t,ss)	Steady state Area under blood concentration - time curve(AUC0-t,ss) after multiple administration for WJB001/JS207;	4 Months
Accumulation Index ( RAC)	Accumulation Index ( RAC) after multiple administration for WJB001/JS207;	4 Months
Anti-drug antibodies (ADA)	Incidence and titer of anti-drug antibodies (ADA) for JS207；	2 years
Neutralizing Antibody (NAb)	Incidence of Antibody (NAb) for JS207	2 years
Objective response rate(ORR)	Objective response rate(ORR) evaluated by Investigator per RECIST v1.1 in Phase I	3 years
Duration of response (DOR)	Efficacy endpoints : Duration of response (DOR) evaluated by Investigator per RECIST v1.1	3 years
Disease control rate (DCR)	Efficacy endpoints: Disease control rate (DCR) evaluated by Investigator per RECIST v1.1；	3 years
Time of Disease Progression (TTP)	Time of Disease Progression (TTP) evaluated by Investigator per RECIST v1.1	3 years
Progression-free survival (PFS)	Progression-free survival (PFS) evaluated by Investigator per RECIST v1.1	3 years
Overall survival (OS)	Overall survival (OS) evaluated by Investigator per RECIST v1.1	3 years
CCNE1	The correlation between CCNE1 overexpression or amplification and therapeutic efficacy	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	The incidence of biomarkers (such as DNA damage repair and cell cycle related gene variations, PD-L1 expression) in target tumor species and their correlation with therapeutic efficacy	3 years

Collaborators and Investigators

• Sponsor: Wigen Biomedicine Technology (Shanghai) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: April 23, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): May 1, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Albumins; Paclitaxel; Albumin-Bound Paclitaxel; toripalimab; nedaplatin
• Other Study ID Numbers: WJB001-002-I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No