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

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. 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