Phase I Study of WJ47156 Monotherarpy and in Combination With Other Therapy in Advanced Solid Tumors
- Conditions
- Advanced Malignant Solid Tumors
- Registration Number
- NCT06571422
- Lead Sponsor
- Shanghai Junshi Bioscience Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not yet recruiting
- Sex
- All
- Target Recruitment
- 93
<br><br> 1. Male or female, 18 to 75 years old (inclusive) at the time of signing the ICF;<br><br> 2. Patients with histologically or cytologically confirmed advanced malignant solid<br> tumors;<br><br> 3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;<br><br> 4. Life expectancy = 12 weeks;<br><br> 5. At least one measurable lesion according to RECIST 1.1;<br><br> 6. Adequate organ function ;<br><br> 7. Female or male patients of childbearing potential must agree that they have no<br> intention to become pregnant during the study and for 6 months after the last dose,<br> and to use highly effective contraceptive methods with their partners; );<br><br> 8. Voluntary participation with full informed consent by signing an written informed<br> consent, and with good compliance.<br><br>Exclusion Criteria<br><br> 1. CNS metastasis;<br><br> 2. Pleural effusion, peritoneal effusion or pericardial effusion with clinical symptoms<br> or requiring repeated treatment (e.g., puncture or drainage);<br><br> 3. Unable to swallow tablets, intestinal obstruction, or other factors affecting the<br> administration and gastrointestinal absorption of tablets<br><br> 4. For the combination therapy, patients will not be enrolled in this study if they<br> meet any of the following criteria:<br><br>(1)Imaging findings at screening showing tumor encasement of a major vessel or<br>significant necrosis and cavity, which may lead to a hemorrhagic risk as judged by the<br>investigator; (2)Patients with active autoimmune diseases requiring systemic treatment<br>(e.g., corticosteroids or immunosuppressive drugs) within 2 years prior to the first<br>dose, including but not limited to systemic systemic lupus erythematosus, multiple<br>sclerosis, rheumatoid arthritis, inflammatory bowel disease, vasculitis, etc. However,<br>hypothyroidism, hypoadrenalism or hypopituitarism controlled only by hormone replacement<br>therapy, Type I diabetes mellitus not requiring systemic treatment, psoriasis or vitiligo<br>are allowed; (3)Previously treated with anti-PD-1/L1 therapy; (4)History of interstitial<br>lung disease or previous history of non-infectious pneumonia treated with<br>corticosteroids, or evidence of active pneumonia on imaging at screening;<br>(5)Gastrointestinal perforation, fistula, abdominal abscess and ulcerative disease or<br>history of digestive system ulcerative disease within 6 months prior to the first dose<br>(patients with stable ulcer as assessed by the investigator may be considered for<br>enrollment); (6)Presence of serious, unhealed, or open wounds, active ulcers, or<br>untreated fractures; (7)History of gastrointestinal bleeding within 6 months prior to<br>enrollment, or clear tendency of gastrointestinal bleeding (including hemorrhagic risk of<br>severe esophageal-gastric varices, locally active digestive tract ulcerative lesion, and<br>persistent positive fecal occult blood); (8)Clinically significant hemoptysis or tumor<br>bleeding for any reason within one month prior to the first dose; (9)History of obvious<br>bleeding tendency or severe coagulation dysfunction; (10)Severe drug-related adverse<br>events leading to permanent discontinuation of the drug product or bevacizumab or its<br>analogues; (11)Use of antiplatelet therapy or anticoagulant therapy for treatment within<br>14 days prior to the first dose; (12)Long-term treatment with nonsteroidal<br>anti-inflammatory drugs is permitted for brief periods of time to relieve symptoms such<br>as fever or pain.<br><br> 5. Uncontrolled hypertension (systolic blood pressure = 150 mmHg and/or diastolic blood<br> pressure > 100 mmHg) or history of hypertensive crisis or hypertensive<br> encephalopathy; 6. Severe cardiovascular disease, including but not limited to,<br> myocardial infarction, severe/unstable angina, congestive heart failure (New York<br> Heart Association [NYHA] class = 2), clinically significant supraventricular or<br> ventricular arrhythmia requiring drug intervention, aortic aneurysm requiring<br> surgical repair, any arterial thrombosis/embolism event, Grade 3 or higher (Common<br> Terminology Criteria for Adverse Events [CTCAE] v5.0) venous thrombosis/embolism<br> event, transient ischemic attack, cerebral vascular accident; Left ventricular<br> ejection fraction (LVEF) < 50% by echocardiography. Corrected QT interval (QTc) ><br> 480 ms (calculated using the Fridericia method; if QTc is abnormal, measure 3 times<br> at an interval of 2 minutes and use the average).<br><br> 7. Serious infection (CTCAE Grade > 2) within 28 days prior to the first dose, such as<br> serious pneumonia, bacteremia, infection and complications requiring<br> hospitalization; or active infection or unknown cause of fever (>38.5?) requiring<br> systemic anti-infection treatment within 2 weeks prior to the first dose (as judged<br> by the investigator, patients with tumor-induced fever can be enrolled);<br><br> 8. Presence of active tuberculosis, hepatitis B (positive for hepatitis B surface<br> antigen [HBsAg] and HBV DNA higher than the lower limit of detection in the study<br> site), hepatitis C (positive for HCV antibody [HCVAb] and HCV RNA higher than the<br> lower limit of detection in the study site);<br><br> 9. History of immunodeficiency, including human immunodeficiency virus (HIV) positive<br> test, or history of known allogeneic organ transplantation or allogeneic<br> hematopoietic stem cell transplantation;<br><br> 10. History of another primary malignant tumor, with the exception of malignant tumors<br> (e.g., basal cell carcinoma of skin and squamous cell carcinoma of skin) who have<br> received potentially curative therapy (more than 5 years) without known active<br> disease prior to the first dose, without potential risk for recurrence ;<br><br> 11. Toxicity of previous antitumor therapy has not been recovered to CTCTAE Grade = 1 or<br> to the level specified in the inclusion/exclusion criteria, with the exception of<br> the following: related toxicities that are well controlled as judged by the<br> investigator and do not affect the safety and compliance of the study treatment, and<br> can be screened after confirmation by the Sponsor;<br><br> 12. Prior use of the following drugs or therapies before the first dose:<br><br> 1. Having received chemotherapy, immunotherapy or other anti-tumor therapy or other<br> investigational drug within 21 days prior to the first dose, or having received oral<br> fluorouracil, small-molecule targeted drugs or Chinese herbal products for antitumor<br> indications within 14 days prior to the first dose;<br><br> 2. Major surgery, radiation therapy (with the exception of palliative radiation to a<br> localized bone or brain lesion, which may be completed up to 14 days prior), or any<br> other minor surgical procedure, excluding placement of vascular access devices,<br> within 28 days prior to the first dose; and any biopsy or other minor procedure<br> within 7 days prior to the first dose.<br><br> 3. In the combination therapy phase, patients who have received systemic treatment with<br> corticosteroids (more than 10 mg/day prednisone or equivalent) or other<br> immunosuppressants within 2 weeks prior to the first dose are allowed to use inhaled<br> or topical steroids or systemic prednisone =10 mg/day and equivalent drug product;<br><br> 4. Having received any live vaccine or attenuated live vaccine within 28 days prior to<br> the first dose or requiring to be vaccinated with live vaccine or attenuated live<br> vaccine during the study (only for patients in combination therapy phase);<br><br> 13. Patien
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1.DLT;2?AE;3?SAE;4.MTD;5.RP2D
- Secondary Outcome Measures
Name Time Method 6.ORR;7.DOR;8.DCR;9.PFS;10.OS;11.Peak concentration(Cmax);12.The time to receive Cmax(Tmax);13. Area under the plasma concentration-time curve (AUC0-t, AUC0-8);14.Apparent volume of distribution (Vd/F);15.Apparent clearance (CL/F);16.Terminal half-life (t1/2);17.Steady-state peak concentration(Cmax,ss);18.Plasma trough concentration at steady state(Cmin,ss);19.Mean plasma concentration at steady state(Cav,ss);20.The time to receive Cmax at steady state(Tmax,ss);21.Area under the plasma concentration-time curve at steady state (AUC0-t, ss);22.Accumulation factor(RAC);23.Fluctuation coefficient(FD)