Advanced Solid Tumors
Conditions
Interventions
Experimental group:No intra-subject dose escalation is allowed during the DLT observation period (C0D1~C1D21).After the DLT observation period, a subject may escalate to a dose level higher than the d
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Research participants must meet all of the following inclusion criteria in order to be enrolled in this trial: 1. Voluntarily participate in clinical research and sign a written informed consent form, and be able to comply with the procedures related to clinical visits and research; 2. Men or women aged 18 or above who sign the informed consent form; 3. Patients with advanced solid tumors diagnosed by histology or cytology, who have failed standard treatment, have no standard treatment plan, or are currently not suitable for standard treatment; 4. The score of the Eastern Cooperative Oncology Group (ECOG) is 0 or 1; 5. Expected survival time is not less than 3 months; 6. The bone marrow reserve and organ function level must meet the following requirements (no supportive treatment such as blood components or growth factors received within 7 days prior to laboratory testing): Bone marrow reserve: neutrophil count (ANC)>=1.5 × 10 ^ 9/L; platelet count (PLT)>=90 × 10 ^ 9/L; hemoglobin (HGB)>9.0 g/dL; Coagulation function: International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (APTT)=50 mL/min (using Cockcroft Gault formula) or serum creatinine=50%; 7. There is at least one measurable lesion (according to RECIST v1.1 standard); 8. Qualified subjects (male and female) with fertility must agree to use reliable contraceptive methods (such as hormones, barrier methods, or abstinence) with their partners for at least 3 months during the trial period and after the last use of medication; Female subjects of childbearing age must have a negative serum pregnancy test within 7 days prior to the first use of the investigational drug.
Exclusion criteria
Exclusion criteria: Patient who meets any of the following criteria should be excluded from this study: 1.Has received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immune checkpoint inhibitor therapy, other anti-tumor treatments, or other un-marketed investigational drugs within 4 weeks prior to first dose of YY2201 (or within 5 half-lives of treatment, whichever is shorter), except for the following items: Have used nitrosourea or Mitomycin C within 6 weeks prior to first dose of Y2201. Have used oral fluorouracil and small molecule targeted drugs within 2 weeks or 5 half-lives of the drugs prior to first dose of YY2201 (whichever is longer). Have used herbal therapy with anti-tumor indications are within 2 weeks prior to first dose of YY2201. 2.Has prior (within 2 years before screening) or concurrent other malignancy (except for cured basal cell carcinoma of the skin, carcinoma in situs of cervix, ductal carcinoma in-situ, and prostate cancer which not requiring treatment). 3.Has undergone major organ surgery (excluding biopsy) or have had significant trauma within 4 weeks prior to first dose of YY2201 or required elective surgery during the study period. 4.Is taking (or cannot be stopped at least 1 week prior to first dose of YY2201) any drug that is known to strongly or moderately inhibit or induce CYP2C8 and CYP3A4. 5.The adverse reactions of previous anti-tumor treatments have not yet recovered to grade =1 (except for toxicity judged by the investigator to have no safety risk, such as alopecia and fantigue). 6.Has spinal cord compression or brain metastases and requiring corticosteroid therapy at a dose of more than 10 mg prednisone or equivalent per day for at least 4 consecutive weeks prior to initiation of study treatment (unless asymptomatic, treated, and stable) or a history of leptomeningeal metastases. 7.Any gastrointestinal tract related conditions that may affect the drug absorption as judged by the investigator, such as nausea and vomiting that are difficult to control, intestinal obstruction, gastric outlet obstruction, unable to swallow preparations, previous major gastrointestinal resection and so on. 8.Has active infection 1 week before the first dose of YY2201 and currently need systemic anti-infection treatment. 9.HIV infection, or active HBV infection or active HCV infection, with the exception: a) Patients with serologic evidence of chronic HBV infection and have HBV viral load below the limit of quantification with normal liver function. b) Patients with serologic evidence of HCV infection and have negative hepatitis C virus RNA test results. 10.History of serious cardiovascular and cerebrovascular diseases, including but not limited to: Severe cardiac rhythm or conduction abnormality, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrioventricular block, etc., PR interval > 250 ms; Thromboembolic events requiring therapeutic anticoagulation, or subjects with a venous filter; Patients with Class III~IV cardiac insufficiency according to the criteria of New York Heart Association (NYHA); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other grade 3 or higher cardiovascular and cerebrovascular events within 12 months prior to the first dose; QT interval corrected through Fridericia's formula (QTcF) prolongation (male > 450 ms, female > 470 ms); any factors that increase the risk of QTc prolongation and arrhythmia, such as heart failure, congen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics;Safety and tolerability;Optimal recommended dosage; | — |
Secondary
| Measure | Time frame |
|---|---|
| Electrocardiogram;Vital signs;Pharmacodynamics; | — |
Countries
China
Contacts
Public ContactJian Zhang
Fudan University Shanghai Cancer Center
Outcome results
None listed