Advanced solid tumors
Conditions
Interventions
Test group 1:YY001 tablets, 100mg
Test group 2:YY001 tablets, 200mg
Test group 3:YY001 tablets, 300mg
Test group 4:YY001 tablets, 400mg
Test group 5:YY001 tablets, 500mg
Sponsors
Shanghai East Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1.Patients fully understand and sign ICF, voluntarily participate in the study, and able to follow and complete all study procedures. 2. Aged 18-75 years (including upper and lower limits), male or female. 3. Patients with histologically or cytologically confirmed advanced unresectable or metastatic solid tumors (mainly gastrointestinal tumors such as colorectal cancer and gastric cancer, and prostate cancer) 4.The standard treatment failure (disease progression after treatment or treatment side effects not tolerance), or top treatment, or shall not apply to the current standard treatment for patients 5. For patients with advanced solid tumors (dose-escalation phase), at least one tumor lesion that could be evaluated according to RECIST, version 1.1; (Dose-expansion phase) At least one measurable tumor lesion according to RECIST, version 1.1 (a tumor that is located in the previously irradiated area or another locoregional treatment site and is generally not considered a measurable lesion unless there is definite progression or persistence beyond 3 months of radiation); 6. ECOG physical condition=1 7. Patients with advanced primary liver cancer should meet the Child-Pugh liver function grading: grade A and better grade B (=7). 8. With adequate bone marrow, liver and kidney organ function: Blood system within 14 days (not received blood transfusions or hematopoietic stimulating factor treatment) Absolute neutrophil count (ANC) =1.5×10^9/L Platelet count (PLT) =75×10^9/L Hemoglobin (Hb) =85g/L Liver function Total bilirubin (TBIL) =1.5×ULN Alanine aminotransferase (ALT) =3×ULN; Spread to the liver or liver cancer patient: 5 or less x ULN Aspartate aminotransferase (AST) or less 3 x ULN. Spread to the liver or liver cancer patient: 5 or less x ULN Renal function Creatinine (Cr) or less 1.5 x ULN Creatinine clearance (Ccr) (calculated only when creatinine > 1.5× ULN) =50ml/min (calculated according to Cockcroft-Gault formula) Blood coagulation function Activated partial thromboplastin time (APTT) =1.5×ULN International normalized ratio (INR) =1.5×ULN Urinary protein Urine routine /24 hours urine protein qualitative =1+; Or urine protein qualitative =2+, 24 hours urine protein < 1g 9. Expected survival of at least 3 months. 10. Women of childbearing potential had to have a negative serum or urine pregnancy test within 7 days before the first dose. Fertile male or female patients voluntarily during the study period and at the end of the study drug within 30 days of using effective birth control methods, such as abstinence, the double protective screen type cuts, condoms, contraceptive method of oral or injected contraceptives, intrauterine device, etc. All female patients will be considered fertile unless the female patient has undergone natural menopause, artificial menopause, or sterilization (e.g., hysterectomy, bilateral adnophorectomy, or radioactive ovarian irradiation).
Exclusion criteria
Exclusion criteria: 1. The adverse reactions of previous antineoplastic therapy have not recovered to CTCAE 5.0 grade =1 (except for toxicities without safety risks judged by investigators, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stable with hormone replacement therapy); 2. Clinically symptomatic parenchymal or leptomeningeal metastases that were judged by the investigator to be ineligible for enrollment; 3. Within 4 weeks before delivery for the first time received chemotherapy, radiation therapy, biological therapy and endocrine therapy, immune therapy, such as antitumor drugs, with the exception of the following situations: •Nitrosourea or mitomycin C within 6 weeks before first use of study drug; •Oral fluorouracils and small-molecule targeted agents are administered 2 weeks before first use of the study drug or within the five half-lives of the drug, whichever is longer; •Have antitumor indications for the study of the first use of drugs of traditional Chinese medicines before 2 weeks; 4. Received other unlisted investigational drugs or treatments within 4 weeks before the first dose; 5. Previously received EP4 inhibitor (e.g. AN0025(E7046),LY3127760,ONO-4578) for anti-tumor treatment; 6. Major organ surgery (excluding needle biopsy) within 4 weeks before the first dose of medication or requiring elective surgery during the trial; 7. Uncontrolled malignant pleural, ascites, or pericardial effusion that was judged by the investigator to be ineligible for enrollment; 8. Unable to oral drug swallowing, or by the researchers determine the condition of the seriously affect the gastrointestinal tract absorption, including but not limited to, such as inflammatory bowel disease (crohn's disease and ulcerative colitis, for example), or malabsorption syndrome, or chronic diarrhea; 9. Patients who received a potent inducer or inhibitor of CYP3A4 within 1 week before the first dose or who required continued treatment with these drugs during the study; 10. Patients with active gastric and duodenal ulcer, ulcerative colitis and other gastrointestinal diseases, or unresected tumor with active bleeding, or other conditions that may cause gastrointestinal bleeding or perforation as judged by the investigator; 11. Thromboembolic events (including stroke events and/or transient ischemic attack) occurred within 12 months before the first dose of medication; 12. Clinically significant cardiovascular disease, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months before the first dose of medication; Congestive heart failure with New York Heart Association (NYHA) grade =2; Left ventricular ejection fraction (LVEF) 470ms in women and >450ms in men; 13. Patients with active or previous autoimmune diseases with potential recurrence (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), excluding patients with clinically stable autoimmune thyroid diseases and type I diabetes mellitus; 14. Prior immunotherapy with grade =3 irAE or grade =2 immune-related myocarditis; 15. Researchers to determine the clinical significance of 3 or more electrolyte abnormalities 16. Patients with active infection requiring antiinfective treatment or unexplained fever (body temperature >38.5 ° C) during screening or before the first dose of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity;Maximum tolerated dose;Safety index;The recommended phase 2 dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation of therapeutic efficiency;Pharmacokinetic index;Biomarker; | — |
Countries
China
Contacts
Public ContactGuo Ye
Shanghai East Hospital
Outcome results
None listed