An Open-Label, Multicenter, Phase I Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of YY201 in Patients With Advanced Solid Tumors and Hematological Malignancies

Inclusion Criteria:

• 1.Patients fully understand and sign ICF, voluntarily participate in the study, andable to follow and complete all study procedures.
• 2.Aged 18-80 years (including upper and lower limits), male or female.
• 3. The standard treatment failure (disease progression after treatment or treatmentside effects not tolerance), or top treatment, or shall not apply to the currentstandard treatment for patients with:
• Surgical excision is confirmed by histology or cytology can't or metastaticpatients with advanced solid tumor;
• Patients with relapsed or refractory hematologic malignancies
• 4. For patients with advanced solid tumors (dose-escalation phase), at least one tumorlesion that could be evaluated according to RECIST, version 1.1; (Dose-expansionphase) At least one measurable tumor lesion according to RECIST, version 1.1 (a tumorthat is located in the previously irradiated area or another locoregional treatmentsite and is generally not considered a measurable lesion unless there is definiteprogression or persistence beyond 3 months of radiation).
• 5. In the dose-expansion phase, enrollment was limited to:
• Advanced solid tumors (predominantly triple-negative breast cancer, pancreaticcancer, and head and neck squamous cell carcinoma) that are sensitive to STAT3therapy;
• Peripheral T-cell lymphoma (PTCL) with STAT3 mutation refractory to or relapsedafter at least one or more lines of systemic therapy;
• For patients with PTCL, computed tomography performed within 28 days before studyentry should show at least one measurable tumor lesion in two verticaldirections, with nodal lesions > 1.5cm in greatest dimension and extranodallesions > 1.0cm (according to the 2014 lugano criteria).
• Relapsed/refractory acute myeloid leukemia that is sensitive to STAT3 therapy,excluding acute promyelocytic leukemia (APL) and other secondary AML (e.g., MDStransformation, CML in blast phase, etc.)
• 6. ECOG physical condition≤1.
• 7. Patients with advanced primary liver cancer should meet the Child-Pugh liverfunction grading: grade A and better grade B (≤7).
• 8. Regular check need to meet the following requirements:
• For advanced solid tumors, adequate bone marrow, liver, and kidney function isrequired:

1. Blood system within 14 days (not received blood transfusions orhematopoietic stimulating factor treatment): Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelet count (PLT) ≥75×10^9/L; Hemoglobin (Hb) ≥85g/L;
2. 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; Aspartateaminotransferase (AST) or less 3 x ULN; Spread to the liver or liver cancerpatient: 5 or less x ULN;
3. Renal function: Creatinine (Cr) or less 1.5 x ULN; Creatinine clearance (Ccr) (calculatedonly when creatinine > 1.5× ULN) ≥50ml/min (calculated according toCockcroft-Gault formula, see Annex 2 of the protocol);
4. Blood coagulation function: Activated partial thromboplastin time (APTT) ≤1.5×ULN; Internationalnormalized ratio (INR) ≤1.5×ULN;
5. Urinary protein: Urine routine /24 hours urine protein qualitative ≤1+; Or urine proteinqualitative ≥2+, 24 hours urine protein < 1g;

• For patients with PTCL, routine blood hemoglobin or 80 g/L, neutrophils acuity 1.0 x 10^9 / L, 75 x 10^9 or higher platelet/L (within 14 days before testwithout blood transfusion or the use of biological stimulating factor);
• For patients with AML, white blood cell counts ≤25 ×10^9/L (Hydroxyurea wasallowed but not for 3 days before administration of the trial drug);
• 9. Agreed to provide archival tumor-tissue specimens or fresh tissue samples (Dose-expansion phase)
• 10.Expected survival of at least 3 months.
• 11. Women of childbearing potential had to have a negative serum or urine pregnancytest within 7 days before the first dose. Fertile male or female patients voluntarilyduring the study period and at the end of the study drug within 30 days of usingeffective birth control methods, such as abstinence, the double protective screen typecuts, condoms, contraceptive method of oral or injected contraceptives, intrauterinedevice, etc. All female patients will be considered fertile unless the female patienthas undergone natural menopause, artificial menopause, or sterilization (e.g.,hysterectomy, bilateral adnophorectomy, or radioactive ovarian irradiation).

Exclusion Criteria:

• 1. The adverse reactions of previous antineoplastic therapy have not recovered toCTCAE 5.0 grade ≤1 (except for toxicities without safety risks judged byinvestigators, such as alopecia, grade 2 peripheral neurotoxicity, and hypothyroidismstable with hormone replacement therapy);
• 2. Clinically symptomatic parenchymal or leptomeningeal metastases that were judged bythe investigator to be ineligible for enrollment and, for AML patients, known centralnervous system (CNS) involvement
• 3. Within 4 weeks before delivery for the first time received chemotherapy, radiationtherapy, biological therapy and endocrine therapy, immune therapy, such as antitumordrugs, 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 weeksbefore 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 traditionalChinese medicines before 2 weeks;
• For peripheral blood leukocyte count (WBC > 25 x 10^9 / L) of the patients,allowing use in treatment of the former and YY201 hydroxyurea control peripheralblood leukocytes;
• Prophylactic intrathecal chemotherapy (cytarabine, dexamethasone, andmethotrexate) unless it is used to prevent central leukemia.
• 4. Received other unlisted investigational drugs or treatments within 4 weeks beforethe first dose;
• 5. Previously received STAT3 inhibitor for anti-tumor treatment;
• 6. Major organ surgery (excluding needle biopsy) within 4 weeks before the first doseof medication or requiring elective surgery during the trial;
• 7. Uncontrolled malignant pleural, ascites, or pericardial effusion that was judged bythe investigator to be ineligible for enrollment;
• 8.Unable to oral drug swallowing, or by the researchers determine the condition of theseriously affect the gastrointestinal tract absorption, including but not limited to,such as inflammatory bowel disease (crohn's disease and ulcerative colitis, forexample), or malabsorption syndrome, or chronic diarrhea;
• 9. Patients who received a potent inducer or inhibitor of CYP3A4 within 1 week beforethe first dose or who required continued treatment with these drugs during the study;
• 10. Patients with active gastric and duodenal ulcer, ulcerative colitis and othergastrointestinal diseases, or unresected tumor with active bleeding, or otherconditions that may cause gastrointestinal bleeding or perforation as judged by theinvestigator;
• 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 acutemyocardial infarction, severe/unstable angina, or coronary artery bypass graftingwithin 6 months before the first dose of medication; Congestive heart failure with NewYork Heart Association (NYHA) grade ≥2; Left ventricular ejection fraction (LVEF) <50%; A history of primary cardiomyopathy, clinically significant prolongation of theQTc interval, or a screening QTc interval >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 Idiabetes 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 electrolyteabnormalities
• 16. Patients with active infection requiring antiinfective treatment or unexplainedfever (body temperature >38.5 ° C) during screening or before the first dose ofmedication;
• 17. Patients with active pulmonary tuberculosis (TB) who are receiving anti-TBtreatment or have received anti-TB treatment within 1 year before the first dose;Known human immunodeficiency virus (HIV) infection; Patients with a history ofhepatitis B were in the stage of active infection (HBsAg positive and HBV-DNA > thedetection limit of the research center); Patients with a history of hepatitis C werein the active infection stage, defined as positive HCV antibody test and HCV RNA abovethe local detection cut-off value;
• 18. Patients who have received hematopoietic stem cell transplantation (HSCT) within 60 days prior to the start of study treatment, or are receiving immunosuppressivetherapy after HSCT at screening, or have graft-versus-host disease (GVHD) requiringdrug control: •Patients treated with fixed oral dose and/or topical corticosteroids for cutaneousGVHD may be enrolled with approval of the Sponsor.
• 19. Women who are pregnant (positive pregnancy test within 14 days before medication)or are breastfeeding.
• 20. Men with fertility needs;
• 21. Patients with known alcohol or drug dependence;
• 22. Patients judged by the investigator that may not be able to comply with all studyprocedures;
• 23. Any other disease, metabolic abnormality, abnormal physical examinations orlaboratory abnormality with significant clinical significance. Investigator reasonablysuspects that the patient has a disease or state that is not suitable for using of thestudy drug, or will affect interpretation of study results, or put the patient at highrisk.