Introduction

TY-302 capsule is a CDK4/6 inhibitor

The indications for this study are HR+/HER2- locally advanced or metastatic breast cancer and other advanced solid tumor or blood cancer.

Primary purpose: evaluate the safety, tolerance, MTD, and DLT of TY-302 capsule in advanced solid tumor patients, and determine the RP2D.

Secondary purpose: 1) evaluate the PK characteristic of TY-302 capsule in single and repeated drug administration; 2) preliminary evaluation of the anti-tumor effect of TY-302 capsule (ORR, DoR, DCR, CBR, and PFS); 3) investigate the relationship between biomarker and efficacy

Study design

Inclusion criteria

1. At least one measurable disease according to RECIST 1.1.
2. ECOG score ≤ 1
3. Life expectancy of at least 3 months
4. Histological or cytological confirmation of advanced solid tumors (except small cell lung cancer and eye cancer) that have no standard therapy, have failed standard therapy, or are intolerant of standard therapy

5. Good organ function, including:

1. Liver function: Total bilirubin (TBIL) ≤ 1.5×ULN, Glutathione aminotransferase (ALT) ≤ 2.5×ULN,and Glutathione transaminase (AST) ≤ 2.5×ULN [For patients with liver metastases, this can be relaxed to TBIL ≤ 1.5×ULN, ALT ≤ 5×ULN, and AST ≤ 5×ULN]
2. Renal function: Blood creatinine (Cr) ≤ 1.5×ULN,and Creatinine clearance ≥ 50 mL/min
3. Blood count: PLT ≥ 75×109/L, ANC ≥ 1.5×109/L, and Hb ≥ 90g/L
4. Heart function: Echocardiographic left heart ejection fraction (LVEF) ≥ 50%, and QTcF interval ≤ 470 ms

6.Female patients not of childbearing potential, female patients of childbearing potential with a negative pregnancy test and a commitment to adequate and effective contraception or abstinence from the screening period until 6 months after the last dose, or male patients with a commitment to adequate and effective contraception or abstinence from the screening period until 6 months after the last dose

7.Able to comprehend and willing to sign an informed consent form (ICF) and have the willingness and ability to complete the entire trial process

Exclusion criteria

1. Patients who received prior treatment with any CDK4/6 inhibitor (e.g., Palbociclib, Ribociclib, Abemaciclib, Trilaciclib/G1T38, SHR6390, and Pyrotinib)
2. Known or suspected allergy to investigational productsor other components of its preparation
3. Having received allogeneic transplantation such as stem cell transplantation, bone marrow transplantation or liver transplantation
4. Known uncontrollable infectious disease, congenital or acquired immunodeficiency disease, active hepatitis, or other active infection, or an unstable or severe intercurrent disease at the time of screening
5. Known history of alcohol addiction or drug abuse
6. Any of the following within 6 months prior to the first dose of investigational product: myocardial infarction, severe/unstable angina, sustained arrhythmia with CTCAE v5.0 ≥ 2, atrial fibrillation of any grade, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure with CTCAE v5.0 ≥ 2, cerebrovascular accident
7. Serious gastrointestinal dysfunction, or disease that may affect the intake, transport, or absorption of investigational product
8. Received cytotoxic chemotherapy drugs or proprietary Chinese medicines with antitumor efficacy approved by the state within 4 weeks prior to the first dose of investigational product
9. Having received anti-tumor hormonal drugs, small molecule targeted drugs, radiotherapy, radioimmunotherapy, immunotherapy, or other biological therapies within 4 weeks prior to the first dose of investigational product
10. Received whole blood, PLT, or red blood cell (RBC) transfusions within 7 weeks prior to the first dose of investigational product
11. With primary central nervous system (CNS) malignancies, or CNS metastases that have failed local treatment. However, patients with brain metastases without any clinical symptoms may be considered for enrollment
12. Having received major surgery within 8 weeks prior to the first dose of the investigational product
13. The toxicity caused by previous anti-tumor therapy has not recovered to ≤CTCAE grade 1 (CTCAE 5.0) with AE ≥ 2
14. Known history of severe central nervous system disease
15. Have been receiving and cannot discontinue a drug or treatment prohibited by the protocol at least 2 weeks prior to the first dose of investigational product and during the study period
16. Patients with any evidence ofbleeding constitution or history, or patients who have been receiving anticoagulant therapy
17. Other conditions are considered by investigators as unsuitable to participate in this study.

Researcher information