solid tumors
Conditions
Interventions
dose escalation group:SPH4336 tablets
dose expansion group:SPH4336 tablets
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18 to 65 years; 2. Histologically or cytologically confirmed advanced solid tumors (including but not limited to breast cancer, central nervous system primary tumors/metastatic tumors, etc.) with at least one of the following conditions: Failed standard treatment; Cannot tolerate standard treatment; There is no standard treatment; Lack of financial means for standard care; Patients refuse standard care; 3. The presence of at least one target lesion according to RECIST (version 1.1) evaluation criteria (dose-expansion phase only); 4. The ECOG (performance status, PS) score is 0 - 1; 5. Expected survival time >=3 months; 6. Good organ function level: (1) LVEF>=50%; QTcF=2.0x10^9/L; PLT>=100x10^9/L; Hb>=110 g/L; (2) TBIL<=1.5xULN; ALT and AST<=1.5xULN; If liver metastasis was present, ALT and AST<=5xULN; Cr<=1xULN; (3) INR<=2xULN or APTT<=2.5xULN (if the subject is receiving anticoagulant therapy, PT and APTT are required to be within the expected range of anticoagulant therapy); 7. Can comply with the trial protocol as judged by the investigator; 8. Volunteer to participate in the clinical trial, understand the study procedures and be able to sign the informed consent in person.
Exclusion criteria
Exclusion criteria: 1. Previous use or ongoing use of anti-tumor drugs targeting CDK4/6; 2. Received any other antitumor therapy (including radiotherapy, chemotherapy, molecular targeted therapy, immunotherapy or other biologic therapy) within 4 weeks; Note: Bisphosphonates and local remission therapy for bone metastases, such as local radiotherapy, are permitted within 4 weeks before screening. 3. Had a major surgery within 6 weeks prior to screening or was scheduled to have a major surgery within 12 weeks after starting the study drug; 4. Enrolled in other clinical trials and received treatment as a subject within 4 weeks before participating in this trial; 5. Toxicity on laboratory tests of CTCAE grade II or greater (according to CTCAE version 5.0) due to previous treatment; 6. The presence of third space effusion (e.g. massive pleural effusion and ascites) that cannot be controlled by drainage or other methods; 7. Long-term steroid treatment (except topical glucocorticoids) is required; 8. Inability to swallow, chronic diarrhea and intestinal obstruction, with multiple factors affecting drug administration and absorption; 9. Uncorrected hypokalemia and/or hypomagnesemia were present at the time of enrollment; 10. Patients with allergies or a history of severe allergies; 11. HBV infection and HBV copy number >=500 copies /ml or the lower limit of laboratory detection; HCV infection and HCV copy number >=10^3 copies /ml; A history of immunodeficiency, including being HIV positive, or having other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 12. Cardiac criteria: Presence of factors that can cause QTc prolongation or arrhythmia such as congestive heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, and other concomitant medications known to prolong the QT interval. The presence of any unstable cardiovascular disease (including New York College of Cardiology NYHA class ? or ?, unstable angina, and a history of myocardial infarction within one year); 13. Uncontrolled hypertension (systolic blood pressure >=150 mmHg and/or diastolic blood pressure >=100 mmHg) after treatment, or hypertensive crisis or hypertensive encephalopathy in the past; 14. Severe lung disease (previous or combined history of severe interstitial lung disease, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, symptomatic bronchospasm); 15. Treatment with a potent or moderate CYP3A4 inhibitor or inducer (other than topical glucocorticoids) is ongoing; 16. Positive baseline pregnancy test for pregnant or lactating women or fertile women; (Infertile women were defined as those who were at least 50 years of age, had not taken hormone therapy and had stopped menstruating for at least 12 months; or have been sterilized.); 17. Women of childbearing age who were unwilling to use effective contraception throughout the trial period and men with partners of childbearing age; 18. Concomitant diseases (such as severe hypertension, diabetes, thyroid disease, etc.) that, in the judgment of the investigator, seriously endanger the patient's safety or affect the patient's completion of the study; 19. A clear history of neurological or psychiatric disorders, including epilepsy or dementia; 20. Other circumstances in which the investigator considers it inappropriate to participate in the study.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| PK characteristics;objective response rate;biomarkers; | — |
Primary
| Measure | Time frame |
|---|---|
| safety and tolerability; | — |
Countries
China
Contacts
Public ContactWang Yongsheng, Jiang Yu
Outcome results
None listed