A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile and Preliminary Efficacy of SYH2043 in Patients With Advanced Malignant Tumors

SYH2043-001

The aim of this study is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of SYH2043 in patients with advanced malignant tumors.

2023-03-01

2026-02-01

2026-03-01

Not yet recruiting

Early phase I

367

Inclusion Criteria: * 1. Patients aged 18-75 years (inclusive); * 2. Histological or cytological confirmation of advanced malignant tumors; * 3. Patients who failed or were intolerant to standard treatment or had no standard treatment, and meet the criteria as below of the corresponding stages: * Part A and PK Expansion Stage of part B: advanced malignant tumors; * Cohort extension of part B: solid tumors such as locally advanced/metastatic breast cancer, relapsed/refractory ovarian cancer, locally advanced/metastatic liver cancer, etc; * Part C and D: locally advanced/metastatic breast cancer with histological confirmation of ER+, HER2-; * 4. With at least one measurable lesion according to RECIST v1.1; * 5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1; * 6. Life expectancy greater than 3 months; * 7. Main organs meet the following criteria within 7 days before treatment: * Hematology: no component blood transfusion, human granulocyte colony-stimulating factor (G-CSF), and erythropoietin (EPO) within 2 weeks prior to the investigational drug administration * Absolute neutrophil count (ANC) ≥1.5×10\^9/L; * Platelet count (PLT) ≥90×10\^9/L; * Hemoglobin (HGB) ≥90 g/L or ≥5.6 mmol/L; * Renal Function: Serum creatinine ≤ 1.5×ULN or creatinine clearance rate ≥ 50 mL/min; * Liver function: Total bilirubin (TBIL) ≤ 1.5×ULN, or ≤ 3×ULN for patients with Gilbert syndrome; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤ 2.5×ULN, or ≤ 5×ULN in case of liver metastases; * Coagulation Function: Activated partial thromboplastin time (APTT)≤ 2×ULN; International normalized ratio (INR)≤ 2×ULN; * 8. The serum pregnancy test for women of childbearing potential (WOCBP) is negative within 7 days prior to the first dose of the investigational drug. Patient and his/her spouse must agree to take adequate contraception from signing of ICF to 6 months after the last dose, during which women should be non-lactating and men should refrain from donating sperms; * 9. Patients voluntarily participate in this clinical study, understand the study procedures and sign the ICF. Exclusion Criteria: * 1. Have received anti-tumor treatments such as chemotherapy, radiotherapy, endocrine therapy, targeted therapy, immunotherapy, etc. within 4 weeks before the first dose of the investigational drug; * 2. Have received other unmarketed clinical investigational drugs or treatments within 4 weeks before the first dose of the investigational drug; * 3. Have received major surgery (excluding needle biopsy), or severe unhealed wounds, trauma, etc. within 4 weeks before the first dose of the investigational drug in the study; * 4. Have received glucocorticoids for systemic therapy over 7 days (Prednisone\>10 mg/day or equivalent doses) or other immunosuppressant within 2 weeks before the first dose of investigational drug, and patients who need long-term use these therapies; * 5. Have received potent inhibitors or inducers of CYP3A4 and inhibitors of P-gp within 1 weeks before the first dose of the investigational drug; * 6. The adverse events due to previous anti-tumor treatments without recovering to Grade 1 (except for alopecia; some toxicities may be excluded as judged by the investigator) according to NCI-CTCAE v5.0; * 7. Breast cancer patients with visceral crisis or symptomatic visceral metastasis; * 8. With active central nervous system (CNS) metastasis and/or cancerous meningitis; * 9. Active HBV or HCV infection (HbsAg positive and/or HBcAb positive with HBV DNA ≥ 2000 IU/mL, and HCVAb positive with HCV RNA positive), or HIV positive; * 10. Participants with a history of severe cardiovascular disease; * 11. Inability to swallow medications orally, or conditions that, in the judgment of the investigator, significantly affect gastrointestinal absorption; * 12. Patients who have received a live attenuated vaccine within 2 weeks before the first use of the investigational drug or plan to receive during the study; * 13. Other situations that the investigator considers not suitable for participating in the clinical study.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 367, 'type': 'ESTIMATED'}}

2023-02-17