Dose Escalation and Expansion Study of SYH2043 in Patients With Advanced Malignant Tumors

Trial Title: Dose Escalation and Expansion Study of SYH2043 in Patients With Advanced Malignant Tumors

NCT ID: NCT05728541

Condition: Advanced Malignant Tumors

Conditions: Official terms:
Neoplasms

Study type: Interventional

Study phase: Phase 1

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: SYH2043
Description: Patients will receive SYH2043 once everyday on day 1-21 of each 28-day cycle
Arm group label: SYH2043

Summary: 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.

Detailed description: This study is an open-label, single-arm, multi-center Phase I clinical study, which includes four stages: A: Dose-escalation Stage: The dose escalation stage is divided into 5 dose levels, and a Bayesian Optimal Interval Design (BOIN) including accelerated titration will be used for dose escalation. B: PK Expansion Stage: Two or three dose groups will be selected for PK expansion; After PK extension the cohort extension study will be conducted as required, and will include 4 cohorts according to the tumor types. C: Combination dose Escalation: This study will use a 3+3 design with up to 2 dose escalation cohorts at increasing levels. D: According to the results of stage C, 1-2 combination doses will be selected for combination dose expansion, and Simon 2 stage was adopted for the expansion stage.

Criteria for eligibility:
Criteria:
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.

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: Cancer Hospital Chinese Academy of Medical Sciences

Address:
City: Beijing
Zip: 100021
Country: China

Contact:
Last name: Binghe Xu, Doctor

Phone: +86-10-67781331
Email: xubinghe@medmail.com.cn

Start date: March 1, 2023

Completion date: March 1, 2026

Lead sponsor:
Agency: CSPC Ouyi Pharmaceutical Co., Ltd.
Agency class: Industry

Source: CSPC Ouyi Pharmaceutical Co., Ltd.

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05728541