Status:
UNKNOWN
A Phase I Study of SY-4835 in Patients With Advanced Solid Tumors
Lead Sponsor:
Shouyao Holdings (Beijing) Co. LTD
Conditions:
Advanced Solid Tumor
Eligibility:
All Genders
18-75 years
Phase:
PHASE1
Brief Summary
This is a phase 1, open-label, single-arm, first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK) and anti-tumor activity of SY-4835 administered orally in patients with adva...
Detailed Description
This study is a first-in-human phase I study of SY-4835, a potent WEE1 inhibitor, in patients with advanced solid tumor. Dose-escalation study is conducted to evaluate primary endpoints and secondary ...
Eligibility Criteria
Inclusion
- For inclusion in this study, patients must fulfil the following criteria:
- Must understand andvoluntarily sign the informed consent form, willing to follow and able to complete all study procedures.
- Male or female (age of 18\~75 years old ).
- Eastern Collaboration Oncology Group (ECOG) performance status (PS) scored of 0-1.
- Estimated life expectancy ≥3 months.
- Histological or cytological confirmation of a advanced solid tumor, that failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist.
- At least 1 measureable lesion for solid tumors assessed using RECIST 1.1.
- Patients must have adequate organ function as defined below (no supportive treatment for the following parameters within 7 days prior to testing):
- Liver function:
- Patients without hepatic metastasis, aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 times institutional upper limit of normal (ULN), total bilirubin (TBIL) ≤ 1.5 times ULN; Patients with hepatic metastasis, AST, ALT ≤ 5 times ULN, TBIL ≤ 1.5 times ULN; Patients with hepatoma carcinoma, AST and ALT ≤ 5 times ULN, TBIL ≤ 2.5 times ULN.
- Bone marrow function:
- Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L; Platelets (PLT) count ≥ 75×10\^9/L; Hemoglobin (HB) ≥ 80 g/L.
- Renal function:
- Creatinine clearance ≥ 45 mL/min or serum creatinine ≤ 1.5 times ULN.
- Coagulation function:
- Activated partial thromboplastin time (APTT) ≤ 1.5×ULN; International Normalized ratio (INR) ≤ 1.5×ULN.
- Women of childbearing age performed a serum pregnancy test within 7 days before the initiation of treatment, and agreed to adopt a reliable and effective contraceptive method during the trial and within 90 days after the final administration of the study drug.
Exclusion
- Patients must not enrol in this study if any of the following exclusion criteria are fulfilled:
- Have received chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor therapy within 3 weeks prior to the first use of the study drug, except for the following:
- Nitrosourea or mitomycin C were used within 6 weeks prior to the first use of the study drug; Oral fluorouracil and small molecule targeted drugs were used within 2 weeks or within 5 half-lives prior to the first use of the study; Chinese medicines were used within 2 weeks prior to the first use of the study drug.
- Have received an unmarketed clinical investigational drug or treatment within 4 weeks prior to the first use of the study drug.
- Had major organ surgery (excluding needle biopsy) or had significant traumatism within 4 weeks prior to the first use of study drug.
- History of any WEE1 inhibitor treatment.
- With the exception of alopecia and ≤ Grade 2 peripheral neuropathy, any unresolved toxicities from prior treatment ≤ Grade 1 according to the Common Terminology Criteria for Adverse Events (CTCAE) at the time of starting study treatment.
- Evidence of central nervous system (CNS) metastases accompanied with clinical symptoms, or other evidence of uncontrolled CNS metastases judged by investigators that the patient should not participate in the study.
- Patients have serous effusion (such as pleural effusion, peritoneal effusion, pericardial effusion, etc.) with clinical symptoms, effusions will still increase after 2 weeks of conservative treatment (excluding drainage).
- Patients with active uncontrolled systemic bacterial, viral, or fungal infection despite optimal treatment.
- Active hepatitis B (HBsAg-positive and HBV-DNA ≥ 2000 IU/ mL), Hepatitis C virus infection (HCVAb-positive and HCV-RNA ≥ 1000 IU/ml); Human immunodeficiency virus antibody (HIV Ab) positive; Active syphilis.
- Have serious cardiovascular and cerebrovascular diseases, including but not limited to:
- Severe arrhythmias or abnormal cardiac conduction, such as ventricular arrhythmias requiring clinical intervention, degree ii-iii atrioventricular block, etc; Mean resting corrected QT interval (QTcF) \> 470 msec obtained from 3 electrocardiograms (ECGs); Had acute coronary syndrome, congestive heart failure, aortic dissection, or other grade 3 or higher cardio-cerebrovascular events within 6 months prior to the first use of study drug; Heart failure (New York Heart Association, NYHA) class ≥ II or left ventricular ejection fraction (LVEF) \< 40 %; Hypertension remains uncontrolled after aggressive antihypertensive therapy. Uncontrolled hypertension was defined as systolic blood pressure \> 185 mmHg and/or diastolic blood pressure \> 110 mmHg measured on 3 repetitions at least 10 minutes apart.
- Prescription or non-prescription drugs known as moderate to strong inhibitors / inducers of CYP3A4 and CYP2D6 within 7 days prior to the first dose of study treatment.
- Patients with alcohol and/or drug dependence.
- Women who are breastfeeding.
- Patients suffering from conditions which are likely to adversely affect gastrointestinal motility.
- Patients with malignancies other than tumors treated in this study (except: malignancies that are cured and have not recurred within 3 years prior to study entry; completely resected basal cell and squamous cell skin cancer; completely resected carcinoma in situ of any type).
- The investigator considers that the subject has a history of other serious systemic diseases or other reasons and is not suitable to participate in this clinical study.
Key Trial Info
Start Date :
June 28 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 28 2024
Estimated Enrollment :
40 Patients enrolled
Trial Details
Trial ID
NCT05291182
Start Date
June 28 2021
End Date
December 28 2024
Last Update
February 2 2024
Active Locations (1)
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1
Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Shanghai, Shanghai Municipality, China, 200127