NCT05291182招募中1 期
A First-in-human, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of SY-4835 Tablets in Patients With Advanced Solid Tumor
Shouyao Holdings (Beijing) Co. LTD1 个研究点 分布在 1 个国家目标入组 40 人开始时间: 2021年6月28日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Tolerability: Ratio of Dose reductions or interruptions
研究概览
简要总结
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 advanced solid tumors.
详细描述
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 endpoints including the maximum tolerated dose (MTD), Dose-limiting toxicity (DLT), pharmacokinetics (PK) parameters and recommended phase II dose (RP2D), and the safety, tolerability and pharmacokinetics (PK) profiles of SY-4835 are characterized in this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
- •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.
排除标准
- •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.
研究组 & 干预措施
Dose-escalation
Experimental
The study is conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and anti-tumor activity of SY-4835.
干预措施: SY-4835 (Drug)
结局指标
主要结局
Tolerability: Ratio of Dose reductions or interruptions
时间窗: Up to 24 months
Characterization of the safety and tolerability
Adverse events (AE), serious adverse events (SAEs), suspected unexpected serious adverse reaction (SUSAR), physical examination, etc. (CTCAE 5.0 standard)
时间窗: Up to 24 months
Characterization of the safety and tolerability
Incidence rate of dose limiting toxicities (DLTs)
时间窗: cycle 1 (each cycle is 21 days)
Maximum Tolerated Dose(s) (MTD(s)) and recommended phase 2 dose (RP2D(s))
次要结局
- Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria(Up to 24 months)
- Pharmacokinetics (Cmax) for SY-4835(Cycle 1 (each cycle is 21 days))
- Pharmacokinetics (AUC0-t) for SY-4835(Cycle 1 (each cycle is 21 days))
- Pharmacokinetics (t½) for SY-4835(Cycle 1 (each cycle is 21 days))
- Pharmacokinetics (Tmax) for SY-4835(Cycle 1 (each cycle is 21 days))
- Progression Free Survival (PFS)(Up to 24 months)
- Disease control rate (DCR)(Up to 24 months)
- Duration of response (DOR)(Up to 24 months)
研究者
研究点 (1)
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