A First-in-Human Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of SYN608, a Poly ADP-ribose Glycohydrolase (PARG) Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 105
- 试验地点
- 2
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
This interventional study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of SYN608 as monotherapy in adult patients with advanced solid tumors
详细描述
This study is a Phase I, open-label, multicentre study of SYN608 administered orally in patients with advanced solid tumors
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Having signed the written Informed Consent Form (ICF);
- •Male or female aged ≥18 years;
- •Life expectancy ≥12 weeks;
- •Eastern Cooperative Oncology Group (ECOG) Performance Score 0 or 1;
- •Patients with histologically or cytologically confirmed locally advanced or metastatic breast cancer, ovarian cancer or other advanced solid tumors who have experienced disease progression, and available standard of care (SOC) therapies had been exhausted;
- •be willing to provide tumor tissue samples (fresh frozen [SF] or previously retained paraffin-embedded [FFPE] tumor tissue samples) or peripheral blood germline DNA or ctDNA sample to detect BRCA mutation, or other deficiency in the Homologous Recombination (HR) pathway (by the detection method of next generation sequencing [NGS])
- •At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;
- •No serious hematological, cardiopulmonary, or liver or kidney diseases other than the primary disease;
- •Adequate organ function and bone marrow function.
排除标准
- •Previous or current use of Poly (ADP) ribose glycohydrolase (PARG) inhibitors;
- •Serious allergy to the study drug or any of its excipients;
- •Current or previous other malignancy unless treated radically and with no evidence of recurrence or metastasis within the past 5 years;
- •Central nervous system (CNS) metastasis or meningeal metastasis with clinical symptoms, or other evidence indicating that CNS metastasis or meningeal metastasis has not been adequately controlled;
- •Patients with Myelodysplastic syndrome (MDS)/Acute myeloid leukemia (AML) or with features suggestive of MDS/AML;
- •Dysphagia or refractory nausea and vomiting, malabsorption, extracorporeal biliary shunts, or gastrointestinal disorders that affect drug absorption, e.g., Crohn's disease, ulcerative colitis, or short bowel syndrome, or other malabsorption conditions;
- •Treatment with an anti-cancer small molecule within 5 half-lives (t1/2), or 2 weeks, whichever is shorter;
- •History of use within 2 weeks prior to the first dose of the study treatment and need to use protocol-prohibited potent inhibitors or potent inducers of cytochrome P450 (CYP) 3A4/BCRP/P-gp during the study;
- •History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease;
- •Serious systemic diseases or laboratory abnormalities or other conditions that, at the Investigator's discretion, will make it unsuitable for the patient to participate in this clinical trial.
研究组 & 干预措施
SYN608 tablet
SYN608 tablet monotherapy
干预措施: SYN608 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: Up to 3 years
MTD is defined as the maximum dose level at which ≤1 patient have dose limiting toxicities (DLTs) during the DLT observation period, and it should be determined with 6 evaluable patients.
Number of participants with Dose Limiting Toxicities (DLTs)
时间窗: From first dose of study treatment until the end of Cycle 1 (each cycle is 21-days)
Severity of adverse events as assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Number of participants experiencing adverse events (AEs)/serious adverse events (SAEs)
时间窗: From time of information consent to 30 days post last dose, up to 3 years
Number of participants with incidence of adverse events and with serious adverse events including changes from baseline in laboratory parameters, vital signs, Electrocardiogram (ECG), and physical examination, etc.
次要结局
- Pharmacokinetic (PK) parameters(Up to 3 years)
- Objective Response Rate (ORR)(Up to 3 years)
- Duration of Response (DoR) and Time to Response (TTR)(Up to 3 years)
- Progression Free Survival (PFS)(Up to 3 years)