A First-in-human, Phase 1/2, Open-label, Multi-center, Dose-escalation, Dose-optimization, and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of PARP1 Selective Inhibitor, IMP1734, as Monotherapy in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 156
- 试验地点
- 97
- 主要终点
- Number of subjects with adverse events, treatment emergent adverse events or serious adverse events
研究概览
简要总结
This study investigates the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of EIK1003 in participants with advanced solid tumors.
详细描述
This study will evaluate the safety, tolerability and preliminary efficacy of IMP1734 as monotherapy in patients with recurrent, advanced/metastatic solid tumors. This study includes 2 parts: Part 1 and Part 2. Part 1 includes a monotherapy dose escalation of EIK1003 followed by combination dose escalations in metastatic prostate cancer (mPC), ovarian and breast cancer.
Part 1, dose escalation, the study will identify the maximum tolerated dose (MTD) or maximum achievable dose (MAD) in solid tumor.
Part 2 will explore dose optimization with selection of an optimal dose for future clinical development of EIK1003.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Breast cancer; must have received at least one prior chemotherapy in neoadjuvant/adjuvant/metastatic setting, must have received hormonal therapy if HR+,
- •HGSOC or high grade endometrioid EOC, fallopian tube or primary peritoneal cancer; must have received at least one prior platinum-based chemotherapy for advanced disease
- •mCRPC with ongoing ADT, must have received NHA and up to 1 prior line of taxane chemotherapy
- •Age ≥ 18 years at the time of informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Adequate organ function
- •Life expectancy ≥ 12 weeks
- •Should have evaluable disease as defined by RECIST1.1 and/or CA125 or PSA
- •Female subjects of childbearing potential and male subjects must agree to use an effective method of contraception from study entry up to 6 months after the last dose of IMP1734
- •deleterious or suspected deleterious germline or somatic mutations of select HRR genes
- •up to 1 prior line of PARP inhibitor containing treatment
排除标准
- •Any investigational or approved anti-cancer therapies administered within 28 days/ before the first dose of IMP1734
- •Have received prior PARP1 selective inhibitors
- •Mean resting QTcF > 470 ms or QTcF < 340 ms
- •Active or untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Infections
- •- An active hepatitis B/C infection
- •Any known predisposition to bleeding
- •Unable to swallow oral medications OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition that might impair the bioavailability
研究组 & 干预措施
Cohort 1
IMP1734 monotherapy; oral tablet(s) daily (except for the single-dose period). The maximum trial duration is 3 years after the last participant's first treatment in the trial.
干预措施: IMP1734 (Drug)
结局指标
主要结局
Number of subjects with adverse events, treatment emergent adverse events or serious adverse events
时间窗: Consent to 30 + 7 days post last dose of IMP1734
Number of subjects reporting adverse events or serious adverse events which include any abnormal clinical events, laboratory assessments outside of normal clinical range, abnormal vital signs observed, and any abnormal ECG parameters
Maxim Tolerated Dose or Recommended Dose for Expansion
时间窗: DLT period is from the first dose of the study drug until the last day of the first cycle
Number of patients that experience a DLT or any toxicity which occurs from the time of the first dose of study drug until the end of cycle 1, which is deemed unrelated to the disease.
次要结局
- Overall Response Rate(Through study completion, up to 3 years)
- Pharmacokinetic parameters of IMP1734(Through study completion, up to 3 years)