ZE94-0605在晚期实体瘤患者中的研究，包含剂量扩展队列。
2026年7月28日 更新者：Eilean Therapeutics
ZE94-0605在已耗尽所有治疗选择的实体瘤患者中的I期研究及随后在选定实体瘤患者中扩展为两个剂量组
针对已用尽所有治疗方案且随后在特定实体瘤患者中扩展为两个剂量队列的实体瘤患者进行的ZE94-0605的1期研究。
研究概览
详细说明
这项1期研究将重点关注所有无替代疗法的实体瘤患者的剂量递增，以确定最大耐受剂量（MTD），随后在具有CCNE1扩增（或后续确定的其他分子/细胞特征）的实体瘤患者中进行两个剂量水平的扩展（MTD和一个低于MTD的剂量），以符合项目Optimus制定的指南。
研究类型
介入性
注册 (估计的)
60
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习联系方式
- 姓名：Ekaterina Dokukina
- 电话号码：+1 858 353 4108
- 邮箱：kdokukina@eilenther.com
学习地点
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Tashkent、乌兹别克斯坦、100109
- 招聘中
- Republican Specialized Scientific and Practical Medical Center of Oncology and Radiology Uzbekistan
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接触：
- Dilshod Rafiev
- 电话号码：+998888926569
- 邮箱：dilshod.rafiev@cancercenter.uz
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New South Wales
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Kogarah、New South Wales、澳大利亚、2217
- 招聘中
- St. George Private hospital
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接触：
- Meet Desai
- 电话号码：+61285945785
- 邮箱：clinicaltrials.sgp@ramsayhealth.com.au
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South Australia
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Bedford Park、South Australia、澳大利亚、5042
- 招聘中
- SOCRU - Southern Oncology Clinical Research Unit
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接触：
- Ashlee Hearnden
- 电话号码：+61 491 679 039
- 邮箱：ashlee.hearnden@socru.org.au
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
描述
纳入标准：
第1阶段剂量递增队列：
年龄≥18岁，经病理学确诊的晚期、不可切除或转移性实体瘤患者，对已知对其病情有临床获益的现有疗法耐药或不耐受。
第1阶段扩展队列：
年龄≥18岁，经病理学确诊的晚期、不可切除或转移性实体瘤患者，对已知对其病情有临床获益的现有疗法耐药或不耐受，或拒绝接受该疗法，且具有CCNE1扩增。
- ECOG体能状态评分为0-1。
- 根据以下定义具备足够的终末器官功能：肌酐清除率>60毫升/分钟，AST/ALT<正常值上限的3倍，总胆红素<正常值上限的1.5倍（吉尔伯特病患者除外）。
- 绝对中性粒细胞计数（ANC）必须≥1.5×10⁹/升，血小板计数必须≥100×10⁹/升。
- 对于有生育潜力的女性患者，愿意从筛选访视开始，在整个研究治疗期间及末次研究药物给药后30天内，避免异性性交或使用方案推荐的有效避孕方法。
- 对于有生育潜力的男性患者，若与有生育潜力的女性发生性行为，愿意从研究治疗开始，在整个研究治疗期间及末次研究药物给药后90天内，避免异性性交或使用方案推荐的有效避孕方法。男性还必须从研究治疗开始，在整个研究治疗期间及末次研究药物给药后90天内，避免捐献精子。
- 愿意遵守预定的访视、给药计划、影像学检查、实验室检测、其他研究程序和研究限制。
排除标准：
- 有其他恶性肿瘤病史，但以下情况除外：已充分治疗的局部皮肤基底细胞癌或鳞状细胞癌、宫颈原位癌、浅表性膀胱癌、无症状且无已知转移性疾病的前列腺癌，或在入组前≥2年未经治疗已完全缓解的任何其他癌症，或预期寿命为24个月且不需要可能混淆本研究数据解读的治疗。若发生此类情况，必须在筛选入组前与医学监查员讨论。
- 已知活动性丙型肝炎、乙型肝炎或HIV感染。
- 妊娠或哺乳期。
- 同时参与以治疗为目的的研究性药物试验，定义为在研究治疗开始前14天内接受过既往研究治疗。
- 无法耐受口服药物，包括严重影响胃肠道功能的症状性疾病，如炎症性肠病或胃/小肠切除术。
- 在药物5个半衰期内接受过研究性药物（任何适应症）的患者；若药物半衰期未知，患者必须在首次研究治疗给药前等待1周。研究性药物指未获得美国食品药品监督管理局（FDA）批准适应症的药物。
- 存在心理、家庭、社会或地理因素、其他重大医学状况、实验室异常，以致无法提供知情同意、遵循方案、可能妨碍研究治疗和随访的依从性，或可能混淆试验结果解读的患者。
- 存在以下情况的患者将被排除：未控制的并发疾病，包括但不限于症状性充血性心力衰竭、不稳定型心绞痛、严重心律失常、纽约心脏病协会（NYHA）III级或IV级心力衰竭、严重未控制的室性心律失常，或心电图显示急性缺血或活动性传导系统异常。存在可能妨碍联合用药安全性评估的医学合并症的患者不应入组。
- QTc间期≥470毫秒的患者（除非患者装有起搏器）。不完全性或完全性右/左束支传导阻滞的患者，若经心脏科评估确认适合入组，可参与研究。
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：顺序分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Phase 1a Dose Level -1: ZE94-0605 50 mg QD
Optional dose-reduction cohort.
Participants will receive ZE94-0605 50 mg orally once daily in the fasted state in continuous 28-day cycles.
This dose level will be evaluated only if Dose Level 1 is not tolerated.
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口服胶囊每日一次
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实验性的：Phase 1a Dose Level 1: ZE94-0605 100 mg QD
Participants will receive ZE94-0605 100 mg orally once daily in the fasted state in continuous 28-day cycles.
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口服胶囊每日一次
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实验性的：Phase 1a Dose Level 2: ZE94-0605 200 mg QD
Participants will receive ZE94-0605 200 mg orally once daily in the fasted state in continuous 28-day cycles.
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口服胶囊每日一次
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实验性的：Phase 1a Dose Level 3: ZE94-0605 350 mg QD
Participants will receive ZE94-0605 350 mg orally once daily in the fasted state in continuous 28-day cycles.
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口服胶囊每日一次
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实验性的：Phase 1a Dose Level 4: ZE94-0605 500 mg QD
Participants will receive ZE94-0605 500 mg orally once daily in the fasted state in continuous 28-day cycles.
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口服胶囊每日一次
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实验性的：Phase 1a Dose Level 5: ZE94-0605 650 mg QD
Participants will receive ZE94-0605 650 mg orally once daily in the fasted state in continuous 28-day cycles.
If the maximally tolerated dose or biologically effective dose has not been identified, subsequent dose levels may increase by approximately 33% following Safety Review Committee review.
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口服胶囊每日一次
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实验性的：Phase 1b Expansion Dose A: ZE94-0605 at the MTD
Approximately 15 participants with CCNE1 amplification, or another prospectively specified molecular or cellular feature, will be randomized to receive ZE94-0605 orally once daily at the maximally tolerated dose in the fasted state in continuous 28-day cycles.
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口服胶囊每日一次
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实验性的：Phase 1b Expansion Dose B: ZE94-0605 One Dose Level Below the MTD
Approximately 15 participants with CCNE1 amplification, or another prospectively specified molecular or cellular feature, will be randomized to receive ZE94-0605 orally once daily at one dose level below the maximally tolerated dose in the fasted state in continuous 28-day cycles.
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口服胶囊每日一次
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Number of Participants With Dose-Limiting Toxicities
大体时间：Cycle 1, Day 1 through Day 28
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Number and percentage of participants in Phase 1a who experience a protocol-defined dose-limiting toxicity.
Dose-limiting toxicities are specified hematologic or non-hematologic toxicities graded using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 6.0, that are not primarily attributable to the underlying cancer, a known disease complication, or a comorbid condition.
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Cycle 1, Day 1 through Day 28
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Maximally Tolerated Dose of ZE94-0605
大体时间：Through completion of the Phase 1a dose-escalation portion, estimated up to approximately 24 months
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The maximally tolerated dose is the highest evaluated dose at which no more than 1 of up to 6 participants experiences a dose-limiting toxicity during Cycle 1. Dose-exposure saturation and evidence of an efficacious dose with an acceptable safety margin may also inform termination of dose escalation.
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Through completion of the Phase 1a dose-escalation portion, estimated up to approximately 24 months
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Recommended Phase 2 Dose of ZE94-0605
大体时间：Through completion of the Phase 1b dose-expansion portion, estimated up to approximately 24 months
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The recommended Phase 2 dose will be selected following randomized evaluation of two Phase 1b expansion doses based on integrated safety, tolerability, pharmacokinetic, pharmacodynamic, and preliminary clinical-activity data.
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Through completion of the Phase 1b dose-expansion portion, estimated up to approximately 24 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Number of Participants With Treatment-Emergent Adverse Events
大体时间：From first dose through 30 days after the last dose of ZE94-0605
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Number and percentage of participants with treatment-emergent adverse events, serious adverse events, and adverse events leading to dose modification, treatment discontinuation, or death.
Severity will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events, Version 6.0.
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From first dose through 30 days after the last dose of ZE94-0605
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Overall Response Rate
大体时间：From baseline through Cycle 26 or end of treatment, up to approximately 24 months
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The proportion of evaluable participants whose best overall response is complete response or partial response, assessed using Response Evaluation Criteria in Solid Tumors, Version 1.1, or other disease-appropriate response criteria specified for the participant.
Results will be summarized by tumor type and CCNE1 amplification status.
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From baseline through Cycle 26 or end of treatment, up to approximately 24 months
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Duration of Response
大体时间：From first documented response through study completion, up to approximately 24 months
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Among participants with a complete or partial response, duration of response is the time from the first documented response until documented disease progression or death from any cause, whichever occurs first.
Results will be summarized by CCNE1 amplification status.
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From first documented response through study completion, up to approximately 24 months
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Overall Survival
大体时间：From first dose through long-term follow-up and study completion, up to approximately 24 months
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Overall survival is the time from the first dose of ZE94-0605 until death from any cause.
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From first dose through long-term follow-up and study completion, up to approximately 24 months
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Maximum Observed Plasma Concentration of ZE94-0605
大体时间：Cycle 1 Day 1 through Cycle 2 Day 2; each cycle is 28 days
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Maximum observed plasma concentration (Cmax) of ZE94-0605 derived from serial plasma pharmacokinetic samples.
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Cycle 1 Day 1 through Cycle 2 Day 2; each cycle is 28 days
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Area Under the Plasma Concentration-Time Curve of ZE94-0605
大体时间：Cycle 1 Day 1 through Cycle 2 Day 2; each cycle is 28 days
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Area under the plasma concentration-time curve (AUC) of ZE94-0605 derived from serial plasma pharmacokinetic samples.
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Cycle 1 Day 1 through Cycle 2 Day 2; each cycle is 28 days
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Time to Maximum Observed Plasma Concentration of ZE94-0605
大体时间：Cycle 1 Day 1 through Cycle 2 Day 2; each cycle is 28 days
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Time to maximum observed plasma concentration (Tmax) of ZE94-0605 derived from serial plasma pharmacokinetic samples.
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Cycle 1 Day 1 through Cycle 2 Day 2; each cycle is 28 days
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Terminal Elimination Half-Life of ZE94-0605
大体时间：Cycle 1 Day 1 through Cycle 2 Day 2; each cycle is 28 days
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Apparent terminal elimination half-life of ZE94-0605 derived from serial plasma pharmacokinetic samples.
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Cycle 1 Day 1 through Cycle 2 Day 2; each cycle is 28 days
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Change From Baseline in Serum Thymidine Kinase 1
大体时间：Cycle 1 Day 1 through Cycle 2 Day 2, including additional predose assessments on Cycle 1 Days 8 and 15
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Serum thymidine kinase 1 concentrations and change from baseline will be evaluated as a pharmacodynamic marker of ZE94-0605 activity.
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Cycle 1 Day 1 through Cycle 2 Day 2, including additional predose assessments on Cycle 1 Days 8 and 15
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Change in Plasma Circulating Tumor DNA
大体时间：Predose on Day 1 of Cycles 1, 2, 3, and 6; at scheduled response assessments; and at end of treatment, relapse, or progression
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Plasma circulating tumor DNA will be evaluated by research next-generation sequencing to assess molecular response dynamics and potential mechanisms of resistance.
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Predose on Day 1 of Cycles 1, 2, 3, and 6; at scheduled response assessments; and at end of treatment, relapse, or progression
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Change From Baseline in Exploratory Biomarkers of CDK2 Inhibition
大体时间：Cycle 1 Day 1 predose, 2 hours, 8 hours, and approximately 24 hours postdose
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Alternative exploratory biomarkers of CDK2 pathway inhibition may be evaluated ex vivo using plasma samples to refine and validate surrogate measures of target activity.
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Cycle 1 Day 1 predose, 2 hours, 8 hours, and approximately 24 hours postdose
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Association of Tumor Molecular Characteristics With Response or Resistance
大体时间：From baseline tissue collection through disease progression, up to approximately 24 months
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Archived or newly obtained tumor tissue may be evaluated by next-generation sequencing and other exploratory analyses to assess molecular features associated with response to, or resistance to, ZE94-0605 and to support potential companion-diagnostic development.
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From baseline tissue collection through disease progression, up to approximately 24 months
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2026年6月25日
初级完成 (估计的)
2028年1月1日
研究完成 (估计的)
2028年5月1日
研究注册日期
首次提交
2026年3月27日
首先提交符合 QC 标准的
2026年4月6日
首次发布 (实际的)
2026年4月13日
研究记录更新
最后更新发布 (实际的)
2026年7月29日
上次提交的符合 QC 标准的更新
2026年7月28日
最后验证
2026年7月1日
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- ZE94-0605-0001
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
不
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.