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A Study of Zedoresertib (Debio 0123) in Combination With Temozolomide in Adult Participants With Recurrent or Progressive Glioblastoma and of Zedoresertib (Debio 0123) in Combination With Temozolomide and Radiotherapy in Adult Participants With Newly Diagnosed Glioblastoma

2026年10月26日 更新者：Debiopharm International SA

Debio 0123 联合替莫唑胺治疗复发性或进展性胶质母细胞瘤成人参与者以及 Debio 0123 联合替莫唑胺和放疗治疗新诊断胶质母细胞瘤成人参与者的 1/2 期开放标签研究

The primary purpose of the Phase 1 (Dose Escalation) of this study is to identify the dose-limiting toxicities (DLTs) of zedoresertib combined with temozolomide (TMZ) (Arm A) and with TMZ and radiotherapy (RT) (Arms B and C) and to characterize the safety and tolerability of these combinations in adult participants with glioblastoma (GBM). Arm B which was previously added to the protocol, has been permanently halted per the safety monitoring committees' decision on the safety findings of this arm.

The primary purpose of Phase 1 (Dose expansion) of the study is to assess the doses studied under Phase 1 (Dose Escalation) Arm A and identify the recommended dose (RD) for further development.

The Phase 2 will start once the RD Phase 1 has been defined. The primary objective of Phase 2 is to assess the efficacy of zedoresertib at the RD for further development in combination with TMZ, compared to the standard of care (SOC) in adult participants with GBM.

研究概览

地位

招聘中

条件

干预/治疗

研究类型

介入性

注册 (估计的)

116

阶段

  • 阶段2
  • 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

学习地点

  • 瑞士
      • Zurich、瑞士、CH-8091
        • 招聘中
        • Universitaetsspital Zuerich
  • 美国
    • Illinois
      • Chicago、Illinois、美国、60611
        • 招聘中
        • Northwestern Memorial Hospital
    • New York
      • New York、New York、美国、10016
        • 招聘中
        • New York University Langone Medical Center
      • New York、New York、美国、10021
        • 招聘中
        • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
    • Texas
      • Dallas、Texas、美国、75246
        • 招聘中
        • Baylor Scott & White Research Institute
      • Houston、Texas、美国、77030
        • 招聘中
        • The University of Texas MD Anderson Cancer Center
      • San Antonio、Texas、美国、78229
        • 招聘中
        • South Texas Accelerated Research Therapeutics (START)
    • Utah
      • Salt Lake City、Utah、美国、84112
        • 招聘中
        • Huntsman Cancer Institute
    • Washington
      • Seattle、Washington、美国、98109
        • 招聘中
        • Fred Hutchinson Cancer Research Center
  • 西班牙
      • Barcelona、西班牙、08035
        • 招聘中
        • Hospital Universitario Vall d'Hebron
      • Donostia / San Sebastian、西班牙、20014
        • 招聘中
        • Hospital Universitario Donostia
      • Madrid、西班牙、28041
        • 招聘中
        • Hospital Universitario 12 de Octubre
      • Madrid、西班牙、28040
        • 招聘中
        • South Texas Accelerated Research Therapeutics (START)
      • Madrid、西班牙、28027
        • 招聘中
        • Clinica Universidad de Navarra (CUN)
      • Pamplona、西班牙、31008
        • 招聘中
        • Clinica Universidad de Navarra (CUN)
      • Valencia、西班牙、46010
        • 招聘中
        • Hospital Clinico Universitario de Valencia

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

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Screening Inclusion Criteria for Phase 1 and Phase 2:

  • Signed written informed consent approved before undertaking any study-specific procedures.
  • Age ≥18 years of age.
  • Willing to provide archived or fresh tumor sample, if available. Receipt of tumor sample is not required for the start of study treatment.
  • Adequate bone marrow, hepatic, and renal function.
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  • Willing to practice highly effective methods of contraception.
  • Life expectancy of at least 3 months in the best judgment of the Investigator.
  • Measurable or non-measurable disease as per RANO criteria by gadolinium (Gd)-based contrast-enhanced brain magnetic resonance imaging (MRI).
  • Participants receiving corticosteroids must be on a stable or decreasing dose of ≤4 mg daily dexamethasone (or ≤25 mg prednisone) for the 7 days prior to the start of study treatment.
  • Participants with seizures must be adequately controlled on a stable regimen of anti-epileptic drugs.

Additional specific inclusion criteria for Phase 1 and Phase 2:

• A maximum of 1 [for Phase 1 (Dose Expansion) and phase 2] or 2 (Phase 1 Arm A) prior treatment lines of which first-line must be treatment with TMZ-based chemoradiotherapy (TMZ concomitantly with RT).

Note: Only 1 prior line of systemic therapy is allowed; combination therapy with TMZ and RT with or without subsequent TMZ maintenance treatment is considered as 1 systemic line. Prior surgery, radiation, or localized delivery of therapeutic agents (i.e., carmustine-containing wafers [GLIADEL®]) for first recurrence is allowed.

  • Documented disease recurrence or progression by diagnostic biopsy or Gd-based contrast-enhanced brain MRI as per RANO criteria.
  • KPS ≥60.

Additional specific inclusion criteria for Phase 1 Arm A:

  • Participants must have one of the following histopathologically proven diagnoses (WHO 2021):
  • GBM Isocitrate dehydrogenase (IDH)-wildtype Grade 4 which may include secondary GBMs (i.e., those that progress from low-grade gliomas).
  • Astrocytoma, IDH-mutant, Grade 3

Additional specific inclusion criteria for Phase 1 Arm B and C:

  • Participants must have a new, histopathologically proven diagnosis of GBM, IDH-wildtype, Grade 4 (based on WHO 2021), which may include secondary GBMs (i.e., those that progress from low-grade gliomas) if the prior treatment included surgery only.
  • KPS ≥70.

Additional specific inclusion criteria for Phase 1 dose expansion and Phase 2:

• Participants must have a histopathologically proven diagnosis of GBM, IDH-wildtype Grade 4 WHO 2021

Additional specific exclusion criteria for Phase 1 Arm A • Prior treatment with more than 2 lines of therapy for GBM, IDH-wildtype, Grade 4, or for astrocytoma, IDH-mutant, Grade 3

Additional specific exclusion criteria for Phase 1 and Phase 2

  • Known contraindication to undergoing for Gd-based, contrast-enhanced MRI.
  • Any anticancer treatment, monoclonal antibodies/biologics, investigational treatment, or RT with curative intent within 28 days prior to starting study treatment.
  • Hypersensitivity to zedoresertib, TMZ, dacarbazine, or any of the excipients found in the formulation for zedoresertib or TMZ.
  • Prior exposure to any WEE1 inhibitor.
  • History of other malignancies requiring active treatment in the last 2 years prior to the first dose of study treatment except for superficial bladder cancers, adequately treated low-risk prostate cancer under active surveillance, ductal carcinoma in situ or other carcinomas in situ, and non-melanoma skin cancers (basal cell/squamous cell skin cancer) that have been treated with curative intent.
  • Left ventricular ejection fraction (LVEF) below 55%.

Additional specific exclusion criteria for Phase 1 Arm B and C:

  • Prior radiation, chemotherapy, biological therapy, interstitial brachytherapy, implanted chemotherapy, therapeutics delivered by local injection or convection-enhanced delivery for GBM.
  • Prior therapy that would result in an overlap of the radiation fields.

Additional specific exclusion criteria for Phase 1 dose expansion and Phase 2

• Prior treatment with more than 1 line of systemic therapy for GBM, IDH-wildtype, Grade 4 (based on WHO 2021). Combination therapy with TMZ and RT with or without subsequent TMZ maintenance treatment is considered as 1 systemic line.

[Note: Other inclusion/exclusion criteria mentioned in the protocol may apply.]

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：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Phase 1 (Dose Escalation): Arm A - Zedoresertib + Temozolomide

Participants will receive intermittent zedoresertib, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years.
药品：Zedoresertib

Administered as capsules.

其他名称：
  • Debio 0123
药品：Temozolomide

Administered as capsules.
实验性的：Phase 1 (Dose Escalation): Arm B - Zedoresertib + Temozolomide + Radiotherapy

Participants will receive intermittent zedoresertib, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks. As per Protocol _V4.0 Arm B has been permanently halted.
药品：Zedoresertib

Administered as capsules.

其他名称：
  • Debio 0123
药品：Temozolomide

Administered as capsules.

辐射：Radiotherapy

Administered in accordance with the local clinical practice and applicable Radiation Therapy Oncology Group (RTOG) or the European Organization for Research and Treatment of Cancer (EORTC) guidelines.
实验性的：Phase 1 (Dose Escalation): Arm C - Zedoresertib + Temozolomide + Radiotherapy

Participants will receive intermittent zedoresertib, escalating doses along with TMZ and concomitant administration of radiotherapy (RT) for up to 6 weeks.
药品：Zedoresertib

Administered as capsules.

其他名称：
  • Debio 0123
药品：Temozolomide

Administered as capsules.

辐射：Radiotherapy

Administered in accordance with the local clinical practice and applicable Radiation Therapy Oncology Group (RTOG) or the European Organization for Research and Treatment of Cancer (EORTC) guidelines.
实验性的：Phase 1 (Dose Expansion): Zedoresertib + Temozolomide

Participants will receive zedoresertib, escalating doses along with temozolomide (TMZ) in each 28-day cycle for up to 2 years. Participants will receive one of the 2 selected doses for further investigation.
药品：Zedoresertib

Administered as capsules.

其他名称：
  • Debio 0123
药品：Temozolomide

Administered as capsules.
实验性的：Phase 2: Zedoresertib RD + Temozolomide

Participants will receive intermittent zedoresertib RD along with TMZ in each 28-day cycle for up to 2 years.
药品：Zedoresertib

Administered as capsules.

其他名称：
  • Debio 0123
药品：Temozolomide

Administered as capsules.

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
第 1 阶段（剂量递增）：经历剂量限制性毒性 (DLT) 的参与者数量
大体时间：第 1 阶段：A 组：周期 1（周期 = 28 天）； B 组和 C 组：最长约 1.8 个月
第 1 阶段：A 组：周期 1（周期 = 28 天）； B 组和 C 组：最长约 1.8 个月
第 1 阶段（剂量递增）：至少发生一种治疗引起的不良事件 (TEAE) 的参与者人数
大体时间：治疗结束后最长 30 天（A 组：最长约 26 个月，B 组和 C 组：最长约 3.5 个月）
治疗结束后最长 30 天（A 组：最长约 26 个月，B 组和 C 组：最长约 3.5 个月）
第 1 阶段（剂量递增）：实验室、生命体征、心电图 (ECG) 和超声心动图 (ECHO) 参数出现临床显着异常的参与者数量
大体时间：治疗结束后最长 30 天（A 组：最长约 26 个月，B 组和 C 组：最长约 3.5 个月）
治疗结束后最长 30 天（A 组：最长约 26 个月，B 组和 C 组：最长约 3.5 个月）
第 1 阶段（剂量扩展）：至少发生一种治疗引起的不良事件 (TEAE) 的参与者人数
大体时间：最长约 26 个月
最长约 26 个月
第 1 阶段（剂量扩展）：根据神经肿瘤学反应评估 (RANO) 标准，通过客观反应 (OR) 评估肿瘤大小相对于基线的变化
大体时间：从研究治疗开始直至疾病进展或研究结束（最长约 66 个月）
从研究治疗开始直至疾病进展或研究结束（最长约 66 个月）
第 1 阶段（剂量扩展）：药效学 PDy，磷酸化细胞分裂周期 (pCDC2) 相对于基线的变化
大体时间：第 1 周期第 10 天的给药前和给药后 4 至 6 小时（周期 = 28 天）
第 1 周期第 10 天的给药前和给药后 4 至 6 小时（周期 = 28 天）
第 2 阶段：总体生存期 (OS)
大体时间：从研究治疗开始直至因任何原因死亡或研究结束（最长约 66 个月）
从研究治疗开始直至因任何原因死亡或研究结束（最长约 66 个月）
Phase 1 (Dose Escalation): Change From Baseline in Karnofsky Performance Status (KPS) Score
大体时间：Until disease progression or end of study (approximately 66 months)

KPS is an assessment tool for functional impairment. It is a standard way of measuring the ability of participants with cancer to perform ordinary tasks. The KPS scores range from 0 (death) to 100 (no evidence of disease). A higher score means the participant is better able to carry out daily activities.
Until disease progression or end of study (approximately 66 months)
Phase 1 (Dose Expansion): Plasma Concentration of Zedoresertib and its Metabolite
大体时间：Predose and at multiple timepoints up to 6 hours post dose up to Day 15 of Cycle 1 (Cycle=28 days)
Predose and at multiple timepoints up to 6 hours post dose up to Day 15 of Cycle 1 (Cycle=28 days)

次要结果测量

结果测量
措施说明
大体时间
第 2 阶段：至少有一个 TEAE 的参与者人数
大体时间：治疗结束后最多 30 天（最多约 26 个月）
治疗结束后最多 30 天（最多约 26 个月）
第 2 阶段：在实验室、生命体征和 ECG 参数方面具有临床显着异常的参与者人数
大体时间：治疗结束后最多 30 天（最多约 26 个月）
治疗结束后最多 30 天（最多约 26 个月）
第 1 阶段（剂量扩展）：OS
大体时间：从研究治疗开始直至因任何原因死亡或研究结束（最长约 66 个月）
从研究治疗开始直至因任何原因死亡或研究结束（最长约 66 个月）
第 1 阶段（剂量扩展）：实验室、生命体征、心电图和（ECHO 参数）出现临床显着异常的参与者人数
大体时间：治疗结束后最多 30 天（最多约 26 个月）
治疗结束后最多 30 天（最多约 26 个月）
第 1 阶段（剂量扩展）：至少接受过一次 TEAE 的参与者人数
大体时间：治疗结束后最多 30 天（最多约 26 个月）
治疗结束后最多 30 天（最多约 26 个月）
第 1 阶段和第 2 阶段：根据神经肿瘤学 (RANO) 标准中的反应评估获得最佳总体反应 (BOR) 的参与者的百分比
大体时间：从研究治疗开始直至疾病进展或研究结束（最长约 66 个月）
从研究治疗开始直至疾病进展或研究结束（最长约 66 个月）
第 1 阶段和第 2 阶段：根据 RANO 标准评估具有客观反应 (OR) 的参与者的百分比
大体时间：直至学习结束（约 66 个月）
直至学习结束（约 66 个月）
第 1 阶段和第 2 阶段：根据 RANO 标准评估的疾病控制 (DC) 参与者的百分比
大体时间：从研究治疗开始直至疾病进展或研究结束（最长约 66 个月）
从研究治疗开始直至疾病进展或研究结束（最长约 66 个月）
第 1 阶段和第 2 阶段：根据 RANO 标准评估响应持续时间 (DOR)
大体时间：直至疾病进展或研究结束（最长约 66 个月）
直至疾病进展或研究结束（最长约 66 个月）
第 1 阶段和第 2 阶段：根据 RANO 标准评估无进展生存期 (PFS)
大体时间：从研究治疗开始直至疾病进展或死亡或研究结束（最长约 66 个月）
从研究治疗开始直至疾病进展或死亡或研究结束（最长约 66 个月）
Phase 1 (Dose Escalation): Plasma Concentration of Temozolomide
大体时间：Phase 1: Predose and at multiple timepoints up to 7 hours post dose up to Day 5 of Cycle 1 (Arm A) and up to Day 29 (Arm B and C)

The PK of temozolomide will be evaluated in plasma.
Phase 1: Predose and at multiple timepoints up to 7 hours post dose up to Day 5 of Cycle 1 (Arm A) and up to Day 29 (Arm B and C)
Phase 1 (Dose Expansion): Change From Baseline in KPS Score
大体时间：Until disease progression or end of study (approximately 66 months)

KPS is an assessment tool for functional impairment. It is a standard way of measuring the ability of participants with cancer to perform ordinary tasks. The KPS scores range from 0 (death) to 100 (no evidence of disease). A higher score means the participant is better able to carry out daily activities.
Until disease progression or end of study (approximately 66 months)
Phase 2: Change From Baseline in KPS Score
大体时间：Until disease progression or end of study (approximately 66 months)

KPS is an assessment tool for functional impairment. It is a standard way of measuring the ability of participants with cancer to perform ordinary tasks. The KPS scores range from 0 (death) to 100 (no evidence of disease). A higher score means the participant is better able to carry out daily activities.
Until disease progression or end of study (approximately 66 months)
Phases 1 and 2: Plasma Concentration of Zedoresertib and its Metabolite
大体时间：Phase1(Dose Escalation):Predose, multiple timepoints upto 8hours postdose upto Day 15 of Cycle 1(Arm A) and upto Day 29(Arms B and C);Phase1(Dose expansion)andPhase2: Predose, multiple timepoints upto 4hours postdose upto Day 15 of Cycle1(Cycle=28 days)

The pharmacokinetics (PK) of zedoresertib and its metabolite will be evaluated in plasma.
Phase1(Dose Escalation):Predose, multiple timepoints upto 8hours postdose upto Day 15 of Cycle 1(Arm A) and upto Day 29(Arms B and C);Phase1(Dose expansion)andPhase2: Predose, multiple timepoints upto 4hours postdose upto Day 15 of Cycle1(Cycle=28 days)

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。

赞助

Debiopharm International SA

调查人员

  • 研究主任：Study Director、Debiopharm International SA

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)

2023年5月15日

初级完成 (估计的)

2028年9月1日

研究完成 (估计的)

2028年9月1日

研究注册日期

首次提交

2023年2月15日

首先提交符合 QC 标准的

2023年3月9日

首次发布 (实际的)

2023年3月13日

研究记录更新

最后更新发布 (实际的)

2026年10月28日

上次提交的符合 QC 标准的更新

2026年10月26日

最后验证

2026年10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

  • Debio 0123-GBM-105
  • 2022-502156-31 (EudraCT编号)
  • U1111-1283-6423 (其他标识符：UTN Number (World Health Organization))

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

是的

研究美国 FDA 监管的设备产品

不

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