NCT05187624已完成1 期
An Open-label, Multicenter, Phase I Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Activity of RO7428731 in Participants With Glioblastoma Expressing Mutant Epidermal Growth Factor Receptor Variant III
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 8
- 主要终点
- Percentage of Participants with Adverse Events (AEs)
研究概览
简要总结
This is an open-label, multicenter study to assess safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and preliminary efficacy of RO7428731 administered as a monotherapy in participants with newly diagnosed or recurrent epidermal growth factor receptor variant III (EGFRvIII)-positive glioblastoma (GBM).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Inclusion criteria for all participants:
- •Life expectancy of greater than or equal to 12 weeks, in the opinion of the Investigator
- •Diagnosis of GBM based on World Health Organization (WHO) classification of central nervous system (CNS) tumors, 5th edition
- •Participants must have confirmed EGFRvIII-expression
- •Karnofsky Performance Status (KPS) Score of >=70%
- •Adequate organ functions prior to start of study treatment
- •Willingness to abide by contraceptive measures for the duration of the study.
- •Inclusion criteria for Part I and Part II only:
- •Participants whose tumors have an unmethylated (Part I and Part II) or methylated (Part I only) O6-methylguanine-DNA methyltransferase (MGMT) promotor status based on local assessment
- •Participants (in Part I): Adult participants with newly diagnosed EGFRvIII-positive GBM with unmethylated MGMT promotor status who have completed standard of care therapy with surgical resection and adjuvant radiotherapy with or without concomitant temozolomide. Participants are allowed to have received any number of cycles of temozolomide maintenance. Adult participants with newly diagnosed EGFRvIII-positive GBM with methylated MGMT promotor status who have completed standard of care with surgical resection and adjuvant radiotherapy with concomitant and maintenance temozolomide or discontinued temozolomide maintenance due to reasons other than progressive disease.
- •Participants (in Part II): Adult participants with newly diagnosed EGFRvIII-positive GBM with unmethylated MGMT promotor status who have completed standard of care therapy with surgical resection and adjuvant radiotherapy with or without concomitant temozolomide.
- •Inclusion criteria for Part III and Part IV A only:
- •Documented first or second recurrence of GBM
- •At least one measurable GBM lesion as per Response Assessment in Neuro-Oncology (RANO) criteria prior to initiation of study treatment.
排除标准
- •Exclusion criteria for all participants:
- •Participants with infratentorial tumors and tumors primarily located in or close to critical structures (e.g., brain stem)
- •Presence of extracranial metastatic or leptomeningeal disease
- •Known hypersensitivity to immunoglobulins or to any other component of the investigational medicinal product formulation
- •Active bleeding or pathological condition that carries a high risk of bleeding, including inherited and acquired coagulopathies
- •Participants unable to undergo an MRI with contrast.
- •Exclusion criteria for Part I and Part II only:
- •Recurrent malignant gliomas
- •Any prior anti-tumor treatment for GBM: tumor resection, adjuvant radiotherapy with or without concomitant temozolomide and temozolomide maintenance (Part I only) must be the only tumor-directed treatment that the participant has received for GBM.
- •Exclusion criteria for Part III and Part IV A only:
- •More than two recurrences of GBM
- •Prior anti-EGFRvIII-targeting agents (including vaccines), anti-angiogenic therapy, and/or gene therapy for the treatment of GBM and gliomas.
研究组 & 干预措施
Part I: Dose Escalation
Experimental
Participants with newly diagnosed GBM will receive RO7428731, intravenously (IV), up to one year or until disease progression, withdrawal of consent, unacceptable toxicity, or death, whichever occurs first.
干预措施: RO7428731 (Drug)
Part II: Dose-Expansion(s)
Experimental
Participants with newly diagnosed GBM will receive RO7428731, IV, in maximum of two dose expansion cohorts at a dose(s) not exceeding the maximum tolerated dose (MTD) established in Part I.
干预措施: RO7428731 (Drug)
Part III: Safety Run-in
Experimental
Participants with recurrent GBM will receive RO7428731, IV in a dosing schedule determined in Part I. At the end of the Safety Run-in period, a decision will be made as to whether to open the Dose-Expansion Cohort Part IVA or open a second Safety Run-in Cohort at a lower dose.
干预措施: RO7428731 (Drug)
Part IV A: Dose-Expansions Cohort
Experimental
Participants with recurrent GBM will receive RO7428731, IV at specified doses and dosing schedules.
干预措施: RO7428731 (Drug)
结局指标
主要结局
Percentage of Participants with Adverse Events (AEs)
时间窗: Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months)
Percentage of Participants with Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (each cycle is 21 days)
次要结局
- Disease Control Rate (DCR)(From start of study treatment up to approximately 3 years)
- Duration of Response (DOR)(From the time of first occurrence of a documented response until the time of documented disease progression or death (death within 30 days from last study treatment) from any cause, whichever occurs first (up to approximately 3 years))
- Progression-free Survival (PFS)(From start of study treatment to the first occurrence of documented disease progression or death from any cause, whichever occurs first (up to approximately 3 years))
- Overall Survival (OS)(From start of study treatment to the time of death from any cause (up to approximately 3 years))
- Objective Response Rate (ORR)(From start of study treatment up to approximately 3 years)
- Serum Concentration of RO7428731(Up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months))
- Percentage of Participants With RO7428731 Anti-drug Antibodies (ADAs)(From baseline up to the safety follow-up visit 60 days after the last treatment (up to approximately 15 months))
研究者
研究点 (8)
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