Study of [177Lu]Lu-DWJ155 and [68Ga]Ga-DWJ155 in Patients With Solid Tumors
A Phase I Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [177Lu]Lu-DWJ155 and Safety and Imaging Properties of [68Ga]Ga-DWJ155 in Patients With Solid Tumors
研究概览
地位
详细说明
The study will be done in two parts. The first part is called "escalation" and the second part is called "expansion". In both parts of the study, patients will initially be imaged with a [68Ga]Ga-DWJ155 positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan. In the escalation part, different doses of [177Lu]Lu-DWJ155 will then be tested to identify recommended dose(s) (RD(s)) for further evaluation. The expansion part of the study will examine the safety and preliminary efficacy of [177Lu]Lu-DWJ155 at the RD(s) determined during the escalation part.
In both parts, there will be a safety follow-up period after the last [177Lu]Lu-DWJ155 administration.
研究类型
注册 (估计的)
阶段
- 阶段1
联系人和位置
学习联系方式
- 姓名:Novartis Pharmaceuticals
- 电话号码:1-888-669-6682
- 邮箱:novartis.email@novartis.com
研究联系人备份
- 姓名:Novartis Pharmaceuticals
- 电话号码:+41613241111
学习地点
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Quebec
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Montreal、Quebec、加拿大、H4A 3J1
- 招聘中
- Novartis Investigative Site
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Montreal、Quebec、加拿大、H2X 0A9
- 招聘中
- Novartis Investigative Site
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Chiba
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Kashiwa、Chiba、日本、2778577
- 招聘中
- Novartis Investigative Site
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New South Wales
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Darlinghurst、New South Wales、澳大利亚、2010
- 招聘中
- Novartis Investigative Site
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Nebraska
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Omaha、Nebraska、美国、68130
- 招聘中
- Nebraska Cancer Specialists
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首席研究员:
- Ralph Hauke
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接触:
- Marlene Bridwell
- 电话号码:+1 402 691 6972
- 邮箱:mbridwell@nebraskacancer.com
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Male or female patients age ≥ 18 years.
- Patients with one of the following histologically or cytologically confirmed and documented malignancies who have progressed on or been intolerant to standard of care therapy, and are not considered appropriate for any standard therapy with proven benefit, in the investigator's judgment:
Dose Escalation:
- Advanced HER2+ breast cancer with disease progression after at least two prior lines of systemic therapy in the advanced setting
- Advanced HR+/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
- Advanced NSCLC without actionable genetic alterations (AGAs) with disease progression after prior therapy in the advanced setting
- Advanced NSCLC with AGAs who have received prior treatment
- Measurable disease as determined by RECIST version 1.1.
Dose Expansion:
- Advanced HER2+ breast cancer with disease progression after at least two prior lines of systemic therapy in the advanced setting
- Advanced HR+/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
- Advanced HR+/HER2 0 breast cancer with disease progression after prior therapy in the advanced setting
- Advanced HR-/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
- Advanced HR-/HER2 0 breast cancer with disease progression after prior therapy in the advanced setting
- Advanced NSCLC with AGAs, who have received prior treatment
- Advanced NSCLC without known AGAs who have received prior treatment.
- Advanced gastric/GEJ cancer with HER2 IHC 3+ or 2+ (ISH + or -), following disease progression after prior therapy in the advanced setting
- Advanced bladder cancer following disease progression after prior therapy in the advanced setting
- Measurable disease as determined by RECIST version 1.1.
Exclusion Criteria:
Out-of-range laboratory values defined as:
- Creatinine clearance < 60 mL/min (calculated using CKD-EPI 2021 formula, or measured)
- Total bilirubin > 1.5 x ULN (except for patients with Gilbert's syndrome who are excluded if total bilirubin >3.0 x ULN) or direct bilirubin > 1.5 x ULN
- Alanine aminotransferase (ALT) > 3 x ULN, except for patients with tumor involvement of the liver who are excluded if ALT > 5 x ULN
- Aspartate aminotransferase (AST) > 3 x ULN, except for patients with tumor involvement of the liver who are excluded if AST > 5 x ULN
- Lipase > 1.5 x ULN
- Absolute neutrophil count (ANC) < 1.5 x 109/L
- Hemoglobin < 9 g/dL
- Platelet count < 100 x 109/L
- Initiation of hematopoietic colony stimulating factors, thrombopoietin mimetics, or erythroid stimulating agents initiated ≤ 2 weeks prior to imaging agent administration.
- Use of transfusion support ≤4 weeks prior to imaging agent administration.
- Impaired cardiac function or clinically significant cardiac disease.
- Unmanageable urinary tract obstruction or urinary incontinence.
- Any serious uncontrolled infection (acute or chronic).
- Pregnant or breastfeeding women.
Treatment with any of the following anti-cancer therapies prior to imaging agent administration within the stated timeframes:
- Prior treatment with any therapeutic radiopharmaceutical
- < 10 half-lives for any imaging radiopharmaceutical
- ≤ 4 weeks for external beam radiation therapy (EBRT) or brachytherapy
- ≤ 6 months for lung-directed external beam radiotherapy
- Patients with non-tumor uptake of [68Ga]Ga-DWJ155 in tissues or organs that, in the opinion of the investigator, increases the risk associated with [177Lu]Lu-DWJ155 treatment.
Other protocol-defined inclusion/exclusion criteria may apply.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 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:Dose Escalation
Patients will receive [68Ga]Ga-DWJ155 and, if eligible, [177Lu]Lu-DWJ155.
In this part, multiple dose levels of [177Lu]Lu-DWJ155 will be evaluated.
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Radioligand imaging agent
其他名称:
Radioligand therapy
其他名称:
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实验性的:Dose Expansion
Patients will receive [68Ga]Ga-DWJ155 and, if eligible, [177Lu]Lu-DWJ155 at the recommended dose established during the dose escalation part.
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Radioligand imaging agent
其他名称:
Radioligand therapy
其他名称:
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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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Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) of [177Lu]Lu-DWJ155
大体时间:Up to approximately 53 months
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Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, echocardiograms (ECGs), and imaging assessments qualifying and reported as AEs.
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Up to approximately 53 months
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Incidence of dose-limiting toxicities (DLTs) of [177Lu]Lu-DWJ155
大体时间:Up to 6 weeks
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A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness/injury or concomitant medications that occurs within the first treatment cycle.
Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
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Up to 6 weeks
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Frequency of dose interruptions and reductions [177Lu]Lu-DWJ155
大体时间:11 months
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Number of participants with dose interruptions and/or reductions to assess the tolerability.
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11 months
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Dose intensity [177Lu]Lu-DWJ155
大体时间:11 months
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Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure
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11 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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Overall Response Rate (ORR) per RECIST v1.1
大体时间:Up to approximately 53 months
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ORR is defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) as per local review and according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
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Up to approximately 53 months
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Disease Control Rate (DCR) per RECIST v1.1
大体时间:Up to approximately 53 months
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DCR is defined as the proportion of patients with a BOR of CR, PR, or stable disease (SD) as per local review and according to RECIST v1.1.
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Up to approximately 53 months
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Duration of Response (DOR) per RECIST v1.1
大体时间:Up to approximately 53 months
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DOR is the time between the first documented response (CR or PR) and the date of progression as per local review and according to RECIST v1.1, or death due to any cause.
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Up to approximately 53 months
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Progression-Free Survival (PFS) per RECIST v1.1
大体时间:Up to approximately 53 months
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PFS is defined as the time from the date of start of treatment to the date of the first documented progression as per local review and according to RECIST v1.1 or death due to any cause.
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Up to approximately 53 months
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Area under the concentration-time curve (AUC) of [177Lu]Lu-DWJ155
大体时间:From pre-dose up to 168 hours after the end of the infusion on Day 1
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The pharmacokinetic (PK) analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units.
AUC will be determined by non-compartmental methods.
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From pre-dose up to 168 hours after the end of the infusion on Day 1
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Systemic clearance (CL) of [177Lu]Lu-DWJ155
大体时间:From pre-dose up to 168 hours after the end of the infusion on Day 1
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The PK analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units.
CL will be determined by non-compartmental methods.
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From pre-dose up to 168 hours after the end of the infusion on Day 1
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Maximum observed concentration (Cmax) of [177Lu]Lu-DWJ155
大体时间:From pre-dose up to 168 hours after the end of the infusion on Day 1
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The PK analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units.
Cmax will be determined by non-compartmental methods.
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From pre-dose up to 168 hours after the end of the infusion on Day 1
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Volume of distribution during the terminal phase (Vz) of [177Lu]Lu-DWJ155
大体时间:From pre-dose up to 168 hours after the end of the infusion on Day 1
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The PK analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units.
Vz will be determined by non-compartmental methods.
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From pre-dose up to 168 hours after the end of the infusion on Day 1
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Terminal half-life (T1/2) of [177Lu]Lu-DWJ155
大体时间:From pre-dose up to 168 hours after the end of the infusion on Day 1
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The PK analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units.
T1/2 will be determined by non-compartmental methods.
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From pre-dose up to 168 hours after the end of the infusion on Day 1
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Urinary excretion of [177Lu]Lu-DWJ155
大体时间:From pre-dose up to 72 hours after the end of the infusion on Day 1
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The PK analysis will be performed based on decay-corrected urine radioactivity concentration data converted to mass units.
Urinary excretion will be derived based on the percentage of injected dose excreted in urine in each collection interval and overall.
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From pre-dose up to 72 hours after the end of the infusion on Day 1
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Renal clearance (CLr) of [177Lu]Lu-DWJ155
大体时间:From pre-dose up to 72 hours after the end of the infusion on Day 1
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The PK analysis will be performed based on decay-corrected blood and urine radioactivity concentration data converted to mass units.
CLr will be determined by non-compartmental methods.
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From pre-dose up to 72 hours after the end of the infusion on Day 1
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Absorbed radiation dose in selected organs, tumor lesions and total body of [177Lu]Lu-DWJ155
大体时间:Up to 168 hours after the end of the infusion on Day 1
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Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) images will be acquired to assess total body, organ and tumor lesion dosimetry.
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Up to 168 hours after the end of the infusion on Day 1
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Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) of [68Ga]Ga-DWJ155:
大体时间:Up to 3 days
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Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, echocardiograms (ECGs), and cardiac imaging qualifying and reported as AEs.
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Up to 3 days
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Standard uptake values (SUVs) in normal tissues and selected tumor lesions of [68Ga]Ga-DWJ155
大体时间:Up to approximately 1.5 hours after the end of infusion
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68Ga-DWJ155 positron emission tomography/computed tomography (PET/CT) or positron emission tomography/magnetic resonance imaging (PET/MRI) imaging assessments will be performed to derive SUVs in normal tissues and selected tumor lesions.
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Up to approximately 1.5 hours after the end of infusion
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
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
- CFML539A12101
- 2024-518348-19 (其他标识符:EU CTIS)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
IPD 计划说明
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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