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Study of [177Lu]Lu-DWJ155 and [68Ga]Ga-DWJ155 in Patients With Solid Tumors

2026年8月26日 更新者:Novartis Pharmaceuticals

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

The purpose of this phase I study is to evaluate the safety, tolerability, dosimetry, and preliminary anti-tumor activity of [177Lu]Lu-DWJ155 and the safety and imaging properties of [68Ga]Ga-DWJ155 in patients with histologically or cytologically confirmed advanced HER2+, HR+/HER2-negative, or triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), HER2-3+ or 2+ (ISH positive or negative) gastric/gastroesophageal junction (GEJ) cancer, and bladder cancer.

研究概览

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

介入性

注册 (估计的)

156

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

研究联系人备份

  • 姓名:Novartis Pharmaceuticals
  • 电话号码:+41613241111

学习地点

    • Quebec
      • Montreal、Quebec、加拿大、H4A 3J1
        • 招聘中
        • Novartis Investigative Site
      • Montreal、Quebec、加拿大、H2X 0A9
        • 招聘中
        • Novartis Investigative Site
    • Chiba
      • Kashiwa、Chiba、日本、2778577
        • 招聘中
        • Novartis Investigative Site
    • New South Wales
      • Darlinghurst、New South Wales、澳大利亚、2010
        • 招聘中
        • Novartis Investigative Site
    • Nebraska
      • Omaha、Nebraska、美国、68130
        • 招聘中
        • Nebraska Cancer Specialists
        • 首席研究员:
          • Ralph Hauke
        • 接触:

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

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

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: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
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.
Radioligand imaging agent
其他名称:
  • FKL480
Radioligand therapy
其他名称:
  • FML539
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.
Radioligand imaging agent
其他名称:
  • FKL480
Radioligand therapy
其他名称:
  • FML539

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
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
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, echocardiograms (ECGs), and imaging assessments qualifying and reported as AEs.
Up to approximately 53 months
Incidence of dose-limiting toxicities (DLTs) of [177Lu]Lu-DWJ155
大体时间:Up to 6 weeks
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.
Up to 6 weeks
Frequency of dose interruptions and reductions [177Lu]Lu-DWJ155
大体时间:11 months
Number of participants with dose interruptions and/or reductions to assess the tolerability.
11 months
Dose intensity [177Lu]Lu-DWJ155
大体时间:11 months
Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure
11 months

次要结果测量

结果测量
措施说明
大体时间
Overall Response Rate (ORR) per RECIST v1.1
大体时间:Up to approximately 53 months
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).
Up to approximately 53 months
Disease Control Rate (DCR) per RECIST v1.1
大体时间:Up to approximately 53 months
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.
Up to approximately 53 months
Duration of Response (DOR) per RECIST v1.1
大体时间:Up to approximately 53 months
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.
Up to approximately 53 months
Progression-Free Survival (PFS) per RECIST v1.1
大体时间:Up to approximately 53 months
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.
Up to approximately 53 months
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
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.
From pre-dose up to 168 hours after the end of the infusion on Day 1
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
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.
From pre-dose up to 168 hours after the end of the infusion on Day 1
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
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.
From pre-dose up to 168 hours after the end of the infusion on Day 1
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
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.
From pre-dose up to 168 hours after the end of the infusion on Day 1
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
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.
From pre-dose up to 168 hours after the end of the infusion on Day 1
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
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.
From pre-dose up to 72 hours after the end of the infusion on Day 1
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
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.
From pre-dose up to 72 hours after the end of the infusion on Day 1
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
Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) images will be acquired to assess total body, organ and tumor lesion dosimetry.
Up to 168 hours after the end of the infusion on Day 1
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) of [68Ga]Ga-DWJ155:
大体时间:Up to 3 days
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, echocardiograms (ECGs), and cardiac imaging qualifying and reported as AEs.
Up to 3 days
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
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.
Up to approximately 1.5 hours after the end of infusion

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16日

初级完成 (估计的)

2032年5月24日

研究完成 (估计的)

2032年5月24日

研究注册日期

首次提交

2026年6月15日

首先提交符合 QC 标准的

2026年6月15日

首次发布 (实际的)

2026年6月22日

研究记录更新

最后更新发布 (实际的)

2026年8月27日

上次提交的符合 QC 标准的更新

2026年8月26日

最后验证

2026年8月1日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

不

IPD 计划说明

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

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

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.

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