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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 156
- 试验地点
- 6
- 主要终点
- Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) of [177Lu]Lu-DWJ155
研究概览
简要总结
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.
详细描述
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: [177Lu]Lu-DWJ155 (Drug)
Dose Expansion
Patients will receive [68Ga]Ga-DWJ155 and, if eligible, [177Lu]Lu-DWJ155 at the recommended dose established during the dose escalation part.
干预措施: [68Ga]Ga-DWJ155 (Diagnostic Test)
Dose Expansion
Patients will receive [68Ga]Ga-DWJ155 and, if eligible, [177Lu]Lu-DWJ155 at the recommended dose established during the dose escalation part.
干预措施: [177Lu]Lu-DWJ155 (Drug)
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.
干预措施: [68Ga]Ga-DWJ155 (Diagnostic Test)
结局指标
主要结局
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) of [177Lu]Lu-DWJ155
时间窗: 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.
Incidence of dose-limiting toxicities (DLTs) of [177Lu]Lu-DWJ155
时间窗: 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.
Frequency of dose interruptions and reductions [177Lu]Lu-DWJ155
时间窗: 11 months
Number of participants with dose interruptions and/or reductions to assess the tolerability.
Dose intensity [177Lu]Lu-DWJ155
时间窗: 11 months
Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure
次要结局
- Overall Response Rate (ORR) per RECIST v1.1(Up to approximately 53 months)
- Disease Control Rate (DCR) per RECIST v1.1(Up to approximately 53 months)
- Duration of Response (DOR) per RECIST v1.1(Up to approximately 53 months)
- Progression-Free Survival (PFS) per RECIST v1.1(Up to approximately 53 months)
- Area under the concentration-time curve (AUC) of [177Lu]Lu-DWJ155(From pre-dose up to 168 hours after the end of the infusion on Day 1)
- Systemic clearance (CL) of [177Lu]Lu-DWJ155(From pre-dose up to 168 hours after the end of the infusion on Day 1)
- Maximum observed concentration (Cmax) of [177Lu]Lu-DWJ155(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(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(From pre-dose up to 168 hours after the end of the infusion on Day 1)
- Urinary excretion of [177Lu]Lu-DWJ155(From pre-dose up to 72 hours after the end of the infusion on Day 1)
- Renal clearance (CLr) of [177Lu]Lu-DWJ155(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(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:(Up to 3 days)
- Standard uptake values (SUVs) in normal tissues and selected tumor lesions of [68Ga]Ga-DWJ155(Up to approximately 1.5 hours after the end of infusion)