A Phase I, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry and Preliminary Activity of [177Lu]Lu-FF58 in Patients With Selected Advanced Solid Tumors.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Dose intensity for 177Lu-FF58
研究概览
简要总结
The purpose of the study is to test the safety and dosing of [177Lu]Lu-FF58, a radioligand therapy for patients with advanced or metastatic tumors that express proteins known as integrins: alpha-v beta-3 integrin (αvβ3) and alpha-v beta-5 integrin (αvβ5). The study will also further characterize the radioligand imaging agent [68Ga]Ga-FF58 including its ability to identify tumor lesions and its safety profile.
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 be screened with a [68Ga]Ga-FF58 positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan to assess eligibility for treatment with [177Lu]Lu-FF58. In the escalation part, different doses of [177Lu]Lu-FF58 will be tested to identify the recommended dose. The expansion part of the study will examine the safety and preliminary efficacy of [177Lu]Lu-FF58 at the recommended dose determined during the escalation part. The end of study will occur when at least 80% of the patients in the expansion part have completed the follow-up for disease progression or discontinued from the study for any reason, and all patients have completed treatment and the 36 month long term follow- up period, or the study is terminated early in which case all patients would also be followed up for safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1
Patients will receive 68Ga-FF58 and only patients with tumor uptake of 68Ga-FF58 will receive 177Lu-FF58.
干预措施: 68Ga-FF58 (Drug)
Arm 1
Patients will receive 68Ga-FF58 and only patients with tumor uptake of 68Ga-FF58 will receive 177Lu-FF58.
干预措施: 177Lu-FF58 (Drug)
结局指标
主要结局
Dose intensity for 177Lu-FF58
时间窗: From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks
Dose intensity for 177Lu-FF58 will be assessed and summarized using descriptive statistics. Dose intensity is computed as the ratio of actual cumulative dose received and actual duration of exposure.
Incidence and severity of dose limiting toxicities of 177Lu-FF58
时间窗: From start of study treatment until 6 weeks after
A dose limiting toxicity (DLT) is defined as any AE or abnormal laboratory value of CTCAE (v5.0) Grade 3 or higher that occurs within the DLT evaluation period (i.e., 6 weeks starting from the first administration of 177Lu-FF58) and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications.
Incidence and severity of adverse events and serious adverse events of 177Lu-FF58
时间窗: From start of study treatment until 180 days after the last dose of study treatment, assessed up to approximately 15 months
The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Dose modifications for 177Lu-FF58
时间窗: From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks
Dose modifications (dose interruptions and reductions) for 177Lu-FF58 will be assessed and summarized using descriptive statistics. The number of patients with dose modification and the reasons will be summarized by treatment groups.
次要结局
- Progression free survival (PFS)(From start of study treatment until date of progression, assessed up to approximately 34 months)
- Overall response rate (ORR)(From start of study treatment until date of progression, assessed up to approximately 34 months)
- Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA)(Cycle 1: Pre-infusion,beginning of infusion to first SPECT/CT image acquisition,first SPECT/CT image acquisition and 6 hours(hr) post-end-of infusion(EOI),6-24hr post-EOI,24-48hr post-EOI,48-72hr post-EOI. Cycle= 6 weeks or 3 weeks depending on schedule.)
- Time-activity curves (TACs) related to 177Lu-FF58 uptake in organs and tumor lesions(Cycle 1 Day 1, Cycle 1 Day 2 (24 hours (hr)), Cycle 1 Day 3 (48 hr), Cycle 1 Day 4 (72 hr), Cycle 1 Day 8 (168 hr). Cycle = 6 weeks or 3 weeks depending on schedule.)
- Imaging properties: Visual and quantitative assessment (expressed as SUV) and tumor-to-background ratio (TBR) of 68Ga-FF58 uptake in organs and tumor lesions over time(From Imaging until 1 hour (hr), 2 hr and 3 hr after 68Ga-FF58 administration)
- Disease control rate (DCR)(From start of study treatment until date of progression, assessed up to approximately 34 months)
- Duration of Response (DOR)(From start of study treatment until date of progression, assessed up to approximately 34 months)
- Volume of distribution during the terminal phase following intravenous elimination (Vz) from 177Lu-FF58 blood radioactivity data(Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.)
- Area Under the Curve (AUC) from 177Lu-FF58 blood radioactivity data(Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.)
- Total body clearance from 177Lu-FF58 blood radioactivity data(Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.)
- Observed maximum plasma concentration (Cmax) from 177Lu-FF58 blood radioactivity data(Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.)
- Terminal elimination half-life (T^1/2) from 177Lu-FF58 blood radioactivity data(Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 min, 1 hours(hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). Cycle=6 weeks or 3 weeks depending on schedule.)
- Absorbed dose of 177Lu-FF58(Cycle 1 Day 1, Cycle 1 Day 2 (24 hours (hr)), Cycle 1 Day 3 (48 hr), Cycle 1 Day 4 (72 hr), Cycle 1 Day 8 (168 hr). Cycle = 6 weeks or 3 weeks depending on schedule.)
- Incidence and severity of adverse events and serious adverse events of 68Ga-FF58(From Imaging visit until 14 days after 68Ga-FF58 administration, or until first dose of study treatment)