A Phase I/IIa Image-Guided, Alpha-Particle Therapy Study of [203Pb]Pb-PSV359 and [212Pb]Pb-PSV359 in Patients With Solid Tumors That Are Known to be Fibroblast Activation Protein (FAP)-Positive
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 112
- 试验地点
- 12
- 主要终点
- Determination of safety and tolerability of [212Pb]Pb-PSV359
研究概览
简要总结
Phase I/IIa image-guided, alpha-particle therapy study of [203Pb]Pb-PSV359 and [212Pb]Pb-PSV359 in patients with solid tumors that are known to be Fibroblast Activation Protein (FAP)-positive.
详细描述
This is a prospective, multi-center open label dose finding, dose expansion study of [212Pb]Pb-PSV359 in subjects with a positive Fibroblast Activation Protein (FAP) imaging scan with imaging agent.
FAP is specifically expressed on the surface of cancer-associated fibroblasts in some tumor tissues and therefore is an attractive target in the diagnosis and treatment of various cancers. Lead-212 ([212Pb]Pb-) based peptide-radiopharmaceuticals are an emerging class of targeted alpha-particle cancer therapies that have potential to improve delivery of a highly effective form of radiation.
This study will be conducted in 2 parts:
Part 1: Dose-escalation: [212Pb]Pb-PSV359 is administered in escalating doses to determine the Maximum Tolerated radioactivity (MTD) Dose and potential recommended Phase 2 dose (RP2D).
Part 2: Dose-expansion: This part will enroll subjects in expansion cohorts based on the identified MTD and RP2D for the selection of [212Pb]Pb-PSV359 doses for further clinical development.
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 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years
- •Satisfactory organ function as determined by laboratory testing
- •Eastern Cooperative Oncology Group performance (ECOG) status of 0 to 1
- •Life expectancy > 3 months
- •Progressive disease despite standard therapy or for whom no standard therapy exists
- •Positive [203Pb]Pb-PSV359 SPECT/CT scan showing uptake of [203Pb]Pb-PSV359 in at least 1 known lesion on the 1-hour SPECT/ CT scan
- •Histological, pathological, and/or cytological confirmation of solid tumor malignancy that is locally advanced or metastatic
排除标准
- •Known hypersensitivity to the active agent or any of the excipients
- •Active secondary malignancy
- •Pregnancy or breastfeeding a child
- •Known brain metastases
- •Known active or uncontrolled infections requiring ongoing antifungals or antibiotics in the 3 days prior to enrollment
- •Known medical condition which would make this protocol unreasonably hazardous for the patient
- •Existence of any medical or social issues likely to interfere with study conductor that may cause increased risk to the subject or to others, e.g., lack of ability to follow radiation safety precautions
- •Medical history of a condition resulting in a severe allergic reaction such as anaphylaxis or angioedema to known components of the investigational product or excipients
- •Major surgery within 21 days prior to the administration of [212Pb]Pb-PSV359; the subject must be sufficiently recovered and stable before treatment administration
- •Diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to enrollment into the study
- •Current abuse of alcohol or illicit drugs
- •Treatment with any live/attenuated vaccine in the 7 days prior to enrollment
- •Previous treatment with any systemic anticancer therapy within 4 weeks prior to treatment on study
研究组 & 干预措施
Dose Escalation
- Enrolled subjects are administered [203Pb]Pb-PSV359 (7mCi) for imaging FAP-expressing cancers.
- Approximately Four cohorts of [212Pb]Pb-PSV359 dose levels will be explored for determining Recommended Phase 2 Dose (RP2D). Study subjects will be assigned to cohorts sequentially.
干预措施: [212Pb]Pb-PSV359 (Drug)
Dose Escalation
- Enrolled subjects are administered [203Pb]Pb-PSV359 (7mCi) for imaging FAP-expressing cancers.
- Approximately Four cohorts of [212Pb]Pb-PSV359 dose levels will be explored for determining Recommended Phase 2 Dose (RP2D). Study subjects will be assigned to cohorts sequentially.
干预措施: [203Pb]Pb-PSV359 (Drug)
Dose Expansion
- Enrolled subjects are administered [203Pb]Pb-PSV359 (7mCi) for imaging FAP-expressing cancers.
- Enrolled subjects are administered [212Pb]Pb-PSV359 (RP2D determined previously) for treatment of FAP-expressing cancers
干预措施: [203Pb]Pb-PSV359 (Drug)
Dose Expansion
- Enrolled subjects are administered [203Pb]Pb-PSV359 (7mCi) for imaging FAP-expressing cancers.
- Enrolled subjects are administered [212Pb]Pb-PSV359 (RP2D determined previously) for treatment of FAP-expressing cancers
干预措施: [212Pb]Pb-PSV359 (Drug)
结局指标
主要结局
Determination of safety and tolerability of [212Pb]Pb-PSV359
时间窗: Up to 3 years
Incidence and severity of treatment-related adverse events following a single and each repeated administration of \[212Pb\]Pb-PSV359 is determined
Determination of safety and tolerability of [203Pb]Pb-PSV359
时间窗: 30 days (±1day) post dose
Incidence and severity of treatment-related adverse events following a single administration of \[203Pb\]Pb-PSV359 is determined
Determination of safety and tolerability of [212Pb]Pb-PSV359
时间窗: Up to 3 years
Incidence and severity of treatment-related adverse events following a single and each repeated administration of \[212Pb\]Pb-PSV359 is determined
To determine the recommended phase 2 dose of [212Pb]Pb-PSV359
时间窗: Up to approximately 6 months
The recommended phase 2 dose as determined by cohort observations and review by the Safety Monitoring Committee
次要结局
- Determination of duration of response following treatment with [212Pb]Pb-PSV359(Up to 3 years)
- Determination of progression free survival following treatment with [212Pb]Pb-PSV359(Up to 3 years)
- Determination of duration of response following treatment with [212Pb]Pb-PSV359(Up to 3 years)
- Determination of progression free survival following treatment with [212Pb]Pb-PSV359(Up to 3 years)
- Estimation of biodistribution of 203Pb PSV 359 using SPECT/CT scans(Up to approximately 3 years)
- Determination of pharmacokinetic properties of [203Pb]Pb-PSV359 and [212Pb]Pb-PSV359(up to approximately 3 years)
- Determination of pharmacokinetic properties of [203Pb]Pb-PSV359 and [212Pb]Pb-PSV359(Up to approximately 3 yrs)