A Phase 1, First-in-human, Multicentre, Open-label, Dose Escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 13
- 试验地点
- 8
- 主要终点
- Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068
研究概览
简要总结
This is a first-in-human, Phase 1, non-randomized, multicenter, open-label clinical study designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics (PK) of [225Ac]-FPI-2068, [111In]-FPI-2107, and FPI-2053 in metastatic and/or recurrent solid tumors (HNSCC, NSCLC, mCRC, PDAC, GC, RCC).
详细描述
The study will be conducted in 2 parts:
Part A: optimization of the FPI-2053 dose (treatment with dose level 1 of [225Ac]-FPI-2068 - fixed dose).
Part B: dose escalation of [225Ac]-FPI-2068 with optimal FPI-2053. Part B will commence once the optimal dose of FPI-2053 is determined in Part A. The RP2D will be determined from Part B based on all available safety, efficacy, PK, and dosimetry information.
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 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically and/or cytologically confirmed solid tumor that is metastatic, locally advanced, recurrent or inoperable.
- •Disease that has progressed despite prior treatment, and for which additional effective standard therapy is not available or is contraindicated, not tolerable, or the participant refuses standard therapy.
- •Measurable disease as defined by RECIST Version 1.1
- •ECOG Performance status of 0 or 1
- •Adequate organ function
排除标准
- •Previous treatment with any systemic radiopharmaceutical
- •Prior anti-cancer therapy unless adequate washout and recovery from toxicities
- •Contraindications to or inability to perform the imaging procedures required in this study
- •Radiation therapy (RT) within 28 days prior to the first dose of [111In]-FPI-2107
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (≥ once per month)
- •Patients with known CNS metastatic disease unless treated and stable
研究组 & 干预措施
Dose Exploration and Dose Escalation
The study conducted in two parts: Part A Dose Exploration and Part B Dose Escalation
FPI-2053 dose exploration to determine the optimal pre-dose administration of FPI-2053 with a fixed dose of [225Ac]-FPI-2068.
[225Ac]-FPI-2068 dose escalation with the optimal dose of FPI-2053 as determined in Part A.
干预措施: FPI-2053 (Drug)
Dose Exploration and Dose Escalation
The study conducted in two parts: Part A Dose Exploration and Part B Dose Escalation
FPI-2053 dose exploration to determine the optimal pre-dose administration of FPI-2053 with a fixed dose of [225Ac]-FPI-2068.
[225Ac]-FPI-2068 dose escalation with the optimal dose of FPI-2053 as determined in Part A.
干预措施: [225Ac]-FPI-2068 (Drug)
Dose Exploration and Dose Escalation
The study conducted in two parts: Part A Dose Exploration and Part B Dose Escalation
FPI-2053 dose exploration to determine the optimal pre-dose administration of FPI-2053 with a fixed dose of [225Ac]-FPI-2068.
[225Ac]-FPI-2068 dose escalation with the optimal dose of FPI-2053 as determined in Part A.
干预措施: [111In]-FPI-2107 (Drug)
结局指标
主要结局
Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068
时间窗: From informed consent up to approximately 5 years post last administration
Frequency, duration, and severity of AEs, DLTs, and changes in clinical, laboratory, and ECG parameters compared to baseline
Determine radiation dose of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest.
时间窗: Within 56 days of administration
Changes in uptake of \[111In\]-FPI-2107 and projected RAD of \[225Ac\]-FPI-2068 by imaging following the administration of varying doses of FPI-2053
Determine the RP2D of [225Ac]-FPI-2068, given with or without FPI-2053
时间窗: 56 days post administration
Estimates of residence time and absorbed radiation doses to the whole body, organs, and selected regions of interest for \[111In\]-FPI-2107 and \[225Ac\]-FPI-2068.
Determine the effect of predose administration of varying doses of FPI-2053 on the radiation dosimetry of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest.
时间窗: 56 days post-administration
Changes in uptake of \[111In\]-FPI- 2107 and projected RAD of \[225Ac\]-FPI-2068 by imaging following the administration of varying doses of FPI-2053
次要结局
- To assess the immunogenicity of [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053(From first dose of investigation product until 56 days after the last dose of investigational product.)
- Pharmacokinetics (PK) of [111In]-FPI-2107, and [225Ac]-FPI-2068, by measuring changes in clearance, AUC, Cmax, and half-life.(From first dose of investigation product until 56 days after the last dose of investigational product.)
- Assess preliminary anti-tumor activity of [225Ac]-FPI-2068(Approximately 5 years post final administration)
- Tumor uptake of [111In]-FPI-2107(Within 56 days of administration)