A Phase 1/2 Study of [225Ac]-FPI-1966, [111In]-FPI-1967, and Vofatamab in Participants With FGFR3-expressing Advanced, Inoperable, Metastatic and/or Recurrent Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 6
- 主要终点
- Phase 1: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)
研究概览
简要总结
This first-in-human study evaluates safety, tolerability and distribution of [225Ac] FPI-1966, [111In]-FPI-1967, and vofatamab in patients with FGFR3-expressing solid tumors.
详细描述
In phase 1, cohort 1, the potential impact of pre-dose administration of vofatamab on the dosimetry, PK, safety, and tolerability of [225Ac]-FPI-1966 and [111In]-FPI-1967 will be evaluated.
In later phase 1 cohorts, [225Ac]-FPI-1966 will be evaluated at ascending dose levels. Participants will receive [111In]-FPI-1967 during the imaging screening period to assess FGFR3 expression and to determine biodistribution and estimate radiation exposure to critical organs.
Once the recommended phase 2 dose (RP2D) or regimen is established and confirmed, three tumour-agnostic expansion cohorts may be initiated in parallel.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed ICF prior to initiation of any study-specific procedures
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Histologically and/or cytologically documented diagnosis of locally advanced, inoperable, or metastatic solid tumours
- •Refractory to all standard treatments, or for whom standard treatment is not available, or tolerable, or is contraindicated, or the participant refuses standard therapy
- •Measurable disease per RECIST v. 1.1
- •Available tumour tissue (archival or fresh biopsy)
- •Adequate bone marrow, heart, liver, and kidney function
排除标准
- •Prior systemic radiopharmaceutical therapy within six months prior to the first dose of [111In]-FPI-1967
- •Prior radiation therapy (RT) to bone marrow > 20 Gy
- •RT within 30 days prior to the first dose of [111In]-FPI-1967
- •Prior anti-cancer treatment (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or investigational agents) within a certain amount of time prior to administration of the first dose of [111In]-FPI-1967
- •Concurrent serious co-morbidities that could limit participants' full participation and compliance
研究组 & 干预措施
Phase 1
Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered with or without pre-dosing with vofatamab.
干预措施: [111In]-FPI-1967 (Drug)
Phase 1
Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered with or without pre-dosing with vofatamab.
干预措施: [225Ac]-FPI-1966 (Drug)
Phase 1
Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered with or without pre-dosing with vofatamab.
干预措施: vofatamab (Biological)
Phase 2
Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered either with or without pre-administration of vofatamab, depending on the RP2D/regimen as determined in the phase 1 portion of the study.
干预措施: [225Ac]-FPI-1966 (Drug)
Phase 2
Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered either with or without pre-administration of vofatamab, depending on the RP2D/regimen as determined in the phase 1 portion of the study.
干预措施: [111In]-FPI-1967 (Drug)
Phase 2
Depending on assigned cohort, [In111]-FPI-1967/[225Ac]-FPI-1966 will be administered either with or without pre-administration of vofatamab, depending on the RP2D/regimen as determined in the phase 1 portion of the study.
干预措施: vofatamab (Biological)
结局指标
主要结局
Phase 1: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)
时间窗: Within one week of administration
Phase 1: Effect of pre-dose administration of vofatamab on the radiation dosimetry of [111In]-FPI-1967 and [225Ac]-FPI-1966.
时间窗: Within one week of administration
Phase 1: Maximum tolerated dose (MTD) of [225Ac]-FPI-1966
时间窗: Approximately 42 days post administration.
Phase 1: Phase 1: Incidence of AEs to evaluate safety and tolerability of [225Ac]-FPI-1966, [111In]-FPI-1967, and vofatamab.
时间窗: Approximately 2 years post final administration
Phase 2: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
时间窗: Up to two years post final administration.
次要结局
- Phase 1 and 2: Clearance for radioactivity and for the targeting antibody.(28 days post final [225Ac]-FPI-1966administration)
- Phase 1 and 2: Half-life for radioactivity and targeting antibody.(28 days post final [225Ac]-FPI-1966 administration)
- Phase 2: Radiation dose of [111In]-FPI-1967 and [225Ac]-FPI-1966 (whole body, organs, and selected regions of interest)(Within one week of administration)
- Phase 1 and 2: Tumour uptake of [111In]-FPI-1967 by evaluating SPECT/CT and/or planar images(Within one week of administration)
- Phase 1 and 2: Anti-tumour activity of [225Ac]-FPI-1966 regimen measured by response per RECIST v1.1(Approximately 2 years post final administration)
- Phase 1 and 2: Area under the curve (AUC) for radioactivity and targeting antibody(28 days post final [225Ac]-FPI-1966administration.)
- Phase 1 and 2: Maximum concentration after dosing (Cmax) for radioactivity and targeting antibody.(28 days post final[225Ac]-FPI-1966 administration)
- Phase 1: Changes in half-life for radioactivity and targeting antibody following pre-dose administration of vofatamab(28 days post final [225Ac]-FPI-1966 administration)
- Phase 1: Changes in clearance for radioactivity and targeting antibody following pre-dose administration of vofatamab(28 days post final [225Ac]-FPI-1966 administration)
- Phase 1: Changes in AUC for radioactivity and targeting antibody following pre-dose administration of vofatamab.(28 days post final [225Ac]-FPI-1966 administration)
- Phase 1: Changes in Cmax for radioactivity and targeting antibody following pre-dose administration of vofatamab.(28 days post final [225Ac]-FPI-1966 administration)