This is a first-in-human, Phase 1/2, non-randomized, multi-centre, open-label clinical study designed to investigate safety, tolerability, dosimetry, biodistribution, and PK of [225Ac] FPI-1966, [111In]-FPI-1967, and vofatamab and the preliminary anti-tumour activity of [225Ac]-FPI-1966 in participants with FGFR3-expressing advanced, inoperable, metastatic, and/or recurrent solid tumours. Phase 1 consists of five multiple dose escalation cohorts. Phase 2 consists of two tumour-specific cohorts and one basket cohort.
Advanced, Inoperable, Metastatic and/or Recurrent Solid Tumours
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 Phase 1, Cohort 1 of the study. [225Ac]-FPI-1966 will be evaluated in Phase 1 across 5 planned, ascending dose cohorts using a 3 + 3 dose escalation design. Participants will receive 185 MBq of [111In]-FPI-1967 during the imaging screening period to determine biodistribution and estimate radiation exposure to critical organs.
Once the recommended phase 2 dose (RP2D) regimen is established and confirmed, three expansion cohorts may be initiated in parallel.
- Signed ICF prior to initiation of any study-specific procedures
- Male and female participants, ≥ 18 years of age, with 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 with at least one non-nodal lesion of ≥ 20 mm in the longest diameter
- Available tumour tissue (either archival within the last two years or fresh biopsy) for FGFR3 immunohistochemistry and biomarker analysis (submission of tissue not required prior to enrolment)
- Adequate bone marrow, cardiovascular, hepatic, and renal function
- 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 five half-lives or four weeks, whichever is shorter, prior to administration of the first dose of [111In]-FPI-1967
- Concurrent serious co-morbidities that could limit participants' full participation and compliance
Please contact a member of the study team for the full inclusion and exclusion criteria.