A Phase 1, First-in-human, Multicentre, Open-label, Dose Escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours
Overview
- Phase
- Phase 1
- Intervention
- [111In]-FPI-2107
- Conditions
- Metastatic Colorectal Carcinoma
- Sponsor
- AstraZeneca
- Enrollment
- 70
- Locations
- 15
- Primary Endpoint
- Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068
- Status
- Recruiting
- Last Updated
- 4 days ago
Overview
Brief Summary
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).
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
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.
Intervention: [111In]-FPI-2107
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.
Intervention: FPI-2053
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.
Intervention: [225Ac]-FPI-2068
Outcomes
Primary Outcomes
Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068
Time Frame: 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.
Time Frame: 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
Time Frame: 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.
Time Frame: 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
Secondary Outcomes
- 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)