A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: FPI-2053
FPI-2053 is a bispecific antibody that targets EGFR and cMET
Drug: [111In]-FPI-2107
[111In]-FPI-2107 is an imaging agent in which indium-111 is conjugated to FPI-2053.
Participants will have a fixed dose of [111In]-FPI-2107 followed by imaging scans (with or without pre-administration of FPI-2053).
Drug: [225Ac]-FPI-2068
[225Ac]-FPI-2068 is a radiopharmaceutical therapy in which an alpha emitter, actinium-225, is conjugated to FPI-2053.
Participants will be dosed through IV administration every 56 days for up to 3 cycles of the Treatment Period.
|
Outcome Measures
Primary Outcome Measures
- Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068 [Approximately 4 years post final administration]
• Incidence of Adverse Events and evaluation of dosimetry
- Radiation dose of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest. [Within 56 days of administration]
For Part A, evaluate the impact of pre-dose administration of FPI-2053 on the radiation dosimetry of [111In]-FPI-2107 (whole body, organs, and selected regions of interest) Estimate the effect of pre-dose administration of FPI-2053 on the radiation dosimetry of [225Ac]-FPI-2068 (whole body, organs, and selected regions of interest)
- Maximum tolerated dose of [225Ac]-FPI-2068 and FPI-2053 [56 days post administration]
Determine the RP2D of [225Ac]-FPI-2068, given with or without FPI-2053
Secondary Outcome Measures
- Assess preliminary anti-tumor activity of [225Ac]-FPI-2068 [Approximately 4 years post final administration]
• Tumour assessments will be based on RECIST v1.1 (Eisenhauer et al, 2009) and will be performed approximately every 8 weeks (± 1 week) after the first [225Ac]-FPI-2068 dose, or as clinically indicated.
- Tumor uptake of [111In]-FPI-2107 [Approximately 56 days of final administration]
• Tumor uptake of [111In]-FPI-2107 in selected regions of interest on SPECT/CT and/or planar images
- Pharmacokinetics (PK) of [111In]-FPI-2107, and [225Ac]-FPI-2068, by measuring changes in clearance, AUC, Cmax, and half-life. [Approximately 56 days of final administration]
• Determine the plasma concentrations and PK parameters of [111In]-FPI-2107, and [225Ac]-FPI-2068 and the effect of pre-dose administration of FPI-2053 on the plasma concentrations and PK parameters of [111In]-FPI-2107.
- To assess the immunogenicity of [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053 [Approximately 56 days of final administration]
• Presence of ADA for [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053
Eligibility Criteria
Criteria
Key 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
Key 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hoag Hospital | Irvine | California | United States | 92618 |
| 2 | University of Chicago | Chicago | Illinois | United States | 60637 |
| 3 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
Sponsors and Collaborators
- Fusion Pharmaceuticals Inc.
- AstraZeneca
Investigators
- Study Director: Lisa Jean-Louis, Fusion Pharmaceuticals Inc.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- FPI-2068-101