Advanced Solid TumorPhase 1NCT06147037
A Phase 1, Dose-escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours
A Phase 1 study testing FPI-2053, [111In]-FPI-2107 and [225Ac]-FPI-2068 in people with Advanced Solid Tumor and Metastatic Colorectal Carcinoma, run by AstraZeneca at 8 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Advanced Solid Tumor, Metastatic Colorectal Carcinoma, Head and Neck Squamous Cell Carcinoma
- What is being tested?
- FPI-2053, [111In]-FPI-2107 and [225Ac]-FPI-2068
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 31 Jul 2024to 31 Dec 2026
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States6 sites
Research Site
Chicago, Illinois, 60637
Research Site
Cleveland, Ohio, 44195
Research Site
Houston, Texas, 77030
Research Site
Omaha, Nebraska, 68130
Research Site
Palo Alto, California, 94304
Research Site
Seattle, Washington, 98109
Canada2 sites
Research Site
Montreal, Quebec, H2X 0A9
Research Site
Sherbrooke, Quebec, J1H 5N4
About this study
Official title: A Phase 1, First-in-human, Multicentre, Open-label, Dose Escalation Study of [225Ac]-FPI-2068 in Adult Patients With Advanced Solid Tumours
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).
Read the 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.
- Conditions
- Advanced Solid Tumor, Metastatic Colorectal Carcinoma, Head and Neck Squamous Cell Carcinoma, Non-small Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma, Gastric Cancer
- Being tested
- FPI-2053, [111In]-FPI-2107, [225Ac]-FPI-2068
- Keywords
- FPI-2068, FPI-2107, FPI-2053, Actinium-225, 225Ac, Indium-111, 111In, Solid tumors, Targeted alpha therapy, TAT, Epidermal growth factor receptor, EGFR, Mesenchymal-epithelial transition factor, cMET, Bispecific antibody, Radioimmuno-SPECT agent, Radioimmuno-therapeutic agent, Monoclonal antibody, Bifunctional chelating agent, Radiopharmaceutical therapy
- Medical subject headings
- Colorectal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Non-Small-Cell Lung, Stomach Neoplasms, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FPI-2053Drug
FPI-2053 is a bispecific antibody that targets EGFR and cMET
[111In]-FPI-2107Drug
[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).
[225Ac]-FPI-2068Drug
[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.
| Study group | Role | What they receive |
|---|---|---|
| Dose Exploration and Dose Escalation | Experimental | 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. Receives: Drug: FPI-2053; Drug: [111In]-FPI-2107; Drug: [225Ac]-FPI-2068 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate safety and tolerability of [111In]-FPI-2107, FPI-2053, and [225Ac]-FPI-2068
Frequency, duration, and severity of AEs, DLTs, and changes in clinical, laboratory, and ECG parameters compared to baseline
Measured: From informed consent up to approximately 5 years post last administration
Determine radiation dose of [111In]-FPI-2107 and [225Ac]-FPI-2068 to whole body, organs, and selected regions of interest.
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
Measured: Within 56 days of administration
Determine the RP2D of [225Ac]-FPI-2068, given with or without FPI-2053
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.
Measured: 56 days post administration
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.
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
Measured: 56 days post-administration
Secondary outcomes (4)
Assess preliminary anti-tumor activity of [225Ac]-FPI-2068
- Tumor assessments will be based on RECIST v1.1 (Eisenhauer et al, 2009) and will be performed every 8 weeks (± 1 weeks) after first [225Ac]-FPI-2068 dose. During Long term follow up will be every 3 months (± 2 weeks) for 2 years and then every 6 months for 3 years, or as clinically indicated or until disease progression.
- Percentage changes in total ctDNA (VAF), compared to baseline
Measured: Approximately 5 years post final administration
Tumor uptake of [111In]-FPI-2107
- Tumor uptake of [111In]-FPI-2107 in selected regions of interest on SPECT/CT and/or planar images
Measured: Within 56 days of administration
Pharmacokinetics (PK) of [111In]-FPI-2107, and [225Ac]-FPI-2068, by measuring changes in clearance, AUC, Cmax, and half-life.
- 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.
Measured: From first dose of investigation product until 56 days after the last dose of investigational product.
To assess the immunogenicity of [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053
- Presence of ADA for [111In]-FPI-2107, [225Ac]-FPI-2068, and FPI-2053
Measured: From first dose of investigation product until 56 days after the last dose of investigational product.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2023
- Study start31 Jul 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06147037
- Sponsor's protocol ID
- FPI-2068-101
- Status last verified
- Sep 2026
- First submitted
- 20 Nov 2023
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.