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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03746431




Registration number
NCT03746431
Ethics application status
Date submitted
9/11/2018
Date registered
19/11/2018
Date last updated
22/12/2023

Titles & IDs
Public title
A Phase 1/2 Study of [225Ac]-FPI-1434 Injection
Scientific title
A Phase 1/2 Study of [225Ac]-FPI-1434 Injection in Patients With Locally Advanced or Metastatic Solid Tumours
Secondary ID [1] 0 0
FPX-01-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumours 0 0
Endometrial Cancer 0 0
Cervical Cancer 0 0
Ovarian Cancer 0 0
Breast Cancer 0 0
Triple Negative Breast Cancer (TNBC) 0 0
HER2-negative Breast Cancer 0 0
Head and Neck Squamous Cell Carcinoma (HNSCC) 0 0
Adrenocortical Carcinoma 0 0
Uveal Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Head and neck
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - [111In]-FPI-1547 Injection
Treatment: Drugs - [225Ac]-FPI-1434 Injection multi-dose
Other interventions - FPI-1175 Infusion
Treatment: Drugs - [225Ac]-FPI-1434 Injection single-dose

Experimental: [225Ac]-FPI-1434 Single-Dose Escalation -

Experimental: [225Ac]-FPI-1434 Multi-Dose Escalation - [225Ac]-FPI-1434 treatment with or without pre-administration of FPI-1175 (cold antibody).

Experimental: FPI-1175 Cold Antibody -

Experimental: [225Ac]-FPI-1434 Multi-Dose - Phase 2 Tumour Cohort - Head & Neck Squamous Cell Carcinoma (HNSCC), Endometrial Cancer, Cervical Cancer, Ovarian Cancer, Triple Negative Breast Cancer (TNBC), HER2-negative, Adrenocortical Carcinoma (ACC), Uveal Melanoma, [225Ac]-FPI-1434 treatment with or without pre-administration of FPI-1175 (cold antibody).


Treatment: Drugs: [111In]-FPI-1547 Injection
[111In]-FPI-1547 is a targeted radioimmuno-imaging agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Indium-111, a radionuclide. Patients will receive [111In]-FPI-1547 Injection of 185 MBq (5 mCi) for imaging.

Treatment: Drugs: [225Ac]-FPI-1434 Injection multi-dose
[225Ac]-FPI-1434 is a targeted alpha radioimmuno-therapeutic agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Actinium-225, an alpha-emitting radionuclide. Patients will receive multiple doses of [225Ac]-FPI-1434 Injection. Dose is per cohort assignment.

Other interventions: FPI-1175 Infusion
FPI-1175 is an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody without a radioisotope. Patients will receive FPI-1175 Infusion at a dose per cohort assignment.

Treatment: Drugs: [225Ac]-FPI-1434 Injection single-dose
[225Ac]-FPI-1434 is a targeted alpha radioimmuno-therapeutic agent that consists of FPI-1175, an insulin-like growth factor-1 receptor (IGF-1R)-targeting humanized monoclonal antibody, a bifunctional chelate, and Actinium-225, an alpha-emitting radionuclide. Patients will receive a single dose of [225]-FPI-1434 Injection. Dose is per cohort assignment.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose Escalation: Incidence of adverse events (AEs).
Timepoint [1] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.
Primary outcome [2] 0 0
Single-Dose Escalation: Incidence of dose limiting toxicities (DLTs).
Timepoint [2] 0 0
8 weeks.
Primary outcome [3] 0 0
Multi-Dose Escalation: Incidence of DLTs.
Timepoint [3] 0 0
6 weeks.
Primary outcome [4] 0 0
Dose Escalation: Incidence of clinically significant clinical laboratory abnormalities.
Timepoint [4] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.
Primary outcome [5] 0 0
Dose Escalation: Changes in electrocardiogram (ECG) parameters (PR, QRS, QT, and QTc intervals).
Timepoint [5] 0 0
4 weeks post final [225Ac]-FPI-1434 Injection.
Primary outcome [6] 0 0
Cold Antibody Sub-Study: Changes in uptake of [111In]-FPI-1547 Injection following FPI-1175 Infusion in selected regions of interest on SPECT/CT images.
Timepoint [6] 0 0
Within two weeks of the first [111In]-FPI-1547 Injection.
Primary outcome [7] 0 0
Cold Antibody Sub-Study: Changes in radiation dose estimates for selected tissues, organs and whole body both for [111In]-FPI-1547 and [225Ac]-FPI-1434 Injection at various dose levels following FPI-1175 Infusion.
Timepoint [7] 0 0
Within two weeks of the first [111In]-FPI-1547 Injection.
Primary outcome [8] 0 0
Evaluate anti-tumour activity of [225Ac]-FPI-1434 regimen
Timepoint [8] 0 0
Approximately one year post final [225Ac]-FPI-1434 injection.
Primary outcome [9] 0 0
Objective response rate (ORR) RECIST v1.1.
Timepoint [9] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.
Secondary outcome [1] 0 0
Dose Escalation and Cold Antibody Sub-Study: Tumour uptake of [111In]-FPI-1547 in selected regions of interest on SPECT/CT images.
Timepoint [1] 0 0
Dose Escalation: Within one week of the [111In]-FPI-1547 Injection. Cold-Antibody Sub-Study: Within two weeks of the first [111In]-FPI-1547 Injection.
Secondary outcome [2] 0 0
Dose Escalation: Radiation doses for selected organs and whole body both for [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.
Timepoint [2] 0 0
Within one week of the [111In]-FPI-1547 Injection.
Secondary outcome [3] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Changes in radiation absorbed doses for tumour lesions for [225Ac]-FPI-1434.
Timepoint [3] 0 0
Dose Escalation: Within one week of the [111In]-FPI-1547 Injection. Cold-Antibody Sub-Study: Within two weeks of the first [111In]-FPI-1547 Injection.
Secondary outcome [4] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Clearance for radioactivity and for the targeting antibody.
Timepoint [4] 0 0
4 weeks post final [225Ac]-FPI-1434 Injection.
Secondary outcome [5] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Area under the curve (AUC) for radioactivity and for the targeting antibody.
Timepoint [5] 0 0
4 weeks post final [225Ac]-FPI-1434 Injection.
Secondary outcome [6] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Cmax for radioactivity and for the targeting antibody.
Timepoint [6] 0 0
4 weeks post final [225Ac]-FPI-1434 Injection.
Secondary outcome [7] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Half-life for radioactivity and for the targeting antibody.
Timepoint [7] 0 0
4 weeks post final [225Ac]-FPI-1434 Injection.
Secondary outcome [8] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Objective response rate (ORR) (sum of complete and partial response) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Prostate Cancer Working Group 3 (PCWG3) guidelines.
Timepoint [8] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.
Secondary outcome [9] 0 0
Dose Escalation: Changes in the corrected QT (QTc) interval in milliseconds after [225Ac]-FPI-1434 treatment, compared to baseline.
Timepoint [9] 0 0
Approximately 24 hours from the time of [225Ac]-FPI-1434 Injection administration.
Secondary outcome [10] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Changes in human growth hormone (hGh) following [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.
Timepoint [10] 0 0
4 weeks post final [225Ac]-FPI-1434 Injection.
Secondary outcome [11] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Changes in insulin-like growth factor 1 (IGF-1) following [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.
Timepoint [11] 0 0
4 weeks post final [225Ac]-FPI-1434 Injection.
Secondary outcome [12] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Changes in insulin-like growth factor binding protein 3 (IGFBP-3) following [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection.
Timepoint [12] 0 0
4 weeks post final [225Ac]-FPI-1434 Injection.
Secondary outcome [13] 0 0
Cold Antibody Sub-Study: Incidence of AEs.
Timepoint [13] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.
Secondary outcome [14] 0 0
Cold Antibody Sub-Study: Incidence of clinically significant clinical laboratory abnormalities.
Timepoint [14] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.
Secondary outcome [15] 0 0
Cold Antibody Sub-Study: Changes in ECG parameters (PR, QRS, QT, and QTc intervals).
Timepoint [15] 0 0
4 weeks post final [225Ac]-FPI-1434 Injection.
Secondary outcome [16] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Time to response (TTR).
Timepoint [16] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.
Secondary outcome [17] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Duration of response (DoR).
Timepoint [17] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.
Secondary outcome [18] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Progression free survival (PFS).
Timepoint [18] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.
Secondary outcome [19] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Time to Progression (TTP).
Timepoint [19] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.
Secondary outcome [20] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Disease control rate (DCR).
Timepoint [20] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.
Secondary outcome [21] 0 0
Dose Escalation and Cold-Antibody Sub-Study: Overall survival (OS).
Timepoint [21] 0 0
Approximately one year post final [225Ac]-FPI-1434 Injection.

Eligibility
Key inclusion criteria
1. Pathologically documented, definitively diagnosed, advanced solid tumour that is
refractory to all standard treatment, for which no standard treatment is available, or
it is contraindicated, or the patient refuses standard therapy.

2. Measurable or evaluable disease in accordance with RECIST 1.1.

3. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.

4. Life expectancy of greater than 3 months as judged by the treating physician.

5. Available tumour tissue (either archival or fresh biopsy) for IGF-1R
immunohistochemistry. Submission of the tissue is not required prior to enrollment.

6. Adequate heart, kidney, and liver function

7. Adequate bone marrow reserves

8. Ability to understand and the willingness to sign a written informed consent document.

Phase 2 Specific

9. Histologically and/or cytologically documented diagnosis of locally advanced,
inoperable, metastatic, or recurrent solid tumour types: endometrial, cervical,
ovarian, TNBC, HER 2-negative breast, HNSCC, ACC, or uveal melanoma.

10. Have measurable disease per RECIST 1.1 Failure to respond to standard systemic
therapy, or for whom standard or curative systemic therapy does not exist or is not
tolerable.

Imaging Eligibility

11. Prior to the initial [225Ac]-FPI-1434 cycle: Sufficient target expression in at least
1 lesion following [111In]-FPI-1547 and SPECT imaging.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Systemic therapeutic radiopharmaceutical within 6 months prior to enrollment into this
study.

2. Contraindications to or inability to perform the required imaging procedures in this
study (e.g., inability to lay flat during scan time)

3. Uncontrolled brain metastasis, including but not limited to the need for treatment
with steroids, surgery or radiation therapy.

4. Anticancer therapy (including investigational agents) or external beam radiation
therapy within 14 days of the dosing of [111In]-FPI-1547

5. Has known additional malignancy that is progressing or has required active treatment
within the past 3 years. Patients with basal cell carcinoma of the skin, squamous cell
carcinoma of the skin or carcinoma in situ (e.g., breast cancer, cervical cancer,
prostate) that have undergone potentially curative therapy are not excluded.

6. Residual CTCAE = Grade 2 side effects of prior therapy, with the exception of residual
grade 2 alopecia.

7. Prior organ transplantation, including stem cell transplantation.

8. Any prior treatment with nitrosoureas or actinomycin-D.

9. Clinically relevant levels of protein in the urine

10. Known or suspected allergies or contraindications to the Investigational Products or
any component of the investigational drug formulation.

11. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, diabetes, or psychiatric illness/social situations that would limit
compliance with study requirements.

12. Received > 20 Gy prior radiation to large areas of the bone marrow

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/01/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2026
Actual
Sample size
Target
253
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Fusion Pharmaceuticals Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a first-in-human Phase 1/2, non-randomized, multi-centre, open-label clinical study
designed to investigate safety, tolerability, PK, and preliminary anti-tumour activity of
[225Ac]-FPI-1434 (radioimmuno-therapeutic agent) in patients with solid tumours that
demonstrate uptake of [111In]-FPI-1547 (radioimmuno-imaging agent), and to establish the
maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of repeat doses of
[225Ac]-FPI-1434 Injection in patients with solid tumours that demonstrate uptake of
[111In]-FPI-1547 (radioimmuno-imaging agent).
Trial website
https://clinicaltrials.gov/ct2/show/NCT03746431
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Julia Kazakin, MD
Address 0 0
Fusion Pharmaceuticals Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
[email protected]
Address 0 0
Country 0 0
Phone 0 0
+1 (888) 506-4215
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03746431