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A Phase 1 Study of [225Ac]-FPI-1434 Injection

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ClinicalTrials.gov Identifier: NCT03746431
Recruitment Status : Recruiting
First Posted : November 19, 2018
Last Update Posted : March 21, 2019
Sponsor:
Information provided by (Responsible Party):
Fusion Pharmaceuticals

Brief Summary:

The primary objectives are to:

  1. Evaluate the safety and tolerability of [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection in patients with advanced refractory solid tumours
  2. Determine the maximum tolerated dose of a single [225Ac]-FPI-1434 Injection

The secondary objectives are to:

  1. Obtain preliminary data on tumour uptake of [111In]-FPI-1547 Injection in cancer patients
  2. Determine the dosimetry of [111In]-FPI-1547 Injection (whole body and individual organs)
  3. Determine the pharmacokinetics of [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection
  4. Estimate the dosimetry for [225Ac]-FPI-1434 Injection (whole body and individual regions)
  5. Describe efficacy of [225Ac]-FPI-1434 Injection
  6. Assess the effect of [225Ac]-FPI-1434 Injection on the QTc interval
  7. Assess changes in human growth hormone (hGh), insulin-like growth factor (IGF)-1 and insulin-like growth binding protein 3 (IGFBP-3) following [111In]-FPI-1547 and [225Ac]-FPI-1434 injections

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: [111In]-FPI-1547 Injection Drug: [225Ac]-FPI-1434 Injection Phase 1

Detailed Description:
This is a first-in-human Phase 1, non-randomized, multi-center, open-label clinical trial designed to investigate the safety, tolerability, pharmacokinetics of [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection and to establish the maximum tolerated dose of a single [225Ac]-FPI-1434 Injection in patients with solid tumours with demonstrated tumour uptake of [111In]-FPI-1547.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of [225Ac]-FPI-1434 Injection in Patients With Advanced Solid Tumours
Actual Study Start Date : January 17, 2019
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : January 2021

Arm Intervention/treatment
Experimental: 1

Imaging:

All patients will receive [111In]-FPI-1547 185 MBq (5 mCi) for imaging.

Therapeutic:

Patients will receive a single injection of [225]-FPI-1434. Dose is per cohort assignment.

Drug: [111In]-FPI-1547 Injection
[111In]-FPI-1547is 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 (FPI-1397), and Indium-111.

Drug: [225Ac]-FPI-1434 Injection
[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 (FPI-1397), and actinium-225 (225Ac or Ac-225).




Primary Outcome Measures :
  1. Frequency and severity of adverse events [ Time Frame: 56 days. ]

Secondary Outcome Measures :
  1. Tumour uptake of [111In]-FPI-1547 Injection in selected regions of interest on SPECT/CT images. [ Time Frame: Within one week of the 111In]-FPI-1547 Injection. ]
  2. Radiation doses for selected organs and whole body both for [111In]-FPI-1547 and [225Ac]-FPI-1434. [ Time Frame: Three months. ]
  3. Radiation doses for tumour lesions for [225Ac]-FPI-1434. [ Time Frame: Three months. ]
  4. Clearance for radioactivity and for the targeting antibody. [ Time Frame: Three months. ]
  5. Area under the curve (AUC) for radioactivity and for the targeting antibody. [ Time Frame: Three months. ]
  6. Cmax for radioactivity and for the targeting antibody. [ Time Frame: Three months. ]
  7. Half-life for radioactivity and for the targeting antibody. [ Time Frame: Three months. ]
  8. Objective response rate (sum of complete and partial response) per RECIST 1.1 or PCWG3 guidelines, duration of response and progression free survival. [ Time Frame: Approximately one year. ]
  9. Changes in the QTc interval in milliseconds after [225Ac]-FPI-1434 treatment, compared to baseline. [ Time Frame: Approximately 24 hours from the time of [225Ac]-FPI-1434 Injection administration. ]
  10. Changes in human growth hormone (hGh), insulin-like growth factor (IGF)-1 and insulin-like growth binding protein 3 (IGFBP-3) following [111In]-FPI-1547 and [225Ac]-FPI-1434 injections. [ Time Frame: 56 days. ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥18 years old.
  2. 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.
  3. At least 1 measurable lesion (≥ 20 mm in largest diameter [≥ 20 mm in shortest diameter if lymph node]).
  4. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
  5. Life expectancy of greater than 3 months as judged by the treating physician.
  6. Available tumour tissue (either archival or fresh biopsy) for IGF-1R immunohistochemistry. Submission of the tissue is not required prior to enrolment.
  7. Adequate bone marrow reserves without the use of hematopoietic growth factors, red cell or platelet transfusion as evidenced by:

    1. Absolute neutrophil count ≥ 1,500/ mm^3 (≥ 1.5 x 10^9/L)
    2. Platelet count ≥ 100,000/ mm^3 (≥ 100 x 10^9/L)
    3. Hemoglobin ≥ 9 g/dL (≥ 90 g/L)
  8. Adequate renal function as evidenced by a creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault Equation. Actual body weight should be used for calculating creatinine clearance using the Cockcroft-Gault Equation.
  9. Adequate hepatic function as evidenced by:

    1. Serum total bilirubin ≤ 1.5x upper limit of normal (ULN), unless patient has Gilbert's disease
    2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN in patients with known liver metastasis)
  10. Other laboratory results, vital signs and ECG are judged by the Investigator to be acceptable for enrolment into the study.
  11. Females of childbearing potential must have a negative pregnancy test results during the general and imaging screening periods.
  12. Females of childbearing potential and all men must agree to use at least two highly effective forms of contraception one of which must be a barrier method, or agree to remain abstinent, for the duration of study participation and 3 months after completion of the study.
  13. Ability to understand and the willingness to sign a written informed consent document.
  14. In the judgement of the Investigator, the patient is expected to be compliant and have a high probability of completing the study.

Exclusion Criteria:

  1. Received a systemic therapeutic radiopharmaceutical within 6 months prior to enrolment into this study.
  2. Contraindications to or inability to perform the required imaging procedures in this study (e.g. inability to lay flat for the image acquisitions, etc.)
  3. Uncontrolled brain metastasis, including but not limited to need for treatment with steroids, surgery or radiation therapy.
  4. Anticancer therapy (including investigations agents) or external beam radiation therapy within 14 days of the dosing of [111In]-FPI-1547 (6 weeks for mitomycin-C). Ongoing androgen deprivation therapy for prostate cancer, thyroid stimulating hormone suppression for differentiated thyroid cancer, somatostatin analogues for neuroendocrine tumours are NOT considered exclusion criteria.
  5. Prior organ transplantation, including stem cell transplantation.
  6. Any prior treatment with nitrosoureas and actinomycin-D.
  7. Clinical relevant proteinuria (e.g. urinary dipstick analysis for proteins is 3+ [300 mg/dL or 4+ [1,000 mg/dL], or daily urinary excretion > 500 mg/dL).
  8. Known or suspect allergies or contraindications to the Investigational Products or any component of the investigational drug formulation.
  9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, diabetes (random blood sugar during screening ≥250 mg/dL [≥ 13.9 mmol/L]), or psychiatric illness/social situations that would limit compliance with study requirements.
  10. Received > 20 Gy prior radiation to large areas of the bone marrow (e.g. external radiation therapy to whole pelvis)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03746431


Contacts
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Contact: Istvan Molnar, MD 1-888-506-4215 molnar@fusionpharma.com

Locations
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Canada, Ontario
Juravinski Cancer Center - Hamilton Health Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Princess Margaret Cancer Centre Not yet recruiting
Toronto, Ontario, Canada, M5G 2C1
Canada, Quebec
Centre Hospitalier De I'Universite de Montreal Recruiting
Montréal, Quebec, Canada, H2X 0C1
Quebec University Hospital- Laval Not yet recruiting
Québec City, Quebec, Canada, G1R 2J6
Sponsors and Collaborators
Fusion Pharmaceuticals

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Responsible Party: Fusion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03746431     History of Changes
Other Study ID Numbers: FPX-01-01
First Posted: November 19, 2018    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Mecasermin
Growth Substances
Physiological Effects of Drugs