A Phase 1/2 Study of [225Ac]-FPI-1434 Injection

• ClinicalTrials.gov Identifier: NCT03746431
• Recruitment Status: Recruiting
• First Posted: November 19, 2018
• Last Update Posted: March 3, 2022
• Sponsor: Fusion Pharmaceuticals Inc.
• Information provided by (Responsible Party): Fusion Pharmaceuticals Inc.

Study Description

Brief Summary:

This is a first-in-human Phase 1/2, non-randomized, multi-centre, open-label clinical trial designed to investigate safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumour activity of [111In]-FPI-1547 Injection (radioimmuno-imaging agent) and [225Ac]-FPI-1434 Injection (radioimmuno-therapeutic) 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. The study consists of a Phase 1 portion that includes dose ascending cohorts (single and multi-dosing administration with/without cold antibody), a Cold Antibody Sub-Study, and a Phase 2 portion that includes tumour-specific cohorts.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumours; Actinium-225; Antineoplastic Agents; Targeted Alpha Therapy; Radioimmunoconjugate	Drug: [111In]-FPI-1547 Injection; Drug: [225Ac]-FPI-1434 Injection multi-dose; Biological: FPI-1175 Infusion; Drug: [225Ac]-FPI-1434 Injection single-dose	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 227 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study of [225Ac]-FPI-1434 Injection in Patients With Locally Advanced or Metastatic Solid Tumours
• Actual Study Start Date: January 17, 2019
• Estimated Primary Completion Date: June 2022
• Estimated Study Completion Date: June 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Dose Escalation: Incidence of adverse events (AEs). [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
   Phase 1
2. Single-Dose Escalation: Incidence of dose limiting toxicities (DLTs). [ Time Frame: 8 weeks. ]
   Phase 1
3. Multi-Dose Escalation: Incidence of DLTs. [ Time Frame: 6 weeks. ]
   Phase 1
4. Dose Escalation: Incidence of clinically significant clinical laboratory abnormalities. [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
   Phase 1
5. Dose Escalation: Changes in electrocardiogram (ECG) parameters (PR, QRS, QT, and QTc intervals). [ Time Frame: 4 weeks post final [225Ac]-FPI-1434 Injection. ]
   Phase 1
6. 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. [ Time Frame: Within two weeks of the first [111In]-FPI-1547 Injection. ]
   Phase 1
7. 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. [ Time Frame: Within two weeks of the first [111In]-FPI-1547 Injection. ]
   Phase 1
8. Evaluate anti-tumour activity of [225Ac]-FPI-1434 regimen [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 injection. ]
   Phase 2

Secondary Outcome Measures :

1. Dose Escalation and Cold Antibody Sub-Study: Tumour uptake of [111In]-FPI-1547 in selected regions of interest on SPECT/CT images. [ Time Frame: 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. ]
   Phase 1 and 2
2. Dose Escalation: Radiation doses for selected organs and whole body both for [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection. [ Time Frame: Within one week of the [111In]-FPI-1547 Injection. ]
   Phase 1 and 2
3. Dose Escalation and Cold-Antibody Sub-Study: Changes in radiation absorbed doses for tumour lesions for [225Ac]-FPI-1434. [ Time Frame: 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. ]
   Phase 1 and 2
4. Dose Escalation and Cold-Antibody Sub-Study: Clearance for radioactivity and for the targeting antibody. [ Time Frame: 4 weeks post final [225Ac]-FPI-1434 Injection. ]
   Phase 1 and 2
5. Dose Escalation and Cold-Antibody Sub-Study: Area under the curve (AUC) for radioactivity and for the targeting antibody. [ Time Frame: 4 weeks post final [225Ac]-FPI-1434 Injection. ]
   Phase 1 and 2
6. Dose Escalation and Cold-Antibody Sub-Study: Cmax for radioactivity and for the targeting antibody. [ Time Frame: 4 weeks post final [225Ac]-FPI-1434 Injection. ]
   Phase 1 and 2
7. Dose Escalation and Cold-Antibody Sub-Study: Half-life for radioactivity and for the targeting antibody. [ Time Frame: 4 weeks post final [225Ac]-FPI-1434 Injection. ]
   Phase 1 and 2
8. 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. [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
   Phase 1 and 2
9. Dose Escalation: Changes in the corrected QT (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. ]
   Phase 1 and 2
10. Dose Escalation and Cold-Antibody Sub-Study: Changes in human growth hormone (hGh) following [111In]-FPI-1547 Injection and [225Ac]-FPI-1434 Injection. [ Time Frame: 4 weeks post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2
11. 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. [ Time Frame: 4 weeks post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2
12. 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. [ Time Frame: 4 weeks post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2
13. Cold Antibody Sub-Study: Incidence of AEs. [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2
14. Cold Antibody Sub-Study: Incidence of clinically significant clinical laboratory abnormalities. [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2
15. Cold Antibody Sub-Study: Changes in ECG parameters (PR, QRS, QT, and QTc intervals). [ Time Frame: 4 weeks post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2
16. Dose Escalation and Cold-Antibody Sub-Study: Time to response (TTR). [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2
17. Dose Escalation and Cold-Antibody Sub-Study: Duration of response (DoR). [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2
18. Dose Escalation and Cold-Antibody Sub-Study: Progression free survival (PFS). [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2
19. Dose Escalation and Cold-Antibody Sub-Study: Time to Progression (TTP). [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2
20. Dose Escalation and Cold-Antibody Sub-Study: Disease control rate (DCR). [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2
21. Dose Escalation and Cold-Antibody Sub-Study: Overall survival (OS). [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
    Phase 1 and 2

Other Outcome Measures:

1. Dose Escalation: Correlation of uptake of [111In]-FPI-1547 with observed toxicities following therapeutic administration of [225Ac]-FPI-1434 Injection. [ Time Frame: Approximately one year post final [225Ac]-FPI-1434 Injection. ]
2. Dose Escalation: Correlation of uptake of [111In]-FPI-1547 with biomarker results (e.g., immunohistochemistry (ICH) staining, [18F]-FDG Positron Emission Tomography (PET)). [ Time Frame: 4 weeks post final [225Ac]-FPI-1434 Injection. ]

Eligibility Criteria

• 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 which is ≥ 20 mm in largest diameter.
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 enrollment.
7. Adequate organ function as indicated by the following laboratory values (all laboratory tests must occur within 14 days before the first dose of study treatment):

8. 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)
9. 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 (except for patients with body mass index (BMI) > 30 kg/m2 when lean body weight should be used instead).

10. 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)
11. Other laboratory results, vital signs and ECGs are acceptable for enrollment (in the opinion of the Investigator).
12. Females of childbearing potential must have a negative pregnancy test results during the General and Imaging Screening Periods.
13. 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 28 days following the [111In]-FPI-1547 injection, and 5 months (for males) or 8 months (for females)following the final [225Ac]-FPI-1434 Injection.
14. Ability to understand and the willingness to sign a written informed consent document.
15. In the opinion of the Investigator, the patient is expected to be compliant and have a high probability of completing the study.
16. Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

Exclusion Criteria:

1. Received a 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 for the image acquisitions, etc.)

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

   a. To be eligible for the study treatment, patients must have stable disease ≥ 1 month, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and have CNS metastases well controlled by low-stable or decreasing dose of steriods, anti-epileptics, or other symptom-relieving medications.

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 tumors are permitted.
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 proteinuria (e.g. urinary dipstick analysis for proteins is 3+ [300 mg/dL or 4+ [1,000 mg/dL], or daily urinary protein excretion > 500 mg/dL).
10. Known or suspect 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 (random blood sugar during screening ≥250 mg/dL [≥ 13.9 mmol/L]), 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 (e.g. external radiation therapy to whole pelvis)

Contacts and Locations

Contacts

Contact: Nicole Soule; +1 (888) 506-4215; clinicaltrials@fusionpharma.com

Contact: Deborah Lloyd; +1 (888) 506 4215; clinicaltrials@fusionpharma.com

Locations

United States, California

City of Hope; Recruiting

Duarte, California, United States, 91010

United States, Massachusetts

Dana-Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

United States, Minnesota

Masonic Cancer Center, University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

United States, New York

Roswell Park Comprehensive Cancer Center; Active, not recruiting

Buffalo, New York, United States, 14203

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

United States, Pennsylvania

Hospital of the University of Pennsylvania; Recruiting

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Australia, South Australia

Royal Adelaide Hospital; Active, not recruiting

Adelaide, South Australia, Australia, 5000

Australia, Victoria

Austin Hospital; Recruiting

Heidelberg, Victoria, Australia, 3084

Canada, Ontario

Juravinski Cancer Center - Hamilton Health; Recruiting

Hamilton, Ontario, Canada, L8V 5C2

Princess Margaret Cancer Centre; 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; Recruiting

Québec City, Quebec, Canada, G1R 2J6

Sponsors and Collaborators

Fusion Pharmaceuticals Inc.

Investigators

• Study Director: Julia Kazakin, MD; Fusion Pharmaceuticals Inc.

More Information

• Responsible Party: Fusion Pharmaceuticals Inc.
• ClinicalTrials.gov Identifier: NCT03746431
• Other Study ID Numbers: FPX-01-01
• First Posted: November 19, 2018
• Last Update Posted: March 3, 2022
• Last Verified: March 2022

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

Keywords provided by Fusion Pharmaceuticals Inc.:

225-Ac Labelled Humanized Monoclonal Antibody Against IGF-1R; [225Ac]-FPI-1434; IGF-IR Targeted Alpha Therapeutic; IGF-IR Radioligand Therapy