A Phase 1/2 Study of [225Ac]-FPI-1434 Injection in Patients with Locally Advanced or Metastatic Solid Tumours


The study consists of a Phase 1 dose-escalation portion (including both single and multi-dosing cohorts), a Cold Antibody Sub-Study, and a Phase 2. This is a Phase 1/2 clinical trial of a therapeutic investigational drug called [225Ac]-FPI-1434 to investigate safety, tolerability, pharmacokinetics, and anti-tumor activity. The study uses two additional investigational products: • [111In]-FPI-1547 Injection (imaging agent) • FPI-1175 Infusion (cold antibody)

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18 Years and over
This study is NOT accepting healthy volunteers
Inclusion Criteria:

• Age ≥18 years old.
• 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.
• At least 1 measurable lesion which is ≥ 20 mm in largest diameter.
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1.
• Life expectancy of greater than 3 months as judged by the treating physician.
• Available tumour tissue (either archival or fresh biopsy) for IGF-1R immunohistochemistry. Submission of the tissue is not required prior to enrollment.
• 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):
• Adequate bone marrow reserves without the use of hematopoietic growth factors, red cell or platelet transfusion as evidenced by:
• Absolute neutrophil count ≥ 1,500/ mm^3 (≥ 1.5 x 10^9/L)
• Platelet count ≥ 100,000/ mm^3 (≥ 100 x 10^9/L)
• Hemoglobin ≥ 9 g/dL (≥ 90 g/L)
• 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).
• Adequate hepatic function as evidenced by:
• Serum total bilirubin ≤ 1.5x upper limit of normal (ULN), unless patient has Gilbert's disease
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN in patients with known liver metastasis)
• Other laboratory results, vital signs and ECGs are acceptable for enrollment (in the opinion of the Investigator).
• Females of childbearing potential must have a negative pregnancy test results during the General and Imaging Screening Periods.
• 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.
• Ability to understand and the willingness to sign a written informed consent document.
• In the opinion of the Investigator, the patient is expected to be compliant and have a high probability of completing the study.
• 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:

• Received a systemic therapeutic radiopharmaceutical within 6 months prior to enrollment into this study.
• Contraindications to or inability to perform the required imaging procedures in this study (e.g. inability to lay flat for the image acquisitions, etc.)
• 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.
• 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.
• 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.
• Residual CTCAE ≥ Grade 2 side effects of prior therapy, with the exception of residual grade 2 alopecia.
• Prior organ transplantation, including stem cell transplantation.
• Any prior treatment with nitrosoureas or actinomycin-D.
• 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).
• Known or suspect allergies or contraindications to the Investigational Products or any component of the investigational drug formulation.
• 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.
• Received > 20 Gy prior radiation to large areas of the bone marrow (e.g. external radiation therapy to whole pelvis)

Drug: [111In]-FPI-1547 Injection, Drug: [225Ac]-FPI-1434 Injection multi-dose, Biological: FPI-1175 Infusion, Drug: [225Ac]-FPI-1434 Injection single-dose

Advanced Solid Tumours, Actinium-225, Antineoplastic Agents, Targeted Alpha Therapy, Radioimmunoconjugate

225-Ac Labelled Humanized Monoclonal Antibody Against IGF-1R, [225Ac]-FPI-1434, IGF-IR Targeted Alpha Therapeutic, IGF-IR Radioligand Therapy, Clinics and Surgery Center (CSC), Phase I Clinic

Douglas Yee -
Douglas Yee, MD
Phase 1/Phase 2
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