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

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).

This study consists of a Phase 1 portion and a Phase 2 portion.

Phase 1 includes the following cohorts: Single dose-ascending cohorts and Multi- dose ascending cohorts of \[225Ac\]-FPI-1434 and Multi- dose ascending cohorts evaluating administration of FPI-1175 (cold antibody), followed by, \[225Ac\]-FPI-1434 (cold + hot), with cycles repeating every 42 days. And Cold Antibody Sub-study evaluating administration of ascending doses of FPI-1175 followed by \[111In\]-FPI-1547.

The Phase 2 will evaluate \[111In\]-FPI-1547 and \[225Ac\]-FPI-1434 with or without FPI-1175 in tumour-specific cohorts. The decision to utilize FPI-1175 in the Phase 2 portion of the study will be determined based on Phase 1 data, including safety, tolerability, pharmacokinetic and dosimetry results.

Eligibility Criteria:
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.

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