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

Protocol # :
Advanced Solid Tumours
Endometrial Cancer
Cervical Cancer
Ovarian Cancer
Breast Cancer
Triple Negative Breast Cancer (TNBC)
HER2-negative Breast Cancer
Head and Neck Squamous Cell Carcinoma (HNSCC)
Adrenocortical Carcinoma
Uveal Melanoma
Disease Sites
Gastroesophageal Junction
Lip, Oral Cavity and Pharynx
Small Intestine
Other Digestive Organ
Other Respiratory and Intrathoracic Organs
Bones and Joints
Soft Tissue
Mycosis Fungoides
Other Skin
Corpus Uteri
Other Female Genital
Other Male Genital
Urinary Bladder
Other Urinary
Eye and Orbit
Brain and Nervous System
Unknown Sites
Ill-Defined Sites
Other Endocrine System
Kaposi's Sarcoma
Melanoma, Skin
Principal Investigator
Jacene, Heather, Alison
Site Research Nurses
Baylies, Rosemarie
Carey, Margaret, M.
DeGonge, Danielle
Gillen Mckay, Christine, A.
Harran, John
Hedglin, Jennifer
Powers, Allison
Rang, Bethany
Rowan, Jennifer, M.

Trial Description

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).

Eligibility Requirements

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

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

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