A Study of [225Ac]-FPI-2059 in Adult Participants With Solid Tumours

Study Overview
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Brief Summary
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This is a first-in-human Phase 1 clinical trial designed to investigate the safety, tolerability, pharmacokinetics, and biodistribution of [225Ac]-FPI-2059 and [111In]-FPI-2058 in participants with neurotensin receptor 1 (NTSR1)-expressing solid tumours.

Detailed Description
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This is a first-in-human, Phase 1, non-randomized, multi-centre, open-label clinical trial designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics (PK) of [225Ac]-FPI-2059 and [111In]-FPI-2058, as well as the pharmacodynamics and preliminary anti-tumour activity of [225Ac]-FPI-2059 in participants with neurotensin receptor 1 (NTSR1)-expressing advanced, metastatic and/or recurrent solid tumours. The study will employ a 3+3 dose escalation design to identify the recommended phase 2 dose (RP2D) and regimen of [225Ac]-FPI-2059 administered intravenously every 56 days. After the RP2D for [225Ac]-FPI-2059 is determined, enrolment will continue into an expansion cohort, to confirm the safety and tolerability of the RP2D, as well as to identify any preliminary evidence of efficacy in selected NTSR1-expressing tumour types.

Official Title
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A Phase 1 Study of [225Ac]-FPI-2059 in Adult Participants With NTSR1-Expressing Advanced, Metastatic and/or Recurrent Solid Tumours

Conditions
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Pancreatic Ductal Adenocarcinoma (PDAC), Squamous Cell Carcinoma of Head and Neck, Colorectal Cancer, Gastric Cancer, Ewing Sarcoma, NTSR1 Expressing Solid Tumours, Neuroendocrine Differentiated (NED) Prostate Cancer

Intervention / Treatment
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* Drug: [225]-FPI-2059
* Drug: [111In]-FPI-2058


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Signed ICF prior to initiation of any study-specific procedures Histologically and/or cytologically confirmed solid tumor that is metastatic or locally advanced, inoperable, or recurrent. Solid tumors indications may include PDAC, CRC, NED prostate cancer, gastric cancer, SCCHN, and Ewing sarcoma. Disease that has progressed despite prior treatment, and for which additional effective standard therapy is not available or is contraindicated, not tolerable, or the patient refuses standard therapy Measurable disease per RECIST v.1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Sufficient target expression in at least one measurable lesion as determined by imaging following injection of [111In]-FPI-2058 Adequate organ function Tumor tissue (either archival within the last 24 months or fresh biopsy) Key Exclusion Criteria: Previous treatment with any radiopharmaceutical Contraindications to or inability to perform the imaging procedures required in this study Anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or investigational agents within certain amount of time prior to administration of the first dose of [111In]-FPI-2058 Radiation therapy (RT) within 28 days prior to the first dose of [111In]-FPI-2058 Patients with known CNS metastatic disease Concurrent severe and/or uncontrolled illness that would limit compliance with study requirements Known or suspected allergies or contraindication to the investigational treatment Received any type of vaccine within 30 days prior to the first dose of [111In]-FPI-2058

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 Dose Escalation<br> | Drug: [225]-FPI-2059<br>* [225Ac]-FPI-2059 is a targeted alpha therapeutic that consists of an NTSR1-targeting small molecule that is linked to Ac-225, an alpha particle emitting radionuclide. Participants will be dosed through IV administration every 56 days up to four cycles. The dose depends on cohort assignment. In the Dose Expansion arm, [225Ac]-FPI-2059 will be administered at the RP2D as determined in Phase 1 Dose Escalation.<br>Drug: [111In]-FPI-2058<br>* [111In]-FPI-2058 is an imaging agent that consists of an NTSR1-targeting small molecule linked to In-111.Participants will receive [111In]-FPI-2058 by IV Injection for imaging once during screening period. The dose is consistent across cohorts.<br>|
| Experimental: Phase 1 Dose Expansion<br> | Drug: [225]-FPI-2059<br>* [225Ac]-FPI-2059 is a targeted alpha therapeutic that consists of an NTSR1-targeting small molecule that is linked to Ac-225, an alpha particle emitting radionuclide. Participants will be dosed through IV administration every 56 days up to four cycles. The dose depends on cohort assignment. In the Dose Expansion arm, [225Ac]-FPI-2059 will be administered at the RP2D as determined in Phase 1 Dose Escalation.<br>Drug: [111In]-FPI-2058<br>* [111In]-FPI-2058 is an imaging agent that consists of an NTSR1-targeting small molecule linked to In-111.Participants will receive [111In]-FPI-2058 by IV Injection for imaging once during screening period. The dose is consistent across cohorts.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events to evaluate safety and tolerability of [225Ac]-FPI-2059 and [111In]-FPI-2058 |  | approximately 5 years post final administration | 
| Maximum tolerated dose (MTD) of [225Ac]-FPI-2059 |  | 56 days post administration | 
| Radiation dose of [111In]-FPI-2058 and [225Ac]-FPI-2059 to whole body, organs, and selected regions of interest |  | within 56 days of administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumor activity of [225Ac]-FPI-2059 regimen measured by response per RECIST v1.1 |  | approximately 5 years post final administration | 
| Tumor uptake of [111In]-FPI-2058 by evaluating SPECT/CT and planar images |  | within 56 days of administration | 
| Pharmacokinetics (PK) of [225Ac]-FPI-2059 and [111In]-FPI-2059 by measuring changes in clearance, AUC, Cmax, and half-life |  | approximately 36 days of final administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumor, FPI-2059, FPI-2058, Pancreas, Prostate, Neuroendocrine, Stomach cancer, Gastric, Ewing sarcoma, HNSCC, Squamous cell carcinoma, CRC, Colorectal, actinium, targeted alpha therapy, radiopharmaceuticals