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

Phase 1

Recruiting

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

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
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
Incidence of Adverse Events to evaluate safety and tolerability of [225Ac]-FPI-2059 and [111In]-FPI-2058	approximately 5 years post final administration

Secondary Outcome Measures

Name	Time	Method
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
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

Locations (8): Hoag Family Cancer Institute
🇺🇸
Newport Beach, California, United States
Westmead Hospital
🇦🇺
Sydney, New South Wales, Australia
University of Alabama at Birmingham Hospital
🇺🇸
Birmingham, Alabama, United States
XCancer Omaha / Urology Cancer Center
🇺🇸
Omaha, Nebraska, United States
University of Kentucky
🇺🇸
Lexington, Kentucky, United States
City of Hope Medical Center
🇺🇸
Duarte, California, United States
Advanced Molecular Imaging and Therapy
🇺🇸
Glen Burnie, Maryland, United States
Washington University
🇺🇸
Saint Louis, Missouri, United States