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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05605522
• Other study ID #: FPI-2059-101
• Status: Recruiting
• Phase: Phase 1
• Start date: February 7, 2023
• Est. completion date: September 2025

Study information

• Verified date: April 2024
• Source: Fusion Pharmaceuticals Inc.
• Contact: Clinical Trials Fusion Pharmaceuticals
• Phone: 1 (888) 506-4215
• Email: clinicaltrials[@]fusionpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: September 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Colorectal Cancer
• Ewing Sarcoma
• Gastric Cancer
• Pancreatic Ductal Adenocarcinoma (PDAC)
• Sarcoma
• Sarcoma, Ewing
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• [225]-FPI-2059
[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.
• [111In]-FPI-2058
[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.

Locations

Country	Name	City	State
Australia	Westmead Hospital	Sydney	New South Wales
United States	University of Alabama at Birmingham Hospital	Birmingham	Alabama
United States	City of Hope Medical Center	Duarte	California
United States	Advanced Molecular Imaging and Therapy	Glen Burnie	Maryland
United States	University of Kentucky	Lexington	Kentucky
United States	Hoag Family Cancer Institute	Newport Beach	California
United States	XCancer Omaha / Urology Cancer Center	Omaha	Nebraska
United States	Washington University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Fusion Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events to evaluate safety and tolerability of [225Ac]-FPI-2059 and [111In]-FPI-2058		approximately 5 years post final administration
Primary	Maximum tolerated dose (MTD) of [225Ac]-FPI-2059		56 days post administration
Primary	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	Anti-tumor activity of [225Ac]-FPI-2059 regimen measured by response per RECIST v1.1		approximately 5 years post final administration
Secondary	Tumor uptake of [111In]-FPI-2058 by evaluating SPECT/CT and planar images		within 56 days of administration
Secondary	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

External Links

•   Sponsor Website