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

• ClinicalTrials.gov Identifier: NCT05605522
• Recruitment Status: Recruiting
• First Posted: November 4, 2022
• Last Update Posted: April 5, 2024
• Sponsor: Fusion Pharmaceuticals Inc.
• Information provided by (Responsible Party): Fusion Pharmaceuticals Inc.

Tracking Information

• First Submitted Date: October 31, 2022
• First Posted Date: November 4, 2022
• Last Update Posted Date: April 5, 2024
• Actual Study Start Date: February 7, 2023
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 31, 2022)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 31, 2022)

• Anti-tumor activity of [225Ac]-FPI-2059 regimen measured by response per RECIST v1.1 [ Time Frame: approximately 5 years post final administration ]
• Tumor uptake of [111In]-FPI-2058 by evaluating SPECT/CT and planar images [ Time Frame: 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 [ Time Frame: approximately 36 days of final administration ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

• 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.

• Drug: [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.

Study Arms

• Experimental: Phase 1 Dose Escalation
  Interventions:

  • Drug: [225]-FPI-2059
  • Drug: [111In]-FPI-2058
• Experimental: Phase 1 Dose Expansion
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 31, 2022): 42
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2025
• Estimated Primary Completion Date: June 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trials Fusion Pharmaceuticals; 1 (888) 506-4215; clinicaltrials@fusionpharma.com

• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT05605522
• Other Study ID Numbers: FPI-2059-101
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fusion Pharmaceuticals Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Fusion Pharmaceuticals Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Joanne Schindler, MD, DVM; Fusion Pharmaceuticals Inc.

• PRS Account: Fusion Pharmaceuticals Inc.
• Verification Date: April 2024