Clinical trial NCT05605522: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: 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
Keywords: 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
Lead sponsor: Fusion Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-04
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of Adverse Events to evaluate safety and tolerability of [225Ac]-FPI-2059 and [111In]-FPI-2058
timeFrame: approximately 5 years post final administration
measure: Maximum tolerated dose (MTD) of [225Ac]-FPI-2059
timeFrame: 56 days post administration
measure: Radiation dose of [111In]-FPI-2058 and [225Ac]-FPI-2059 to whole body, organs, and selected regions of interest
timeFrame: within 56 days of administration
Secondary outcomes:
measure: Anti-tumor activity of [225Ac]-FPI-2059 regimen measured by response per RECIST v1.1
timeFrame: approximately 5 years post final administration
measure: Tumor uptake of [111In]-FPI-2058 by evaluating SPECT/CT and planar images
timeFrame: within 56 days of administration
measure: Pharmacokinetics (PK) of [225Ac]-FPI-2059 and [111In]-FPI-2059 by measuring changes in clearance, AUC, Cmax, and half-life
timeFrame: approximately 36 days of final administration
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Hospital
state: Alabama
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Family Cancer Institute
state: California
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Glen Burnie
country: United States
facility: Advanced Molecular Imaging and Therapy
state: Maryland
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: XCancer Omaha / Urology Cancer Center
state: Nebraska
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
Study officials:
affiliation: Fusion Pharmaceuticals Inc.
name: Joanne Schindler, MD, DVM
role: STUDY_DIRECTOR
References: