Targeted Alpha Therapy With 225Actinium-Prostate Specific Membrane Antigen (PSMA)-I&T of Castration-resISTant Prostate Cancer (TATCIST). (TATCIST)

PSMA-directed Targeted Alpha Therapy With FPI-2265 (225Ac-PSMA-I&T) for the Treatment of Metastatic Castration-resISTant Prostate Cancer (TATCIST). A Phase II Clinical Trial.

The treatment regimen will consist of 4 doses of FPI-2265

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Castration Resistant Prostate Cancer
• Intervention / Treatment: Drug: FPI-2265

Detailed Description

The treatment regimen will consist of 4 doses of FPI-2265, administered at 8 ± 1 week intervals, with an initial activity of 100 kilobecquerel (kBq)/kg (±10%).

Additional doses will be administered at 100 kBq/kg (±10%) with the following exceptions:

• Participants who experience dose-modifying events.
• Participants with a confirmed decline in PSA>=50%.

• Study Type: Interventional
• Enrollment (Estimated): 115
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • XCancer Omaha/Urology Cancer Center
  • Texas
    • Houston, Texas, United States, 77042
      • Excel Diagnostics and Nuclear Oncology Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants aged ≥ 18 years.
2. Participants must have the ability to understand and sign an approved informed consent (ICF).
3. Participants must have the ability to understand and comply with all protocol requirements.
4. Adenocarcinoma of prostate proven by histopathology.
5. Life expectancy of 6 months or more.
6. Unresectable metastases.

7. Documented progressive disease (PD); progressive mCRPC will be based on at least 1 of the following criteria:

   1. Serum PSA progression is defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal starting value is 1.0 ng/mL, if PSA is the only indication of progression.
   2. Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions.
   3. Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 PCWG3 criteria).
8. If known Breast Cancer gene (BRCA) mutations are present, participants should have received FDA approved therapies such as poly-ADP ribose polymerase (PARP) inhibitors and progressed.
9. Castration resistant disease with confirmed testosterone level ≤ 50 ng/dL under prior androgen deprivation therapy (ADT). Must have a castrate level of serum testosterone (< 50 ng/dL or < 1.7 nmol/L).
10. Positive PSMA PET/CT scans, obtained with approved PSMA-ligands, defined as at least one PSMA-positive metastatic lesion and no PSMA-negative lesions.
11. ECOG-PS 0 to 1.
12. Hemoglobin (Hgb) concentration ≥ 9.0 g/dL.
13. Platelet counts ≥ 100 × 10^9/L.

14. White blood cell (WBC) count ≥ 2.0 × 10^9/L, absolute neutrophil count (ANC) > 1.5 × 10^9/L.

    a. Hematological criteria cannot be met with ongoing or recent blood transfusions (within 7 days prior to the scheduled first dose of study treatment) or require growth factor support (within 21 days prior to the scheduled first dose of study treatment).

15. Alanine aminotransferase or aspartate aminotransferase ≤ 3.0 × upper limit of normal (ULN).
16. Serum total bilirubin ≤ 1.5 × ULN; in participants with Gilbert's syndrome, a total bilirubin ≤ 3 times ULN and direct bilirubin within normal limits are permitted.
17. Albumin ≥ 2.5 g/dL.
18. Serum/plasma creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min based on the Cockcroft-Gault formula.
19. Prothrombin time, international normalized ratio or prothrombin time test < 1.5 × ULN.
20. Received ≥ 1 androgen receptor axis-targeted therapies (ARAT).
21. Participants on anti-androgen therapy are allowed to continue their treatment at the discretion of their treating physician.

Exclusion Criteria:

1. Less than 6 weeks from enrollment since last myelosuppressive therapy (including Docetaxel, Cabazitaxel, 223Ra, 153Sm, 177Lu-PSMA-617/other Lu-PSMA RLT or any other radionuclide therapy). Participants who received previous treatment with Ac-225 are excluded.
2. Participants who received more than 4 prior lines of systemic therapy for CRPC.
3. Urinary tract obstruction as evidenced by Tc-99m DTPA renal scan with diuretics.

4. Participants with skeletal metastases presenting as a superscan on a 99m Tc MDP Bone Scan.

   Superscan is defined as a bone scan which demonstrates markedly increased skeletal radioisotope uptake relative to soft tissues in association with absent or faint renal activity (absent kidney sign).

5. Persistent baseline dry eye or dry mouth > Grade 1 from prior RLT.
6. Persistent prior AEs > Grade 1 from prior anti-cancer therapies.
7. Abnormal renal function (estimated glomerular filtration rate < 60 mL/min), baseline Hgb < 9g/dL, ANC < 1.5 ×10^9/L, platelets < 100 ×10^9/L, and prothrombin time, international normalized ratio or prothrombin time test ≥ 1.5 × ULN.
8. Administration of an investigational agent ≤ 60 days or 5 half-lives, whichever is shorter, prior to Cycle 1, Week 0.
9. Known presence of central nervous system (CNS) metastases or liver metastases.
10. Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer.
11. Concurrent illness that may jeopardize the participant's ability to undergo study procedures as determined by the Investigator.
12. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
13. Concurrent serious (as determined by the investigator) medical conditions, including, but not limited to, New York Heart Association Class III or IV congestive heart failure, unstable ischemia, uncontrolled symptomatic arrhythmia, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the Investigator would impair study participation or cooperation.
14. Major surgery ≤ 30 days prior to enrollment.
15. Planning to conceive pregnancy during the treatment and up to 6 months after the last treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FPI-2265; All patients will receive FPI-2265, administered at 8 ± 1-week interval, with the initial activity of 100 kBq/kg (±10%).	Drug: FPI-2265; Small molecule capable of binding to the domain of PSMA radiolabeled with Ac225; Other Names: Ac225-PSMA I&T

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effect of FPI-2265 on prostate-specific antigen (PSA) in participants with mCRPC.	Frequency and proportion of participants with PSA50, defined as ≥ 50% decline in PSA level by 12-weeks after the first treatment.	From start of treatment until 12 weeks after the first treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety and tolerability of FPI- 2265.	Frequency, duration and severity of treatment emergent adverse events (TEAEs) evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0).; Changes in clinical laboratory, electrocardiograms (ECGs) and physical examinations compared to baseline.	From first treatment dose to up to 24 months after last treatment.
To evaluate the anti-tumor activity of FPI-2265.	Maximum % PSA decline.; PSA progression free survival (PFS).; Time to best PSA response; Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).; Disease control rate (DCR) per RECIST v1.1.; Duration of response (DoR) based on RECIST v1.1/Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria.; Radiographic progression-free survival (rPFS) per PCWG3 criteria.; Overall survival (OS).	From first treatment until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 24 months after last treatment.
To assess the impact of FPI-2265 on participant reported outcomes.	The frequency and proportion of participants with an improvement in bone pain levels.; Change in quality of life (QoL) over time.	From first treatment until 24 months after last treatment.

Collaborators and Investigators

• Sponsor: Fusion Pharmaceuticals Inc.
• Investigators: Study Director: Keith Barnett, Fusion Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Actual): May 30, 2025
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: December 20, 2021
• First Submitted That Met QC Criteria: January 27, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: FPI-2265-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No