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

NCT05219500 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: FPI-2265-201
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Metastatic Castration Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• To evaluate the safety and tolerability of FPI- 2265.

  From first treatment dose to up to 24 months after last treatment.

• To evaluate the anti-tumor activity of FPI-2265.

  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.

  From first treatment until 24 months after last treatment.

Study Arms (1)

FPI-2265

EXPERIMENTAL

All patients will receive FPI-2265, administered at 8 ± 1-week interval, with the initial activity of 100 kBq/kg (±10%).

Drug: FPI-2265

Interventions

FPI-2265 DRUG

Small molecule capable of binding to the domain of PSMA radiolabeled with Ac225

Also known as: Ac225-PSMA I&T

FPI-2265

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants aged ≥ 18 years.
• Participants must have the ability to understand and sign an approved informed consent (ICF).
• Participants must have the ability to understand and comply with all protocol requirements.
• Adenocarcinoma of prostate proven by histopathology.
• Life expectancy of 6 months or more.
• Unresectable metastases.
• Documented progressive disease (PD); progressive mCRPC will be based on at least 1 of the following criteria:
• 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.
• 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.
• Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 PCWG3 criteria).
• 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.
• 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).
• Positive PSMA PET/CT scans, obtained with approved PSMA-ligands, defined as at least one PSMA-positive metastatic lesion and no PSMA-negative lesions.
• ECOG-PS 0 to 1.
• Hemoglobin (Hgb) concentration ≥ 9.0 g/dL.

You may not qualify if:

• 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.
• Participants who received more than 4 prior lines of systemic therapy for CRPC.
• Urinary tract obstruction as evidenced by Tc-99m DTPA renal scan with diuretics.
• 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).
• Persistent baseline dry eye or dry mouth \> Grade 1 from prior RLT.
• Persistent prior AEs \> Grade 1 from prior anti-cancer therapies.
• 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.
• Administration of an investigational agent ≤ 60 days or 5 half-lives, whichever is shorter, prior to Cycle 1, Week 0.
• Known presence of central nervous system (CNS) metastases or liver metastases.
• Active malignancy other than low-grade non-muscle-invasive bladder cancer and non-melanoma skin cancer.
• Concurrent illness that may jeopardize the participant's ability to undergo study procedures as determined by the Investigator.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
• 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.
• Major surgery ≤ 30 days prior to enrollment.

Sponsors & Collaborators

• Fusion Pharmaceuticals Inc.: lead

Study Sites (2)

XCancer Omaha/Urology Cancer Center

Omaha, Nebraska, 68130, United States

Location

Excel Diagnostics and Nuclear Oncology Center

Houston, Texas, 77042, United States

Location

Study Officials

• Keith Barnett

  Fusion Pharmaceuticals Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: February 2, 2022
• Study Start: December 16, 2021
• Primary Completion: May 30, 2025
• Study Completion (Estimated): July 31, 2026
• Last Updated: October 8, 2025

Record last verified: 2025-02

Locations

US (2)