100 Participants Needed

FPI-2265 for Metastatic Prostate Cancer

(AlphaBreak Trial)

Recruiting at 17 trial locations
CT
Overseen ByClinical Trials Fusion Pharmaceuticals Inc.
Age: 18+
Sex: Male
Trial Phase: Phase 2 & 3
Sponsor: Fusion Pharmaceuticals Inc.
Must be taking: Androgen-deprivation therapy
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This is an open-label, randomized, multicenter study of FPI-2265 (225Ac-PSMA-I\&T). Patient population is adult participants with PSMA positive mCRPC who have had previous treatment with with 177Lu-PSMA-617 or another 177Lu-PSMA radioconjugate (RC). The purpose of the study is to determine the safety and tolerability, and recommended dose and regiment of FPI-2265.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had any systemic cytotoxic or investigational therapy within 30 days before the first dose of the study treatment.

What data supports the effectiveness of the drug FPI-2265 for metastatic prostate cancer?

Research shows that similar treatments using 225Ac-PSMA, like 225Ac-PSMA-617, have been effective in reducing symptoms and imaging lesions in patients with metastatic prostate cancer, with some patients experiencing no adverse effects.12345

What safety data exists for FPI-2265 (225Ac-PSMA-I&T) in humans?

In a study with 14 patients using 225Ac-PSMA-I&T for advanced prostate cancer, no acute toxicity was observed during treatment. Some patients experienced side effects like anemia (low red blood cell count) and leukopenia (low white blood cell count), but these were generally manageable. Additionally, mild to moderate dry mouth was noted in some patients.56789

What makes the drug FPI-2265 unique for treating metastatic prostate cancer?

FPI-2265 (225Ac-PSMA-I&T) is unique because it uses targeted alpha therapy (TAT) to deliver alpha-particle radiation directly to prostate cancer cells that express PSMA (prostate-specific membrane antigen), which can be effective even when other treatments have failed. This approach is promising for patients with advanced metastatic castration-resistant prostate cancer, especially those who have not responded to or have developed resistance to other therapies like 177Lu-PSMA.2361011

Research Team

KB

Keith Barnett

Principal Investigator

Fusion Pharmaceuticals Inc.

Eligibility Criteria

This trial is for individuals with metastatic castration-resistant prostate cancer (mCRPC) that shows PSMA positivity. Participants must have previously undergone treatment with a specific type of radioligand therapy using 177Lu-PSMA.

Inclusion Criteria

My prostate cancer is worsening despite treatment.
My prostate cancer was confirmed through a tissue examination.
Ability to understand and sign an approved informed consent form (ICF) and comply with all protocol requirements
See 7 more

Exclusion Criteria

I have had more than two chemotherapy treatments for prostate cancer.
Concurrent serious (as determined by the investigator) medical conditions
I have not had major surgery in the last 30 days.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FPI-2265 in one of three dosing regimens: Arm 1 (9 doses every 4 weeks), Arm 2 (6 doses every 6 weeks), or Arm 3 (4 doses every 8 weeks)

16-32 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of PSA50 response and adverse events

12 weeks

Long-term follow-up

Participants are monitored for long-term safety and efficacy, including treatment-emergent adverse events

5 years

Treatment Details

Interventions

  • FPI-2265 (225Ac-PSMA-I&T)
Trial OverviewThe study is testing FPI-2265, a new drug targeting PSMA-positive cells in mCRPC patients. It's an open-label and multicenter trial aiming to find the best dose by looking at safety, tolerability, and how well it works against tumors.
Participant Groups
7Treatment groups
Experimental Treatment
Group I: Part B Arm 7Experimental Treatment1 Intervention
Group II: Part B Arm 6Experimental Treatment1 Intervention
Group III: Part B Arm 5Experimental Treatment1 Intervention
to be utilized based on analysis of Part A
Group IV: Part B Arm 4Experimental Treatment1 Intervention
to be utilized based on analysis of Part A
Group V: Part A Arm 3Experimental Treatment1 Intervention
Group VI: Part A Arm 2Experimental Treatment1 Intervention
Group VII: Part A Arm 1Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Fusion Pharmaceuticals Inc.

Lead Sponsor

Trials
6
Recruited
590+

Findings from Research

In a systematic review of 141 patients with metastatic castration-resistant prostate cancer (mCRPC), 225 Ac-PSMA-targeted alpha therapy (TAT) showed a significant biochemical response, with 83% of patients experiencing any decline in prostate-specific antigen (PSA) levels and 59% achieving more than a 50% decline.
The treatment also demonstrated promising overall survival rates of 81% and a median progression-free survival of 12 months, while maintaining low toxicity, with the most common side effects being mild dry mouth and fatigue.
225 Ac-PSMA-617-targeted alpha therapy for the treatment of metastatic castration-resistant prostate cancer: A systematic review and meta-analysis.Ballal, S., Yadav, MP., Sahoo, RK., et al.[2021]
A case study demonstrated that 225 Ac-PSMA-617 therapy led to remission of clinical symptoms and imaging lesions in a patient with metastatic castration-resistant prostate cancer after 4 treatment cycles.
The patient experienced no observable adverse effects, suggesting that 225 Ac-PSMA-617 may be a safe and effective alternative for those who do not respond to 177 Lu-PSMA therapy.
Treatment of Multiple Bone Metastases of Castration-Resistant Prostate Cancer With 225 Ac-PSMA-617.Yang, H., Zhang, Y., Su, D., et al.[2023]
In a study of 12 patients with metastatic castration-resistant prostate cancer, 225Ac-PSMA therapy showed promising results, with 9 out of 12 patients exhibiting a PSA response after the first treatment cycle, and 6 achieving a significant reduction of over 50%.
The median overall survival for patients who responded to the therapy was 10 months, compared to 4 months for non-responders, suggesting that early PSA response may correlate with better survival outcomes, although the difference was not statistically significant.
225Ac-Prostate-Specific Membrane Antigen Therapy for Castration-Resistant Prostate Cancer: A Single-Center Experience.Sanli, Y., Kuyumcu, S., Simsek, DH., et al.[2023]

References

225 Ac-PSMA-617-targeted alpha therapy for the treatment of metastatic castration-resistant prostate cancer: A systematic review and meta-analysis. [2021]
Treatment of Multiple Bone Metastases of Castration-Resistant Prostate Cancer With 225 Ac-PSMA-617. [2023]
225Ac-Prostate-Specific Membrane Antigen Therapy for Castration-Resistant Prostate Cancer: A Single-Center Experience. [2023]
68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies. [2018]
Prostate-Specific Membrane Antigen-Targeting Alpha Emitter via Antibody Delivery for Metastatic Castration-Resistant Prostate Cancer: A Phase I Dose-Escalation Study of 225Ac-J591. [2023]
First Clinical Results for PSMA-Targeted α-Therapy Using 225Ac-PSMA-I&T in Advanced-mCRPC Patients. [2021]
Preclinical Evaluation of 213Bi- and 225Ac-Labeled Low-Molecular-Weight Compounds for Radiopharmaceutical Therapy of Prostate Cancer. [2022]
Prostate specific membrane antigen binding radiopharmaceuticals: Current data and new concepts. [2022]
99mTc-labeled PSMA inhibitor: Biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients. [2018]
Long-term survival outcomes of salvage [225Ac]Ac-PSMA-617 targeted alpha therapy in patients with PSMA-expressing end-stage metastatic castration-resistant prostate cancer: a real-world study. [2023]
11.United Arab Emiratespubmed.ncbi.nlm.nih.gov
An Overview of Targeted Alpha Therapy with 225Actinium and 213Bismuth. [2019]