Ac225-PSMA I&T for Prostate Cancer

(TATCIST Trial)

Not currently recruiting at 1 trial location

Overseen By Clinical Trials Fusion Pharmaceuticals Inc.

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Fusion Pharmaceuticals Inc.

Must be taking: Anti-androgens

Must not be taking: Radionuclide therapy

Disqualifiers: CNS metastases, Liver metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 32 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Ac225-PSMA I&T for prostate cancer that has spread and does not respond to standard hormone therapy. It focuses on patients with ongoing cancer despite treatments and visible signs of progression, such as increasing PSA levels or bone metastasis. The treatment involves administering specific doses every two months to determine if it can control the cancer more effectively than current options. Suitable candidates include those with biopsy-confirmed prostate cancer, who have tried other treatments, and have a life expectancy of at least six months. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop your current medications. However, participants on anti-androgen therapy are allowed to continue their treatment at the discretion of their treating physician.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does allow participants on anti-androgen therapy to continue their treatment with their doctor's approval.

Is there any evidence suggesting that Ac225-PSMA I&T is likely to be safe for humans?

Research has shown that the treatment Ac225-PSMA I&T has been tested for safety in prostate cancer patients. One study focused on its use in patients with metastatic castration-resistant prostate cancer, an advanced form of the disease. The results indicated that the treatment could be used safely, with generally tolerable side effects.

Another study examined the safety and long-term effects of this treatment. It found that while some patients experienced side effects, these were usually manageable. The study aimed to determine the best dose to minimize these effects while effectively treating the cancer.

Overall, previous patients demonstrated that Ac225-PSMA I&T can be safely used to treat advanced prostate cancer, although it may have some side effects, like many treatments. This is important to consider when thinking about joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ac225-PSMA I&T is unique because it uses a targeted approach to treat prostate cancer by delivering a radioactive particle directly to cancer cells. Unlike traditional treatments like chemotherapy or hormone therapy, which affect the entire body, Ac225-PSMA I&T specifically targets the PSMA protein found on the surface of prostate cancer cells. This precision allows for potentially fewer side effects and more effective treatment of cancerous cells. Researchers are excited about this because it represents a shift towards personalized cancer therapy, offering hope for improved outcomes in patients with advanced prostate cancer.

What evidence suggests that Ac225-PSMA I&T might be an effective treatment for prostate cancer?

Research shows that Ac225-PSMA I&T holds promise for treating advanced prostate cancer that has spread and resists standard hormone treatments. It can shrink or slow the cancer by specifically targeting cancer cells, potentially resulting in fewer side effects than traditional treatments. Studies have found this treatment both safe and effective, aiding patients in better managing their cancer. Overall, evidence suggests it could offer significant benefits for prostate cancer patients. ^{2 3 4 5 6}

Who Is on the Research Team?

Keith Barnett

Principal Investigator

Fusion Pharmaceuticals Inc.

Are You a Good Fit for This Trial?

This trial is for men with advanced prostate cancer that can't be removed, has spread, and isn't responding to certain therapies like docetaxel. Participants must understand the study, sign consent, have a life expectancy of at least 6 months, and meet specific health criteria including blood counts and organ function tests.

Inclusion Criteria

I have received at least one therapy targeting the androgen receptor.

Life expectancy of 6 months or more

Documented progressive disease (PD)

Exclusion Criteria

Administration of an investigational agent within specified timeframe

My kidney function and blood tests are not within normal ranges.

I am experiencing symptoms due to spinal cord pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 4 doses of FPI-2265, administered at 8 ± 1 week intervals

32 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Ac225-PSMA I&T

Trial Overview The TATCIST trial is testing a treatment called Ac225-PSMA I&T in men with castration-resistant prostate cancer. It involves four doses of this targeted alpha therapy which seeks out cancer cells using a molecule that binds to PSMA receptors on tumor cells.

How Is the Trial Designed?

Group I: FPI-2265 Experimental Treatment 1 Intervention

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

Ac225-PSMA I&T is already approved in European Union, United States for the following indications:

Approved in European Union as 225Ac-PSMA I&T for:

• Metastatic castration-resistant prostate cancer

Approved in United States as 225Ac-PSMA I&T for:

• Advanced metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Fusion Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

590+

Excel Diagnostics and Nuclear Oncology Center

Lead Sponsor

Trials

6

Recruited

660+

Published Research Related to This Trial

In a study of 14 patients with advanced metastatic castration-resistant prostate cancer, treatment with 225Ac-PSMA imaging and therapy (I&T) showed promising results, with 50% or greater declines in prostate-specific antigen (PSA) levels observed in 7 patients.

The treatment was well-tolerated, with no acute toxicity during hospitalization, although some patients experienced grade 3 anemia and leukopenia; importantly, preexisting xerostomia did not worsen in most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Clinical Results for PSMA-Targeted α-Therapy Using 225Ac-PSMA-I&T in Advanced-mCRPC Patients. Zacherl, MJ., Gildehaus, FJ., Mittlmeier, L., et al.[2021]

Actinium-225 (Ac-225) PSMA radioligand therapy (RLT) shows promising efficacy in treating metastatic castration-resistant prostate cancer (mCRPC), with 81% of patients experiencing a decline in PSA levels and 60% achieving more than a 50% reduction.

The treatment is generally safe, with the most common side effect being mild to moderate xerostomia (dry mouth) reported in 73.9% of patients, indicating that Ac-225 may have fewer severe side effects compared to traditional beta-emitting therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Actinium-225 Prostate-Specific Membrane Antigen Radioligand Therapy in Metastatic Prostate Cancer: A Systematic Review and Metanalysis. Parida, GK., Panda, RA., Bishnoi, K., et al.[2023]

The study successfully manufactured [225Ac]Ac-PSMA-I&T, a promising treatment for metastatic castration-resistant prostate cancer, adhering to good manufacturing practice guidelines, which is crucial for its upcoming clinical phase 1 dose escalation study.

The final product demonstrated high radiochemical yield (>95%) and purity (>90%), ensuring its quality and safety for patient use, with optimized conditions for effective delivery of the alpha emitter Ac-225 to target PSMA-positive cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of [225Ac]Ac-PSMA-I&T for Targeted Alpha Therapy According to GMP Guidelines for Treatment of mCRPC. Hooijman, EL., Chalashkan, Y., Ling, SW., et al.[2021]

In a study of 23 patients with advanced-stage metastatic castration-resistant prostate cancer (mCRPC) who were unresponsive to [177Lu]Lu-PSMA therapy, [225Ac]Ac-PSMA treatment demonstrated a safety profile with manageable side effects, including some cases of grade 3 hematologic and nephrotoxicity.

The treatment showed potential efficacy, with 26% of patients achieving a significant decline in prostate-specific antigen (PSA) levels and a disease control rate of 50%, indicating that [225Ac]Ac-PSMA could be a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Experience with [225Ac]Ac-PSMA Treatment in Patients with [177Lu]Lu-PSMA-Refractory Metastatic Castration-Resistant Prostate Cancer. Alan-Selcuk, N., Beydagi, G., Demirci, E., et al.[2023]

In a study of 56 patients with metastatic castration-resistant prostate cancer (mCRPC) who had exhausted standard treatments, [225Ac]Ac-PSMA-617 targeted alpha therapy showed promising efficacy, with 91% of patients experiencing a decline in prostate-specific antigen (PSA) levels, and a median overall survival of 15 months.

The treatment was well-tolerated, with most adverse events being mild to moderate, such as transient fatigue in 70% of patients and xerostomia in about one-third, indicating that [225Ac]Ac-PSMA-617 could be a viable option for patients with advanced mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Ballal, S., Yadav, MP., Satapathy, S., et al.[2023]

The study found that actinium-225 labeled PSMA-specific tracers ([225Ac]Ac-PSMA-I&T) have a significantly higher relative biological effectiveness (RBE) of 4.2 times compared to lutetium-177 labeled tracers ([177Lu]Lu-PSMA-I&T), suggesting that actinium-225 may provide a more effective treatment for prostate cancer due to its ability to induce more complex DNA damage.

Both tracers showed similar binding characteristics to prostate cancer cells, but [225Ac]Ac-PSMA-I&T resulted in slower DNA double strand break repair kinetics, indicating that the type of radiation emitted by actinium-225 leads to more challenging DNA damage compared to lutetium-177.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro dose effect relationships of actinium-225- and lutetium-177-labeled PSMA-I&T. Ruigrok, EAM., Tamborino, G., de Blois, E., et al.[2022]

177Lu-PSMA is an effective treatment for advanced prostate cancer, lowering PSA levels and improving quality of life, but about one-third of patients may not respond well to this therapy, highlighting the need for better personalization of treatment.

225Ac-PSMA shows promise for tumors resistant to standard treatments, offering a better response than 177Lu-PSMA, but it poses risks of significant damage to healthy tissues, necessitating careful dosimetry and potential use of nano-carriers for safer delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of 177Lutetium-PSMA and 225Actinium-PSMA as Emerging Theranostic Agents in Prostate Cancer. Alam, MR., Singh, SB., Thapaliya, S., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38287346/

Evaluation of the tolerability and safety of [225Ac]Ac-PSMA ... This trial will assess the safety and tolerability of 225 Ac-PSMA-I&T in patients with mCRPC to recommend the optimal dose for the phase II trial.

2. jnm.snmjournals.org jnm.snmjournals.org/content/62/5/669

First Clinical Results for PSMA-Targeted α-Therapy Using 225 ... Our first clinical data for TAT using 225 Ac-PSMA-I&T showed a promising antitumor effect in advanced metastatic castration-resistant prostate cancer.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS282

ACCEL: [Ac-225]-PSMA-62 phase Ia/Ib/II clinical trial to ... A multi-center, open-label, multiple-arm, Phase Ia/Ib/II study evaluating the safety, tolerability, and efficacy of [Ac-225]-PSMA-62 in patients with ...

4. mdpi.com mdpi.com/2072-6694/17/3/405

Long-Term Safety and Survival Outcomes of [ 225 Ac] ... This study investigates the safety of Radioligand Therapy with 225 Ac-Ac-PSMA in patients with metastatic castration-resistant prostate cancer.

5. urotoday.com urotoday.com/conference-highlights/2025-ucsf-ucla-psma-conference/159337-psma-and-beyond-2025-ac225-psma-experience.html

PSMA and Beyond 2025: Ac225 PSMA Experience 225 Ac-PSMA for therapy of prostate cancer is a success story for targeted alpha therapy, with the following developmental timeline.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10601660/

Efficacy and Safety of Actinium-225 Prostate-Specific ... This systematic review with meta-analysis is focused on the therapeutic responses, survival effects, and significant side effects of 225Ac-PSMA RLT in mCRPC.