Ac225-PSMA I&T for Prostate Cancer

(TATCIST Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Fusion Pharmaceuticals Inc.

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial involves giving patients FPI-2265 in specific amounts. The amounts may be adjusted based on how the patients respond to the treatment.

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.

What data supports the idea that Ac225-PSMA I&T for Prostate Cancer is an effective treatment?

The available research shows that Ac225-PSMA I&T is an effective treatment for prostate cancer, especially in advanced cases where other treatments have failed. In one study, 7 out of 14 patients experienced a significant reduction in prostate-specific antigen (PSA) levels, which is a marker used to track prostate cancer. Another study found that 58% of patients had some level of PSA decline after treatment. Compared to another treatment using Lutetium-177, Ac225-PSMA I&T is expected to have higher effectiveness and fewer side effects. This suggests that Ac225-PSMA I&T could be a promising option for patients with advanced prostate cancer. ^{1 2 3 4 5}

What safety data is available for Ac225-PSMA I&T in prostate cancer treatment?

The safety data for Ac225-PSMA I&T in prostate cancer treatment includes findings from several studies. In a clinical study involving 14 patients with advanced metastatic castration-resistant prostate cancer, no acute toxicity was observed during hospitalization. However, some side effects were recorded: grade 3 anemia in 3 patients, grade 3 leukopenia in 1 patient, and newly diagnosed grade 1 or 2 xerostomia in 5 patients. A systematic review and meta-analysis suggest that Ac225-PSMA therapy has higher efficacy and fewer side effects compared to beta-emitters like Lutetium-177. However, there is a potential risk of significant damage to healthy tissues if the radionuclide is not retained at the tumor site. Further research is needed to optimize its use and minimize adverse effects. ^{1 2 3 6 7}

Is the treatment Ac225-PSMA I&T a promising treatment for prostate cancer?

Yes, Ac225-PSMA I&T is a promising treatment for prostate cancer. It has shown encouraging results in patients with advanced prostate cancer, especially those who did not respond to other treatments. This treatment targets cancer cells more effectively and has fewer side effects compared to some other therapies. ^{1 2 3 5 6}

Research Team

Keith Barnett

Principal Investigator

Fusion Pharmaceuticals Inc.

Eligibility Criteria

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.

I am 18 years old or older.

Life expectancy of 6 months or more

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.

Treatment Details

Interventions

• Ac225-PSMA I&T (Radioisotope Therapy)

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.

Participant Groups

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%).

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

In vitro dose effect relationships of actinium-225- and lutetium-177-labeled PSMA-I&T. [2022]

2. Switzerland 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

First Clinical Results for PSMA-Targeted α-Therapy Using 225Ac-PSMA-I&T in Advanced-mCRPC Patients. [2021]

4. Germany 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical Experience with [225Ac]Ac-PSMA Treatment in Patients with [177Lu]Lu-PSMA-Refractory Metastatic Castration-Resistant Prostate Cancer. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Development of [225Ac]Ac-PSMA-I&T for Targeted Alpha Therapy According to GMP Guidelines for Treatment of mCRPC. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

A Review of 177Lutetium-PSMA and 225Actinium-PSMA as Emerging Theranostic Agents in Prostate Cancer. [2022]