Ac225-PSMA I&T for Prostate Cancer

(TATCIST Trial)

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

115 Participants Needed

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.

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.

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 data supports the effectiveness of the treatment Ac225-PSMA I&T for prostate cancer?

Research shows that Ac225-PSMA I&T, which targets prostate cancer cells, has shown promising results in reducing prostate-specific antigen (PSA) levels in patients with advanced prostate cancer, even when other treatments have failed. This suggests it may be effective in controlling the disease and improving patient outcomes. ^{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 Ac225-PSMA I&T safe for use in humans?

Clinical studies on Ac225-PSMA I&T for prostate cancer show it has promising effects with some side effects. In a study with 14 patients, no severe immediate side effects were observed, but some experienced anemia (low red blood cell count) and xerostomia (dry mouth). Overall, it appears to be generally safe, but further research is needed to fully understand its safety profile. ^{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}

How is the drug Ac225-PSMA I&T different from other prostate cancer treatments?

Ac225-PSMA I&T is unique because it uses actinium-225, an alpha emitter, which is believed to be more effective and have fewer side effects than treatments using beta emitters like lutetium-177. This drug targets prostate-specific membrane antigen (PSMA) and is particularly promising for patients with advanced prostate cancer who have not responded to 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.

Timeline

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

Treatment Details

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.

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%).

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+

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]

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]

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 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]

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]