FPI-2265 for Metastatic Prostate Cancer

(AlphaBreak Trial)

Recruiting at 18 trial locations

Overseen By Clinical Trials Fusion Pharmaceuticals Inc.

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Fusion Pharmaceuticals Inc.

Must be taking: Androgen-deprivation therapy

Must not be taking: Cytotoxic chemotherapy

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16-32 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called FPI-2265 (also known as 225Ac-PSMA-I&T) to assess its safety and tolerability in individuals with advanced prostate cancer that has metastasized. The study targets those who have previously received lutetium-177 PSMA therapy. Participants must have a positive PSMA PET/CT scan and must have completed their prior treatment at least six weeks before joining. The trial aims to determine the optimal dose and regimen for this new drug. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that FPI-2265, a treatment for advanced prostate cancer, has promising safety results in studies with patients who have tried other treatments. Early data indicate that FPI-2265 is generally well-tolerated, even by those with extensive previous treatments. Most patients did not experience severe side effects. Some mild to moderate side effects occurred, but they were manageable. The treatment remains under study, with safety being closely monitored. This ongoing research will help determine the best dose and schedule for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for prostate cancer?

FPI-2265 is unique because it leverages a targeted approach using 225Ac-PSMA-I&T, which specifically targets prostate-specific membrane antigen (PSMA) present in metastatic prostate cancer cells. Unlike traditional treatments such as hormone therapy or chemotherapy, which can affect both cancerous and healthy cells, this targeted radioligand therapy aims to deliver radiation directly to cancer cells, potentially reducing side effects. Researchers are excited about FPI-2265 because it offers the promise of a more precise treatment that could improve outcomes for patients with tough-to-treat metastatic prostate cancer.

What evidence suggests that this trial's treatment could be effective for metastatic prostate cancer?

Research has shown that FPI-2265 (225Ac-PSMA-I&T), which participants in this trial may receive, may help treat advanced prostate cancer that no longer responds to standard hormone therapy. Early results indicate it benefits patients who have already tried many treatments, including similar ones like 177Lu-PSMA. This treatment targets a protein on prostate cancer cells and uses tiny particles to destroy them. Initial findings suggest FPI-2265 might be effective even when other treatments have failed, offering hope as a new option for those with advanced prostate cancer. ^{1 2 3 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 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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• FPI-2265 (225Ac-PSMA-I&T)

Trial Overview The 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.

How Is the Trial Designed?

Group I: Part B Arm 7 Experimental Treatment 1 Intervention

Group II: Part B Arm 6 Experimental Treatment 1 Intervention

Group III: Part B Arm 5 Experimental Treatment 1 Intervention

to be utilized based on analysis of Part A

Group IV: Part B Arm 4 Experimental Treatment 1 Intervention

to be utilized based on analysis of Part A

Group V: Part A Arm 3 Experimental Treatment 1 Intervention

Group VI: Part A Arm 2 Experimental Treatment 1 Intervention

Group VII: Part A Arm 1 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Fusion Pharmaceuticals Inc.

Lead Sponsor

Trials

6

Recruited

590+

Published Research Related to This Trial

Targeted alpha therapy using 225Ac-labeled PSMA-617 has shown remarkable therapeutic efficacy in treating metastatic castration-resistant prostate cancer, highlighting its potential as a treatment option.

The review also discusses the production methods for 225Ac and its daughter nuclide 213Bi, along with clinical experiences in using these alpha emitters for various cancers, including bladder cancer and brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Overview of Targeted Alpha Therapy with 225Actinium and 213Bismuth. Morgenstern, A., Apostolidis, C., Kratochwil, C., et al.[2019]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

The PSMA inhibitor (PSMA I&T) demonstrated strong binding affinity to prostate-specific membrane antigen (PSMA) and showed effective tumor targeting in preclinical models, indicating its potential for imaging and therapy in metastatic prostate cancer.

Initial human studies using (68)Ga-PSMA I&T for PET imaging successfully detected metastatic lesions with high contrast, and (177)Lu-PSMA I&T treatment in two patients was effective and safe, showing no detectable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies. Weineisen, M., Schottelius, M., Simecek, J., et al.[2018]

The new α-particle-emitting compound 225Ac-L1 shows specific targeting and effective cell kill in prostate cancer cells that express PSMA, demonstrating significant tumor growth inhibition and improved survival in xenograft models.

While 225Ac-L1 has promising efficacy, it also presents some off-target radiotoxicity, particularly in the kidneys and liver, with a maximum tolerated dose estimated at about 1 MBq/kg, indicating a need for careful dosing in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of 213Bi- and 225Ac-Labeled Low-Molecular-Weight Compounds for Radiopharmaceutical Therapy of Prostate Cancer. Banerjee, SR., Lisok, A., Minn, I., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Multiple Bone Metastases of Castration-Resistant Prostate Cancer With 225 Ac-PSMA-617. Yang, H., Zhang, Y., Su, D., et al.[2023]

The study of 32 patients with metastatic castration-resistant prostate cancer (mCRPC) showed that the radiolabeled antibody 225Ac-J591 is safe, with a maximum tolerated dose not reached and only one patient experiencing dose-limiting toxicity.

Preliminary efficacy results indicated that 46.9% of patients had at least a 50% decline in prostate-specific antigen (PSA) levels, and 59.1% showed a response in circulating tumor cell counts, suggesting potential effectiveness of this novel therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Tagawa, ST., Thomas, C., Sartor, AO., 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 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

225Ac-Prostate-Specific Membrane Antigen Therapy for Castration-Resistant Prostate Cancer: A Single-Center Experience. Sanli, Y., Kuyumcu, S., Simsek, DH., et al.[2023]

The study demonstrated that 99mTc-EDDA/HYNIC-iPSMA has a high tumor uptake in prostate cancer patients, with an average tumor/background ratio of 8.99, indicating its potential as an effective imaging agent for targeting prostate cancer.

The safety profile of 99mTc-EDDA/HYNIC-iPSMA was confirmed, as the absorbed radiation doses were comparable to those of other 99mTc studies, with an effective dose of 3.42 mSv, suggesting it is a safe option for imaging in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

99mTc-labeled PSMA inhibitor: Biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients. Santos-Cuevas, C., Davanzo, J., Ferro-Flores, G., et al.[2018]

The FDA has approved 177Lu-PSMA-617 for treating advanced metastatic castrate-resistant prostate cancer (mCRPC), marking a significant advancement in PSMA-targeted therapies.

Various PSMA-targeted radiopharmaceuticals, including both beta and alpha emitters, are in development, with promising results for alpha therapies like 225Ac-PSMA-617, although there are concerns about potential toxicity to salivary and renal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate specific membrane antigen binding radiopharmaceuticals: Current data and new concepts. Sartor, O., Baghian, A.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06402331

NCT06402331 | FPI-2265 (225Ac-PSMA-I&T) for Patients ... The purpose of the study is to determine the safety and tolerability, and recommended dose and regiment of FPI-2265.

2. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT224/742604/Abstract-CT224-Preliminary-efficacy-and-safety

Preliminary efficacy and safety results from the (TATCIST) trial ... Preliminary efficacy and safety data as of 30Jan24 suggest that FPI-2265 is active in heavily pretreated pts with progressive mCRPC, including pts who received ...

3. prnewswire.com prnewswire.com/news-releases/fusion-pharmaceuticals-announces-presentation-of-interim-data-from-the-phase-2-tatcist-clinical-trial-evaluating-fpi-2265-at-the-aacr-annual-meeting-2024-302112266.html

Fusion Pharmaceuticals Announces Presentation of ... Preliminary data demonstrate FPI-2265 is active in heavily pretreated patients with progressive metastatic castration-resistant prostate cancer (mCRPC).

4. onclive.com onclive.com/view/psma-directed-targeted-alpha-therapy-shows-activity-in-heavily-pretreated-metastatic-crpc

PSMA-Directed Targeted Alpha Therapy Shows Activity in ... FPI-2265 showed promising activity in patients with metastatic castration-resistant prostate cancer which was similar to prior safety and ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12388893/

Exploring the Clinical Insights into [225Ac]Ac-PSMA and Its ... Compared with [177Lu]Lu-PSMA, [225Ac]Ac-PSMA appears effective even in cases of beta-refractory disease, highlighting its complementary role ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06909825

NCT06909825 | FPI-2265 (225Ac-PSMA-I&T) and Olaparib ... The purpose of this investigation is to determine the recommended FPI-2265 dose and regimen. Conclusions from this Phase 2 study will be based on safety, ...