225Ac-J591 Re-treatment for Prostate Cancer

No longer recruiting at 1 trial location

Overseen By GUONC Research Team

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: Weill Medical College of Cornell University

Must be taking: LHRH/GnRH analogues

Must not be taking: Investigational drugs

Disqualifiers: Active malignancy, DVT/PE, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a second round of the treatment 225Ac-J591 (an Alpha-PSMA-targeted radionuclide therapy) can be administered to prostate cancer patients without causing severe side effects. It focuses on men with prostate cancer that has spread and is worsening despite treatments. Participants should have previously benefited from a similar treatment without experiencing severe side effects. The trial includes two groups: one for those with moderate past exposure to similar treatments and another for those with heavy past exposure. Those who have undergone previous hormone or chemotherapy treatments and continue to experience cancer progression might be suitable candidates. As an Early Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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 must continue primary androgen deprivation therapy if you haven't had an orchiectomy (surgical removal of the testicles).

Is there any evidence suggesting that 225Ac-J591 is likely to be safe for humans?

Research has shown that 225Ac-J591, a treatment targeting prostate cancer, has been studied for safety and effectiveness. In earlier studies, patients responded to this treatment even after trying similar treatments like 177Lu-PSMA.

Researchers have tested the treatment to determine the optimal dose patients can tolerate. Common side effects have been noted, but detailed information on serious adverse reactions was not highlighted in the sources.

As this treatment is in an early phase trial, it remains in the initial stages of research. This phase aims to assess the treatment's safety. While promising, further research is necessary to fully understand its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about 225Ac-J591 for prostate cancer because it uses a novel approach by targeting prostate-specific membrane antigen (PSMA) with a radioactive payload. Unlike traditional treatments such as hormone therapy or chemotherapy, which can affect both cancerous and healthy cells, 225Ac-J591 delivers targeted radiation directly to cancer cells. This precision aims to minimize damage to healthy tissue and potentially reduce side effects. Additionally, by focusing on PSMA, this treatment may offer a new option for patients who have already undergone extensive therapies without success.

What evidence suggests that 225Ac-J591 might be an effective treatment for prostate cancer?

Research has shown that 225Ac-J591 effectively treats prostate cancer, even in patients who have previously tried 177Lu-PSMA. Studies have found that it helps manage the cancer by lowering PSA levels, which indicate prostate cancer activity. Participants in this trial will be divided into two groups: those moderately exposed and those heavily exposed to prior treatments. Specifically, patients in earlier studies experienced benefits such as longer periods without cancer progression and improved survival rates. The treatment typically causes mild side effects, making it a promising option for some prostate cancer patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Scott Tagawa, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that has spread and is resistant to hormone therapy can join. They must have had certain treatments like enzalutamide, abiraterone, or taxane chemotherapy. Good blood counts and organ function are required, and they should be able to perform daily activities with ease to moderate difficulty.

Inclusion Criteria

My prostate cancer was confirmed by a lab test.

I have had taxane chemotherapy, been told I can't have it, or refused it.

My prostate cancer is worsening, shown by rising PSA levels or new cancer spots on scans.

Exclusion Criteria

I had a blood clot in my leg or lung within the last month.

I have not had radiation therapy in the last 4 weeks.

I have been diagnosed with myelodysplastic syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of 225Ac-J591, with potential for a second dose upon progression and tolerance

12 weeks

1 visit (in-person) for each dose

Follow-up

Participants are monitored for safety and effectiveness after treatment, including short-term and long-term follow-up

100 months

Regular visits (in-person) and contact (telephone)

What Are the Treatments Tested in This Trial?

Interventions

• 225Ac-J591

Trial Overview The trial tests if a second round of the drug 225Ac-J591 for metastatic castration-resistant prostate cancer (mCRPC) can be given safely without causing severe side effects. Participants will have already seen some benefit from this type of treatment before without major toxicities.

How Is the Trial Designed?

Group I: Moderately Exposed Experimental Treatment 1 Intervention

Group II: Heavily Exposed Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

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]

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]

In a first-in-human trial, two patients with advanced prostate cancer showed a complete response to treatment with 225Ac-PSMA-617, indicating its potential efficacy as a targeted therapy.

The treatment resulted in a significant decline in prostate-specific antigen levels without relevant hematologic toxicity, suggesting a favorable safety profile, with xerostomia being the only notable side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer. Kratochwil, C., Bruchertseifer, F., Giesel, FL., et al.[2022]

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]

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]

Citations

1. urotoday.com urotoday.com/conference-highlights/aua-2025/aua-2025-prostate-cancer/160028-aua-2025-225ac-j591-psma-targeted-radionuclide-therapy-in-metastatic-castration-resistant-prostate-cancer-patients-with-prior-177lu-psma-therapy.html

AUA 2025: 225Ac-J591 PSMA-Targeted Radionuclide ... 225Ac-J591 shows efficacy in mCRPC patients following prior 177Lu-PSMA therapy; This sequential therapy is associated mostly with low-grade ...

2. auajournals.org auajournals.org/doi/10.1097/01.JU.0001109880.25183.6b.06

PD13-06 225Ac-J591 PSMA-TARGETED RADIONUCLIDE ... CONCLUSIONS: PSMA-targeted alpha radionuclide therapy using 225Ac-J591 has efficacy in patients with mCRPC despite prior 177Lu-PSMA. Common ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.185

Mature phase 1 follow up of alpha emitter 225Ac-J591 with ... Preliminary efficacy outcomes examined were overall survival (OS), progression-free survival (PFS), PSA response, and circulating tumor cell ( ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37922438/

A Phase I Dose-Escalation Study of 225Ac-J591 - PubMed - NIH This dose-escalation study investigated the safety, efficacy, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) for 225Ac-J591, ...

5. urotoday.com urotoday.com/conference-highlights/aua-2025/aua-2025-prostate-cancer/160076-aua-2025-psma-targeted-actinium-225-therapy-in-metastatic-castration-resistant-prostate-cancer-comparative-outcomes-between-monotherapy-vs-combination-therapy.html

AUA 2025: PSMA-Targeted Actinium-225 Therapy in ... Ac-J591 combination therapy demonstrated a higher PSA50 response rate compared to monotherapy (57% versus 48%), albeit not statistically ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.23.00573

A Phase I Dose-Escalation Study of 225Ac-J591 This dose-escalation study investigated the safety, efficacy, maximum tolerated dose (MTD), and recommended phase II dose (RP2D) for 225Ac-J591, ...