177Lu-PSMA-I&T for Prostate Cancer

Not currently recruiting at 62 trial locations

Overseen By Darcy Denner

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Curium US LLC

Must be taking: ARAT therapy

Must not be taking: Radioligand therapy, Radium-223

Disqualifiers: Chemotherapy, ECOG PS ≥ 2, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 6

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to compare the safety and effectiveness of a new treatment called 177Lu-PSMA-I&T, a targeted radioligand therapy, against standard hormone therapy options for men with advanced prostate cancer that has spread and is resistant to castration, a treatment that lowers testosterone. Participants will receive either the investigational drug or one of the standard hormone therapies (Abiraterone with Prednisone or Enzalutamide) to determine which better manages their cancer. Men whose prostate cancer continues to progress despite previous hormone treatments and who can attend regular study visits might be a good fit for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like radioligand therapy, radium-223, or investigational drugs within the last 4 weeks. It's best to discuss your specific medications with the trial team.

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

Research shows that 177Lu-PSMA-I&T is generally safe for treating prostate cancer. Studies have found this treatment to be as safe and effective as other treatments for advanced prostate cancer. For instance, one study demonstrated its effectiveness in older patients, including those over 80 years old.

Some patients experienced side effects, usually mild, though a few cases involved more serious side effects, which is important to consider. Overall, research suggests that 177Lu-PSMA-I&T is well-tolerated. However, like any treatment, weighing the benefits and potential risks is crucial. For personalized advice, consulting a healthcare professional is recommended. ^{1 2 3 4 5}

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

Researchers are excited about 177Lu-PSMA-I&T because it offers a new approach for treating prostate cancer by targeting the PSMA protein, which is often found in higher amounts on prostate cancer cells. This treatment uses a radioactive particle, lutetium-177, to deliver radiation directly to the cancer cells, potentially minimizing damage to surrounding healthy tissue. Unlike standard hormone therapies like Abiraterone with Prednisone or Enzalutamide, which focus on reducing or blocking hormones that fuel cancer growth, 177Lu-PSMA-I&T provides a more direct attack on the cancer itself. This targeted approach might lead to better outcomes for patients, especially those who have not responded well to traditional treatments.

What evidence suggests that this trial's treatments could be effective for metastatic castration-resistant prostate cancer?

Research has shown that 177Lu-PSMA-I&T, which participants in this trial may receive, can help treat advanced prostate cancer that no longer responds to hormone therapy. In earlier studies, patients using this treatment lived for an average of 13 months. Additionally, about half of the patients experienced a significant drop in their prostate-specific antigen (PSA) levels, often indicating that the cancer is responding to the treatment. The treatment was generally safe, with most patients not experiencing severe side effects. Overall, 177Lu-PSMA-I&T has shown promise in helping patients live longer and reducing cancer markers. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to hormone therapy can join. They must have tried and progressed on treatments like abiraterone or enzalutamide, but not more than one type. A positive PSMA-PET scan is needed, and they should be effectively castrated with low testosterone levels. HIV or hepatitis B/C patients may qualify if well-managed. Participants need a life expectancy of at least 6 months and agree to use contraception.

Inclusion Criteria

My cancer has worsened, shown by rising PSA levels, growth of tumors, or new bone lesions.

Life expectancy of at least 6 months

My hepatitis B or C symptoms are under control.

Exclusion Criteria

My physical functioning is somewhat limited.

I have had chemotherapy for prostate cancer that did not respond to hormone therapy, with some exceptions.

Participants who have a pregnant partner or are capable of fathering a child and who are unwilling to take precautions to prevent potential harm to the fetus or prevent pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 177Lu-PSMA-I&T or hormone therapy. Those in the investigational group receive up to 6 treatments every 6 weeks.

36 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and safety labs.

156 weeks

Pharmacokinetic and Radiation Dosimetry Sub-study

30 patients participate in a sub-study with SPECT imaging after each treatment cycle for dosimetry analysis.

36 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-PSMA-I&T
• Abiraterone with Prednisone or Enzalutamide

Trial Overview This study compares the safety and effectiveness of a new treatment called 177Lu-PSMA-I&T against standard hormone therapies (abiraterone with prednisone or enzalutamide) in men whose prostate cancer has spread despite castration. It's an open-label trial where everyone knows which treatment they're getting, and it randomly assigns participants to either group.

How Is the Trial Designed?

Group I: Investigational Drug Experimental Treatment 1 Intervention

177Lu-PSMA-I\&T

Group II: Standard Of Care Hormone Therapy Active Control 1 Intervention

Abiraterone with Prednisone or Enzalutamide

Who Is Running the Clinical Trial?

Curium US LLC

Lead Sponsor

Trials

6

Recruited

1,000+

Published Research Related to This Trial

Enzalutamide treatment significantly increases PSMA expression in prostate cancer cell lines and tumors, which could make patients with low PSMA levels eligible for PSMA-directed radioligand therapy (RLT).

In a study involving human prostate cancer cell lines and a mouse model, enzalutamide treatment led to a notable increase in PSMA levels, as confirmed by PET/CT imaging, suggesting a potential strategy to enhance the effectiveness of RLT in metastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer. Staniszewska, M., Fragoso Costa, P., Eiber, M., et al.[2021]

In a study of 133 patients with non-metastatic castration-resistant prostate cancer, abiraterone acetate (AA) plus prednisone showed comparable overall survival and cancer-specific survival to enzalutamide (Enz) over a median follow-up of 36 months.

However, patients treated with AA plus prednisone had a significantly higher risk of non-cancer-caused death compared to those treated with Enz, suggesting that while both treatments are effective, AA plus prednisone may pose additional safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world survival outcome comparing abiraterone acetate plus prednisone and enzalutamide for nonmetastatic castration-resistant prostate cancer. Tsujino, T., Tokushige, S., Komura, K., et al.[2023]

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

In men with hormone-sensitive prostate cancer, androgen blockade treatment led to a significant reduction in PSMA PET imaging signals (SUVmax) by day 9, with a 30% median decrease and a 100% PSA response rate, indicating effective early treatment response.

Conversely, in men with castrate-resistant prostate cancer, androgen blockade resulted in a 45% increase in PSMA PET imaging signals by day 9, suggesting a different response pattern that may complicate treatment planning and interpretation of imaging results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid Modulation of PSMA Expression by Androgen Deprivation: Serial 68Ga-PSMA-11 PET in Men with Hormone-Sensitive and Castrate-Resistant Prostate Cancer Commencing Androgen Blockade. Emmett, L., Yin, C., Crumbaker, M., et al.[2021]

In a study of 137 chemo-naïve patients with metastatic castration-resistant prostate cancer, Enzalutamide (EZ) showed a significantly higher PSA response rate compared to Abiraterone (AA) in the first line of treatment (95.9% vs 67%).

Both AA and EZ had comparable toxicity rates and progression-free survival (PFS) outcomes, indicating that both treatments are effective and well-tolerated options for managing mCRPC without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing lines of therapy in castration-resistant prostate cancer: real-life snapshot from a multicenter cohort. Ferriero, M., Mastroianni, R., De Nunzio, C., et al.[2021]

In a study of 26 metastatic castration-resistant prostate cancer patients treated with enzalutamide or abiraterone, changes in Prostate-Specific Membrane Antigen (PSMA) expression on PET/CT scans were strongly associated with treatment response, indicating that PSMA PET/CT can be a reliable tool for monitoring efficacy.

All patients who responded to treatment also showed a decrease in PSMA expression, while non-responders had stable or increased PSMA levels, suggesting that PSMA expression changes can effectively predict patient outcomes in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of PSMA expression changes on PET/CT before and after initiation of novel antiandrogen drugs (enzalutamide or abiraterone) in metastatic castration-resistant prostate cancer patients. Plouznikoff, N., Artigas, C., Sideris, S., et al.[2021]

The ENZA-p trial is investigating the safety and efficacy of combining lutetium-177 (177 Lu)-PSMA-617 with enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC), aiming to improve prostate-specific antigen (PSA) progression-free survival (PFS) in high-risk patients.

This phase 2 trial will enroll 160 participants and assess various outcomes, including overall survival and quality of life, while also identifying potential biomarkers to personalize treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901). Emmett, L., Subramaniam, S., Joshua, AM., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e17063

Performance of 177Lu-PSMA-I&T for RLT in mCRPC Median overall survival (OS) was 13 months (95% CI: 11.7–14.3), PSA progression-free survival (PFS) was 4.1 months (95% CI: 3.4–4.8), and ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251339

Comparative Safety and Efficacy of 177Lu-PSMA-617 and ... In this first comparative analysis of 177 Lu-PSMA-617 and 177 Lu-PSMA-I&T RLT in Taiwanese mCRPC patients, both agents demonstrated similar safety and efficacy.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37321824/

Safety and Efficacy of [ 177 Lu]-PSMA-I&T Radioligand ... Conclusion: [177Lu]-PSMA-I&T RLT in mCRPC patients at least 80 y old is safe and effective, comparable to previously published data on non-age- ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0302283824026083

A Meta-Analysis and Meta-Regression of the Efficacy ... In some studies, [177Lu]Lu-PSMA therapy has been shown to decrease the level of prostate-specific antigen (PSA) by at least 50%, with a favourable toxicity ...

5. nature.com nature.com/articles/s41391-025-01034-y

Prognostic factors of PSMA-targeted radioligand therapy in ... Prognostic Performance of RECIP 1.0 Based on [(18)F]PSMA-1007 PET in Prostate Cancer Patients Treated with [(177)Lu]Lu-PSMA I&T. J Nucl Med ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10071785/

Safety and Survival Outcomes of 177Lu-Prostate-Specific ... Median overall survival was 12.6 mo (95% CI, 8.8–16.1 mo) and 31.4 mo (95% CI, 25.7–37.6 mo) from starting 177Lu-PSMA or 223Ra, respectively. Conclusion: 177Lu- ...

7. urotoday.com urotoday.com/conference-highlights/snmmi-2023/snmmi-2023-prostate-cancer/145452-snmmi-2023-safety-and-efficacy-of-177lu-psma-i-t-radioligand-therapy-in-octogenarians-with-mcrpc-report-on-80-patients-over-age-of-80.html

SNMMI 2023: Safety and Efficacy of 177Lu-PSMA-I&T ... 177 Lu-PSMA-I&T radioligand therapy in elderly mCRPC patients ≥80 years is safe and effective, comparable to previously published data of non-age selected ...

8. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00559-5/abstract

Lutetium-177 [177Lu]Lu-PSMA-I&T plus radium-223 in ... A reduction in PSA of at least 50% was observed in 18 (55%; 95% CI 36–72) patients. Grade 3 or higher treatment-related adverse events occurred ...