177Lu-PSMA-617 for Prostate Cancer

Overseen By Maya Aslam

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of California, San Francisco

Must be taking: LHRH analogues

Disqualifiers: Small cell prostate cancer, Cardiovascular disease, Secondary malignancy, Active infection, others

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

Compensation: Varies

Number of Visits: 9

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of combining a targeted radiation treatment, 177Lu-PSMA-617, with liver-focused therapy for prostate cancer that has spread to the liver and resists typical hormone treatments. The trial targets patients whose prostate cancer continues to grow despite at least one advanced hormone therapy. Those battling prostate cancer with liver involvement and meeting specific criteria, such as hormone-resistant prostate cancer and liver spots visible on scans, might be suitable candidates. As a Phase 1 trial, the research focuses on understanding 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 does not specify if you need to stop taking your current medications, but you must continue LHRH analogue treatment if you haven't had a bilateral orchiectomy. Other systemic anti-cancer therapies must be stopped at least 14 days before starting the study treatment, except for LHRH analogues.

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

Research has shown that 177Lu-PSMA-617 is generally well-tolerated by patients. In studies with prostate cancer patients, this treatment has demonstrated promising safety results. For example, one study found that out of 234 participants treated with 177Lu-PSMA-617, 60.7% passed away, compared to 67.1% of those who did not receive it, suggesting a possible survival benefit.

Another study emphasized the importance of understanding long-term safety. While the treatment has been used effectively, ongoing monitoring for any side effects remains crucial. It has already been used in various settings, and many experts consider its safety profile acceptable.

In summary, while risks exist with any treatment, studies so far suggest that 177Lu-PSMA-617 is reasonably safe for prostate cancer patients. Patients should always consult their healthcare provider to understand the potential risks and benefits for their specific situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about 177Lu-PSMA-617 for prostate cancer because it targets PSMA, a molecule commonly found on prostate cancer cells, allowing for precise delivery of radiation directly to cancer sites. Unlike traditional treatments like hormone therapy or chemotherapy, which affect the entire body, 177Lu-PSMA-617 acts selectively, potentially reducing side effects and damaging fewer healthy cells. Additionally, this treatment incorporates a novel approach by combining with liver-directed therapies for patients with liver involvement, offering a tailored strategy that addresses complex cases more effectively.

What evidence suggests that 177Lu-PSMA-617 might be an effective treatment for prostate cancer?

Research has shown that 177Lu-PSMA-617, which participants in this trial may receive, is a promising treatment for advanced prostate cancer that no longer responds to hormone therapy. In several studies, more than half of the patients experienced a drop in prostate-specific antigen (PSA) levels by over 50%. This indicates that the treatment effectively combats the cancer. Additionally, many patients showed positive results on their scans, with some demonstrating complete or partial improvement. These findings suggest that 177Lu-PSMA-617 effectively targets and reduces cancer in patients with this type of prostate cancer. ^{4 6 7 8 9}

Who Is on the Research Team?

Rahul Aggarwal, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for men with advanced prostate cancer that has spread to the liver and doesn't respond to hormone therapy anymore. They should have tried at least one drug targeting male hormones but still saw their cancer grow. The study isn't open to those who can't safely receive the treatments being tested or have other serious health issues.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

Progressive disease by PCWG3 criteria at study entry

I have at least one cancer spot outside the liver that shows up on a special PET scan.

Exclusion Criteria

I have had surgery or a procedure on my bile duct.

My prostate cancer is a specific type called small cell neuroendocrine.

I haven't had cancer treatment in the last 14 days, except for LHRH analogues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 177Lu-PSMA-617 radionuclide therapy combined with liver-directed therapy for up to six cycles every 6 weeks

36 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-PSMA-617
• Liver Directed Therapy

Trial Overview The study tests a combination of a radioactive drug called 177Lu-PSMA-617, which targets prostate cancer cells, along with different methods aimed directly at liver tumors like ablation (destroying tumors with heat) and TACE (blocking blood supply to tumor while delivering chemo). It's an early-phase trial where everyone gets these treatments.

How Is the Trial Designed?

Group I: Treatment (177Lu-PSMA-617) Experimental Treatment 6 Interventions

Participants with diffusely PSMA-avid disease will receive standard doses of both 177Lu-PSMA-617 (7.4 Gigabequerel (GBq) every 6 weeks for up to 6 cycles) and transarterial chemoembolization (TACE) and/or ablation. Participants with one or more PSMA-negative liver lesions and PSMA-avid disease at all other sites will be treated with a single session of liver-directed therapy (either TACE or ablation) prior to initiation of 177Lu-PSMA-617 treatment. After cycle 2 of 177Lu-PSMA-617, participants who have extrahepatic stable disease/response but hepatic stable disease or progression per RECIST v1.1 will undergo liver-directed therapy. If clinically indicated and extrahepatic disease remains stable after cycle 3 of 177Lu-PSMA-617, participants may undergo a second course of liver-directed therapy. Participants will continue on study until progressive disease, study completion, unacceptable toxicity, or death.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2107322

Lutetium-177–PSMA-617 for Metastatic Castration ... Lutetium-177 ( 177 Lu)–PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37818966/

The real-world outcomes of Lutetium-177 PSMA-617 ... The Lu-177 PSMA-617 RLT led to a significant PSA response, with 50.6% of patients achieving a >50% decrease in PSA levels. Median overall ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.82

Survival outcomes of patients (pts) with metastatic ... Characteristics and outcomes of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with lutetium-177–PSMA-617 ( ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251923

Outcomes of [177Lu] Lu-PSMA-617 Re-Treatment in ... A favorable imaging response was observed in 10 patients (50%, 10/20), with 4 achieving a complete response and 6 achieving a partial response, ...

5. 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 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40752988/

Outcomes for [ 177 Lu]Lu-PSMA-617 with and Without ... Key findings and limitations: Among 256 patients, 106 (41.4%) received an ARPI with [177Lu]Lu-PSMA-617. Those receiving an ARPI had lower ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00852-X/fulltext

Final overall survival and safety analyses of the phase III ... At the time of the final OS analysis, 299 deaths were reported in 142/234 participants (60.7%) in the 177Lu-PSMA-617 arm and 157/234 (67.1%) in ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS294

Long-term safety outcomes of 177Lu-PSMA-617 in patients ... It is important to further characterize long-term safety outcomes in 177 Lu-PSMA-617–treated patients, with particular regard to potential treatment-related ...

9. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158427-asco-gu-2025-outcomes-for-177lu-psma-617-with-and-without-concurrent-use-of-androgen-receptor-pathway-inhibitors-in-patients-with-mcrpc.html

ASCO GU 2025: Outcomes for 177Lu-PSMA-617 with and ... Median overall survival for the overall cohort was 21.3 (95% CI 16.7 – 25.9) months and significantly longer for those receiving androgen receptor pathway ...