177Lu-PSMA-617 for Prostate Cancer

Overseen By Ethan Lam

Age: Any Age

Sex: Male

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must be taking: Chemotherapy, ARSI

Must not be taking: Myelosuppressive therapy

Disqualifiers: New prostate cancer therapy, 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: 15

Duration: 36 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a second round of the radioactive drug 177Lu-PSMA-617 (also known as Pluvicto or Lutetium Lu 177-PSMA-617) can benefit men with prostate cancer that has spread and continues to grow despite treatments to block male hormones. This drug targets cancer cells, delivering radiation to potentially kill them and improve survival chances. The trial is specifically for those who responded well to an initial round of this treatment and are experiencing a rise in PSA levels (a protein related to prostate cancer) after stopping treatment. It is suitable for those who have already tried chemotherapy and certain hormone-blocking medications and initially responded well to the 177Lu-PSMA-617 therapy. As a Phase 2 trial, this study measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to important research on improving prostate cancer therapies.

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 start new prostate cancer therapies within two months of completing the first regimen of 177Lu-PSMA-617 therapy, except for first-generation ADT, which is allowed.

Is there any evidence suggesting that 177Lu-PSMA-617 is likely to be safe for humans?

Research has shown that 177Lu-PSMA-617 has been tested for safety in treating prostate cancer. In earlier studies, many patients handled the treatment well. Common side effects included dry mouth and tiredness, but these were usually manageable. More serious side effects, such as low blood cell counts, occurred less frequently.

Another study examined long-term safety and found that serious side effects were rare. The treatment also has approval for other conditions, suggesting it is generally safe. However, patients should always consult their doctor to understand the risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about 177Lu-PSMA-617 because it offers a new approach to treating prostate cancer by directly targeting prostate-specific membrane antigen (PSMA), which is abundant on prostate cancer cells. Unlike traditional treatments such as hormone therapy or chemotherapy, which can affect the whole body, 177Lu-PSMA-617 delivers radiation directly to the cancer cells, potentially reducing damage to healthy tissues. This targeted therapy could lead to fewer side effects and more effective treatment outcomes, making it a promising option for patients.

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

Research has shown that 177Lu-PSMA-617, the treatment under study in this trial, effectively treats advanced prostate cancer that no longer responds to hormone therapy. One study found that patients receiving 177Lu-PSMA-617 with standard care lived longer without their cancer worsening, averaging 8.7 months compared to 3.4 months with standard care alone. Additionally, about half of the patients treated with this drug experienced a drop of more than 50% in their PSA levels, a protein used to monitor prostate cancer. Real-world data also supports its effectiveness, showing improved overall survival rates. This treatment delivers targeted radiation to prostate cancer cells, potentially killing them and slowing the disease. ^{1 2 5 6 7}

Who Is on the Research Team?

Jeremie Calais

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for men with prostate cancer that has spread beyond the original site and doesn't respond to hormone therapy or surgery. Participants must have had a good response to initial treatment with a radioactive drug called 177Lu-PSMA-617.

Inclusion Criteria

Platelets > 100,000 cells/µL

Patients must have the ability to understand and sign an approved informed consent form (ICF) and comply with all protocol requirements

I have completed at least 4 cycles of 177Lu-PSMA-617 therapy.

Exclusion Criteria

My kidney function is reduced with a creatinine clearance below 50 mL/min.

I haven't had certain cancer treatments or radiation therapy in the last 6 weeks.

I started a new prostate cancer treatment within two months after my first 177Lu-PSMA-617 therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 177Lu-PSMA-617 intravenously on day 1 of each cycle, with treatment repeating every 6 weeks for up to 6 cycles

36 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up visits every 3 months for up to 2 years

2 years

8 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-PSMA-617

Trial Overview The study is testing if giving patients more doses of the radioactive drug 177Lu-PSMA-617 can help improve survival and disease outcomes in those who previously responded well to this treatment. It includes scans and tests to monitor effects.

How Is the Trial Designed?

Group I: Treatment (177Lu-PSMA-617) Experimental Treatment 7 Interventions

Patients receive 177Lu-PSMA-617 IV on day 1 of each cycle. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive gallium Ga 68 gozetotide IV and undergo PET/CT at screening and on study, undergo SPECT/CT on study, and undergo collection of blood samples throughout the trial.

177Lu-PSMA-617 is already approved in United States, European Union for the following indications:

Approved in United States as Pluvicto for:

• Metastatic castration-resistant prostate cancer

Approved in European Union as Pluvicto for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

The study successfully prepared a patient dose of (177)Lu-labeled PSMA-617 with over 98% radiochemical purity, indicating a high-quality formulation for potential use in prostate cancer treatment.

Preliminary clinical investigations in 7 prostate cancer patients showed that (177)Lu-labeled PSMA-617 had a distribution pattern similar to that of diagnostic (68)Ga-PSMA-11 PET scans, suggesting its potential for theranostic applications, although further studies with larger patient groups are needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical translation of (177)Lu-labeled PSMA-617: Initial experience in prostate cancer patients. Das, T., Guleria, M., Parab, A., et al.[2021]

A reliable multidose formulation of [177Lu]Lu-PSMA-617 was developed for treating metastatic castrate-resistant prostate carcinoma (mCRPC), achieving a high radiochemical yield of 97.30% and purity of 98.24%, making it suitable for routine hospital use.

Preclinical studies showed that [177Lu]Lu-PSMA-617 specifically binds to prostate cancer cells and demonstrates significant localization in tumor regions, indicating its potential therapeutic efficacy in mCRPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Multidose Preparation of a Ready-to-Use 177Lu-PSMA-617 Using Carrier Added Lutetium-177 in a Hospital Radiopharmacy and Its Clinical Efficacy. Chakraborty, A., Mitra, A., Tawate, M., et al.[2022]

In a study of 50 men with advanced prostate cancer, 177Lu-PSMA-617 demonstrated a 64% rate of PSA decline of at least 50%, indicating its efficacy in targeting prostate-specific membrane antigen for treatment.

The treatment was associated with low toxicity, with common side effects being mild and self-limiting, and patients reported improved quality of life, with median overall survival reaching 13.3 months, particularly benefiting those who achieved significant PSA reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-up and Outcomes of Retreatment in an Expanded 50-Patient Single-Center Phase II Prospective Trial of 177Lu-PSMA-617 Theranostics in Metastatic Castration-Resistant Prostate Cancer. Violet, J., Sandhu, S., Iravani, A., et al.[2022]

[177Lu]Lu-PSMA-617 (PluvictoTM) is an FDA-approved treatment for prostate cancer specifically for patients with PSMA-positive metastatic castration-resistant prostate cancer who have already undergone other therapies.

This treatment uses a targeted radioligand therapy that delivers radiation directly to tumor cells, effectively killing them while minimizing damage to healthy tissue, as shown in multiple clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Hennrich, U., Eder, M.[2022]

The UpFrontPSMA trial is evaluating the effectiveness and safety of combining lutetium-177 (177 Lu)-PSMA-617 with docetaxel in 140 men with newly diagnosed metastatic hormone-naïve prostate cancer, aiming to determine the proportion of patients achieving undetectable PSA levels after 12 months.

This study is significant as it compares the experimental treatment to standard docetaxel therapy while all patients receive continuous androgen deprivation therapy, potentially providing insights into improved treatment strategies for this aggressive cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UpFrontPSMA: a randomized phase 2 study of sequential 177 Lu-PSMA-617 and docetaxel vs docetaxel in metastatic hormone-naïve prostate cancer (clinical trial protocol). Dhiantravan, N., Emmett, L., Joshua, AM., et al.[2021]

Treatment with lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA) significantly reduces prostate-specific antigen (PSA) levels in patients with advanced metastatic prostate cancer, especially after the first treatment cycle.

The therapy shows a beneficial effect on reducing lymph node metastasis, while also indicating potential negative impacts on visceral metastasis, highlighting its efficacy in managing certain aspects of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. Rathore, R., Rangrej, SB., Kieme, I., et al.[2023]

177Lu-PSMA-617 therapy has shown promising efficacy in treating metastatic prostate cancer, with a majority of patients experiencing a decline in prostate-specific antigen (PSA) levels, which is associated with longer survival rates.

The analysis of 17 studies indicated that while significant toxicities were infrequent, cytopenias were noted, and factors like performance status and tumor grade were important predictors of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer. Sun, M., Niaz, MO., Nelson, A., et al.[2020]

In a phase 2 trial involving 30 men with metastatic castration-resistant prostate cancer, 57% achieved a significant PSA decline of 50% or more after treatment with Lutetium-177 [177Lu]-PSMA-617, indicating its efficacy in this patient population.

The treatment was associated with low toxicity, with the most common side effects being mild dry mouth and transient nausea, and it also led to clinically meaningful improvements in pain and quality of life for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Hofman, MS., Violet, J., Hicks, RJ., et al.[2021]

[177Lu]Lu-PSMA-617 is effective in targeting prostate cancer, but some patients do not respond well; ongoing research is exploring combination therapies to improve outcomes for both treatment-naïve and resistant patients.

Combining [177Lu]Lu-PSMA-617 with other treatments, such as alpha radiation emitters and immune checkpoint inhibitors, shows promise in enhancing therapeutic responses, particularly for patients who have developed resistance to initial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. Arbuznikova, D., Eder, M., Grosu, AL., et al.[2023]

In a study involving 40 chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (mCRPC), Lutetium-177 PSMA-617 showed a best prostate-specific antigen response rate of 60%, compared to 40% for docetaxel, demonstrating its efficacy as a treatment option.

177Lu-PSMA-617 was associated with fewer severe adverse events and significantly improved quality of life compared to docetaxel, suggesting it may be a safer alternative that could be used earlier in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial. Satapathy, S., Mittal, BR., Sood, A., et al.[2022]

Citations

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

Lutetium-177–PSMA-617 for Metastatic Castration ... Lu-PSMA-617 plus standard care significantly prolonged, as compared with standard care, both imaging-based progression-free survival (median, 8.7 vs. 3.4 months ...

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

Outcomes for [ 177 Lu]Lu-PSMA-617 with and Without ... While patients on ARPIs were more likely to complete all six cycles of [177Lu]Lu-PSMA-617 (63.2% vs 48.7%, p < 0.001), PSA50 response rates were ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251559

Overall survival of prostate cancer patients treated with Lu-177 ... Median overall survival was found to be approximately 4 months higher than OS reported in VISION trial and equal to that in TheraP trial.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.97

Real world outcomes of 177 Lu-PSMA-617 ... Our results demonstrate 177 Lu-PSMA-617 effectiveness in a real-world patient population. Prospective studies are needed for further validation.

5. 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 ...

6. 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 ...

7. 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 ...