177Lu-PSMA-617 for Prostate Cancer

Recruiting at 2 trial locations

Overseen By Akshata Mathur

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Washington

Must be taking: Androgen deprivation therapy

Must not be taking: Radioligand therapy

Disqualifiers: CNS metastases, Congestive heart failure, 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: 19

Duration: Up to 36 weeks

51 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called 177Lu-PSMA-617, which targets prostate cancer that has spread and hasn't responded to other treatments. The treatment uses a radioactive substance to attach to cancer cells and damage their DNA, aiming to improve outcomes for patients with this type of prostate cancer. It may benefit those with metastatic castrate-resistant prostate cancer (mCRPC) who have already tried hormone therapy and chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 have any systemic anti-cancer therapy or investigational agents within 30 days before starting the trial. It's best to discuss your specific medications with the trial team.

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

In earlier studies, 177Lu-PSMA-617 has shown promising safety results for treating prostate cancer. Research indicates that patients generally tolerate it well, with few serious side effects. The VISION study found that patients who received 177Lu-PSMA-617 lived longer and maintained an acceptable safety profile, even after trying many other treatments.

Another study demonstrated that 177Lu-PSMA-617 had a better safety profile compared to other treatments. Fewer patients experienced severe side effects with 177Lu-PSMA-617 than with some other prostate cancer treatments. These findings suggest that 177Lu-PSMA-617 may be a safe option for patients with advanced prostate cancer that does not respond to other treatments. ^{1 2 3 4 5}

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

Researchers are excited about Lutetium Lu 177-PSMA-617 for prostate cancer because it targets cancer cells in a novel way. Unlike conventional treatments like hormone therapy or chemotherapy, which broadly affect the body, Lutetium Lu 177-PSMA-617 is a radioligand therapy that specifically targets the PSMA protein found on prostate cancer cells. This precision allows for direct delivery of radiation to cancer cells, potentially reducing damage to healthy tissue and improving outcomes. Additionally, the treatment's unique mechanism could offer new hope for patients who have not responded to existing therapies.

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 will receive, holds promise for treating advanced prostate cancer that no longer responds to hormone therapy. Studies found that about 50.6% of patients experienced a significant drop in prostate-specific antigen (PSA) levels, with reductions of over 50%. This often indicates effective cancer treatment. The treatment also links to longer survival times, with patients living a median of 12 months. Additionally, it generally causes mild side effects, indicating low toxicity. Overall, evidence supports 177Lu-PSMA-617 as an effective option for patients with this type of prostate cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Amir Iravani, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with prostate cancer that has spread and is resistant to treatment. Participants must have a specific low level of PSMA expression, which will be determined by scans.

Inclusion Criteria

I understand and can follow all study requirements.

My PET/CT scan shows cancer that is PSMA positive without any PSMA negative spots.

White blood cell (WBC) count ≥ 2.5 x 10^9/L

Exclusion Criteria

Known hypersensitivity to the components of the study therapy or its analogs

I have had brain metastases, received treatment, and am now stable.

I am not currently receiving any other cancer treatments like chemotherapy or immunotherapy.

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 over 30 minutes on specified days, with imaging and blood sample collection throughout the study

Up to 36 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments every 12 weeks

Up to 2 years

Every 12 weeks (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium Lu 177-PSMA-617

Trial Overview The study tests the effectiveness of an intensified dose of 177Lu-PSMA-617 in treating metastatic castrate-resistant prostate cancer (mCRPC). It involves various imaging techniques like bone scans, CTs, PET-CTs, SPECT, MRI, and biospecimen collection.

How Is the Trial Designed?

Group I: Treatment (177Lu-PSMA-617) Experimental Treatment 8 Interventions

Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Society of Nuclear Medicine and Molecular Imaging (SNMMI) Mars Shot Research Fund

Collaborator

Trials

1

Recruited

50+

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

Published Research Related to This Trial

[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]

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]

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]

In a study of 75 patients with metastatic prostate cancer, 6 were excluded from Lutetium-177 [177Lu]-PSMA-617 treatment due to PSMA-negative/FDG-positive discordance, but 89 suitable targets for biology-guided radiotherapy (BgRT) were identified.

The research suggests that combining BgRT with Lutetium-177 [177Lu]-PSMA-617 is feasible for treating patients with discordant metastases, particularly highlighting that bone and lung metastases are the most suitable candidates for this combined therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. Gaudreault, M., Chang, D., Hardcastle, N., et al.[2023]

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]

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]

In a study involving 145 patients with metastatic castration-resistant prostate cancer (mCRPC), treatment with 177Lu-PSMA-617 showed a biochemical response rate of 45%, indicating high efficacy, especially with 40% of patients responding after just one treatment cycle.

The therapy demonstrated a favorable safety profile, with only 10% of patients experiencing severe hematotoxicity and 8% reporting dry mouth, suggesting it may be a safer option compared to other third-line treatments for mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. Rahbar, K., Ahmadzadehfar, H., Kratochwil, C., et al.[2022]

A 76-year-old man with advanced prostate cancer showed significant improvement after treatment with lutetium 177 PSMA-617, indicating its potential efficacy in patients resistant to standard therapies.

The treatment led to marked biochemical and imaging responses, as well as improvements in clinical status and pain relief, highlighting the therapeutic benefits of PSMA-targeted nuclear medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-Prostate-specific Membrane Antigen Radioligand Therapy in Patients with Metastatic Castration-resistant Prostate Cancer. Parihar, AS., Hofman, MS., Iravani, A.[2023]

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 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]

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]

Citations

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

Lutetium-177–PSMA-617 for Metastatic Castration ... This radioligand therapy has been associated with encouraging biochemical and radiographic response rates, reduced pain, and low toxicity in multiple early- ...

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 ... For pts treated with Lu, the median TTNT was 8.5 months (95% CI, 7.3 – 9.8), and the median OS was 12 months (95% CI, 11 – 15). Median TTNT and ...

4. 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.

5. sciencedirect.com sciencedirect.com/science/article/pii/S258893112300161X

Real-world Outcomes and Predictive Biomarkers for 177 ... We found that 177Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy ...

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

Safety and Survival Outcomes of 177Lu-Prostate-Specific ... The VISION study investigated a β-emitter, 177Lu-PSMA-617, targeting PSMA-expressing cells and found prolonged overall survival and acceptable safety in heavily ...

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

Final overall survival and safety analyses of the phase III ... Lu-PSMA-617 had a favourable safety profile, with a lower incidence of grade 3-5 adverse events (AEs) compared with ARPI change, and no new ...