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

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well re-treatment with 177Lu-PSMA-617 works in treating patients with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic), that continues to grow or spread after the surgical removal of the testes or medical treatment to block androgen production (castration-resistant), and that has shown a favorable response to initial treatment with 177Lu-PSMA-617. 177Lu-PSMA-617 is a radioactive drug. It binds to a protein called prostate specific membrane antigen (PSMA), which is expressed by some types of prostate tumor cells. When 177Lu-PSMA-617 binds to PSMA-expressing tumor cells, it delivers radiation to the cells, which may kill them. Re-treatment with 177Lu-PSMA-617 in patients who had a favorable response to initial 177Lu-PSMA-617 treatment may improve survival outcomes and disease response in patients with metastatic castration-resistant prostate cancer.

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.

What data supports the effectiveness of the treatment 177Lu-PSMA-617 for prostate cancer?

The treatment 177Lu-PSMA-617, also known as Pluvicto, has been shown in numerous clinical trials to effectively target and kill prostate cancer cells while sparing healthy tissue. It has been approved by the FDA for patients with advanced prostate cancer, demonstrating a positive impact on reducing prostate-specific antigen (PSA) levels and metastasis. ^{1 2 3 4 5}

Is 177Lu-PSMA-617 safe for humans?

177Lu-PSMA-617 has been shown to have low toxicity in clinical trials for prostate cancer, with common side effects including mild dry mouth and nausea. More serious side effects like low blood platelet counts and anemia occurred in a small number of patients, but no unexpected adverse events were reported. ^{1 2 4 5 6}

What makes the drug 177Lu-PSMA-617 unique for prostate cancer treatment?

177Lu-PSMA-617 is unique because it is a radiopharmaceutical that specifically targets prostate-specific membrane antigen (PSMA) on prostate cancer cells, delivering beta-minus radiation directly to the cancer cells. This targeted approach helps to minimize damage to surrounding healthy tissues, making it a promising option for patients with advanced prostate cancer. ^{1 7 8 9 10}

Research Team

Jeremie Calais

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

[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]

[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]

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]

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 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]

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-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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

Treatment of Advanced Metastatic Prostate Cancer Using Molecular-Targeted Therapy: Radioligand Lutetium-177 Prostate-Specific Membrane Antigen. [2023]

4. England 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). [2021]

5. England 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. [2021]

6. United States 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. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer. [2020]

8. Germany 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. [2022]

9. United States 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. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical translation of (177)Lu-labeled PSMA-617: Initial experience in prostate cancer patients. [2021]