177Lu-PSMA-617 for Prostate Cancer

(PRODIGY-2 Trial)

Overseen By Marie-Christine Dubé, Ph.D.

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Jean-Mathieu Beauregard

Disqualifiers: Active malignancy, CNS metastasis, others

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

Compensation: Varies

Number of Visits: 6

Duration: 36 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to assess if a personalized regime of 177Lu-PSMA-617 (Lutetium Lu 177 vipivotide tetraxetan, also known as Pluvicto) is feasible and safe in a population of patients with metastatic castrate-resistant prostate cancer (mCRPC). The main questions it aims to answer are: 1. Can the administered activity (cumulative or per-cycle) be increased in a majority of participants? 2. What is the incidence of some specific adverse reactions during the treatment? Researchers will compare participants receiving a personalized regime to participants receiving the standard fixed-activity regime of 177Lu-PSMA-617 to see if the activity can be safely increased through personalization based on renal dosimetry (i.e. the measure of how much radiation is actually delivered to the kidney). Participants will receive up to 6 treatments of 177Lu-PSMA-617 every 6 weeks and be regularly evaluated with imaging and laboratory tests, as well as with questionnaires.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research shows that 177Lu-PSMA-617 is effective in treating advanced prostate cancer, with many patients experiencing a reduction in prostate-specific antigen (PSA) levels, which is a marker of cancer activity. In a trial, 66% of men with metastatic prostate cancer had a PSA response to this treatment, compared to 37% who received chemotherapy. ^{1 2 3 4 5}

Is 177Lu-PSMA-617 safe for use in humans?

177Lu-PSMA-617 has been shown to be generally safe in humans, with common side effects including dry mouth, fatigue, nausea, and diarrhea, which are usually manageable. Serious side effects are rare, and the treatment is well-tolerated at different dosage levels. ^{2 6 7 8 9}

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. ^{2 3 9 10 11}

Research Team

Jean-Mathieu Beauregard, MD

Principal Investigator

CHU de Québec-Université Laval

Eligibility Criteria

This trial is for patients with metastatic castrate-resistant prostate cancer. Participants will be considered if they can undergo up to 6 treatments every 6 weeks and are able to have their radiation delivery to the kidneys measured.

Inclusion Criteria

Signed, written informed consent

PSA ≥2 ng/mL

Calculated eGFR (by CKD-EPI formula) ≥ 45 mL/min/1.73m^2

Exclusion Criteria

I have had radiopharmaceutical therapy before.

Any other condition, diagnosis or finding that may in the investigator's opinion interfere with trial conduct

My scans show extensive cancer spread to bones.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 6 treatments of 177Lu-PSMA-617 every 6 weeks, evaluated with imaging, laboratory tests, and questionnaires

36 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term follow-up

Participants are monitored for delayed adverse events and overall survival

60 months

Treatment Details

Interventions

• 177Lu-PSMA-617

Trial Overview The study tests whether a personalized dosage of the radiopharmaceutical therapy, 177Lu-PSMA-617, based on kidney dosimetry, is more effective and safe compared to a standard fixed dose in treating prostate cancer.

Participant Groups

Group I: Personalized activity Experimental Treatment 1 Intervention

Group II: Fixed activity Active Control 1 Intervention

Who Is Running the Clinical Trial?

Jean-Mathieu Beauregard

Lead Sponsor

CHU de Quebec-Universite Laval

Collaborator

Trials

177

Recruited

110,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

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

Findings from Research

In a phase I/II trial involving 20 men with high-risk localized prostate cancer, treatment with [177Lu]Lu-PSMA-617 delivered high radiation doses to tumors with minimal side effects, indicating its safety prior to surgery.

The treatment resulted in a significant PSA decline in 45% of patients, suggesting potential efficacy in reducing tumor burden before radical prostatectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administering [177Lu]Lu-PSMA-617 Prior to Radical Prostatectomy in Men with High-risk Localised Prostate Cancer (LuTectomy): A Single-centre, Single-arm, Phase 1/2 Study. Eapen, RS., Buteau, JP., Jackson, P., et al.[2023]

[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-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 II trial, the novel radiopharmaceutical 177Lu-PSMA-617 demonstrated a significantly higher prostate-specific antigen (PSA) response in men with metastatic castration-resistant prostate cancer, with 66% of patients showing a response compared to only 37% in those treated with chemotherapy (cabazitaxel).

This suggests that 177Lu-PSMA-617 may be a more effective treatment option than traditional chemotherapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radionuclide Reduces PSA in mCRPC. [2021]

177Lu-DKFZ-PSMA-617 is a safe and promising treatment for patients with metastatic prostate cancer, with individualized dosimetry calculations showing specific absorbed doses for organs like kidneys and salivary glands.

The study involved 10 patients with a mean age of 71.4 years, highlighting significant inter-individual variations in organ dose, which underscores the importance of personalized treatment planning for effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Specific Dosimetry in Radioligand Therapy (RLT) for Metastatic Prostate Cancer Using 177Lu-DKFZ-PSMA-617. Mahmoudi, E., Pirayesh, E., Deevband, MR., 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]

In a study of 10 patients with high-volume metastatic hormone-sensitive prostate cancer, 177 Lu-PSMA-617 treatment resulted in 50% of patients achieving an undetectable PSA level, indicating effective disease control.

The treatment demonstrated a median radiographic progression-free survival of 24 months, with no severe adverse events reported, suggesting that 177 Lu-PSMA-617 is both safe and effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promising Therapeutic Activity of 177Lu-PSMA-617 in Synchronous High-Volume Metastatic Hormone-Sensitive Prostate Cancer: A Pilot Experience. Satapathy, S., Yadav, MP., Ballal, S., et al.[2023]

In a study involving 64 patients with metastatic castration-resistant prostate cancer, 177Lu-PSMA-617 was found to be safe and well-tolerated, with manageable side effects such as dry mouth, fatigue, and nausea occurring in a significant number of patients.

The treatment did not lead to serious adverse events directly related to the drug, and there were no significant changes in vital signs or kidney function, suggesting a favorable safety profile for further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312). Calais, J., Czernin, J., Thin, P., 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 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]

177Lu-PSMA-617 is a promising new treatment for patients with advanced prostate cancer, specifically targeting the prostate-specific membrane antigen (PSMA) found on cancer cells.

The therapy was also experimentally applied to a female patient with metastasized leiomyosarcoma, suggesting potential for PSMA-targeted treatment in other types of tumors beyond prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. Jüptner, M., Marx, M., Zuhayra, M., et al.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Administering [177Lu]Lu-PSMA-617 Prior to Radical Prostatectomy in Men with High-risk Localised Prostate Cancer (LuTectomy): A Single-centre, Single-arm, Phase 1/2 Study. [2023]

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

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

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

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

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

Radionuclide Reduces PSA in mCRPC. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

Patient-Specific Dosimetry in Radioligand Therapy (RLT) for Metastatic Prostate Cancer Using 177Lu-DKFZ-PSMA-617. [2022]

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

Promising Therapeutic Activity of 177Lu-PSMA-617 in Synchronous High-Volume Metastatic Hormone-Sensitive Prostate Cancer: A Pilot Experience. [2023]

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

Safety of PSMA-Targeted Molecular Radioligand Therapy with 177Lu-PSMA-617: Results from the Prospective Multicenter Phase 2 Trial RESIST-PC (NCT03042312). [2023]

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

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

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

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. [2021]