177Lu-TLX591 for Advanced Prostate Cancer

Recruiting at 12 trial locations

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Telix Pharmaceuticals (Innovations) Pty Ltd

Must be taking: LHRH analogues

Must not be taking: Anti-coagulants, PARP inhibitors

Disqualifiers: Other malignancies, Brain metastases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

430 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of 177Lu-TLX591 in patients with metastatic castration-resistant prostate cancer who have progressed following treatment with Androgen Receptor Pathway Inhibitor Treatment

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you should not have received certain treatments like chemotherapy or other investigational therapies within 4 weeks of enrollment. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment 177Lu-TLX591 for advanced prostate cancer?

Research on a similar treatment, Lutetium-177-PSMA-617, shows it can reduce prostate-specific antigen (PSA) levels and metastasis in advanced prostate cancer, suggesting potential effectiveness for 177Lu-TLX591 as well. ^{1 2 3 4 5}

Is 177Lu-TLX591 safe for use in humans?

There is no specific safety data available for 177Lu-TLX591, but similar Lutetium-177 based treatments like 177Lu-PSMA-617 have been used safely in prostate cancer, with research focusing on optimizing safety and managing risks. ^{4 6 7 8 9}

What makes the drug 177Lu-TLX591 unique for treating advanced prostate cancer?

177Lu-TLX591 is a novel radioligand therapy that targets prostate-specific membrane antigen (PSMA) on prostate cancer cells, similar to other treatments like 177Lu-PSMA-617, but it uses a different monoclonal antibody (rosopatamab) to deliver the radioactive lutetium-177, potentially offering a unique approach to targeting and treating advanced prostate cancer. ^{2 4 10 11 12}

Eligibility Criteria

This trial is for men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread despite treatment. They should have had prior therapy with specific drugs, be in relatively good health (ECOG status 0-2), and have a life expectancy of at least 6 months. Men who've received certain treatments like docetaxel must meet additional time criteria since their last dose.

Inclusion Criteria

My cancer is PSMA-positive as shown by a specific scan.

My platelet count is at least 150,000 per microliter.

My cancer has spread or worsened, confirmed by scans.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Safety and Dosimetry Lead-in

Initial phase to assess safety and dosimetry in 30 patients

Not specified

Randomized Treatment Expansion

Participants are randomized to receive either 177Lu-TLX591 with SOC or SOC alone

337 days

Long-term Follow-up

All patients will be followed for at least 5 years from the first therapeutic dose, death, or loss to follow-up

5 years

Treatment Details

Interventions

• 177Lu-TLX591

Trial Overview The study tests the effectiveness and safety of a new drug, 177Lu-TLX591, combined with standard care versus standard care alone in patients whose prostate cancer has worsened after Androgen Receptor Pathway Inhibitor Treatment. Standard care includes drugs like Docetaxel, Enzalutamide, Abiraterone.

Participant Groups

Group I: 177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel Experimental Treatment 4 Interventions

Lutetium (177Lu) rosopatamab tetraxetan (177Lu-TLX591) 76 mCi (±10%) given approximately 14 days apart, plus SOC. SOC is either: Concurrent enzalutamide (starting dose 160 mg daily) + prednisone / prednisolone (5 mg twice a day) or equivalent. or Concurrent abiraterone (starting dose 1,000 mg daily) + prednisone / prednisolone (5 mg once daily for the standard formulation), methylprednisolone (4 mg twice daily for the fine particle formulation) or dexamethasone (1 mg once daily) or Sequential Docetaxel: Single agent chemotherapy will consist of docetaxel given at a recommended dose of 75mg/m2 IV every 3 weeks given in combination with oral prednisone / prednisolone (5mg twice a day) or equivalent for up to 10 cycles.

Group II: Control Arm (Enzalutamide or Abiraterone or Docetaxel) Active Control 3 Interventions

SOC is either: Enzalutamide (starting dose 160 mg daily) + prednisone / prednisolone (5 mg twice a day) or equivalent. or Abiraterone (starting dose 1,000 mg daily) + prednisone / prednisolone (5 mg once daily for the standard formulation), methylprednisolone (4 mg twice daily for the fine particle formulation) or dexamethasone (1 mg once daily) or Docetaxel: Single agent chemotherapy will consist of docetaxel given at a recommended dose of 75mg/m2 IV every 3 weeks given in combination with oral prednisone / prednisolone (5mg twice a day) or equivalent for up to 10 cycles

Who Is Running the Clinical Trial?

Telix Pharmaceuticals (Innovations) Pty Ltd

Lead Sponsor

Trials

3

Recruited

870+

Telix Pharmaceuticals (Innovations) Pty Limited

Lead Sponsor

Trials

23

Recruited

2,400+

Findings from Research

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]

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]

In a study of 52 patients undergoing Lu-177-PSMA-617 radioligand therapy for metastatic castration-resistant prostate cancer, the median overall survival was found to be 55.6 weeks, highlighting the treatment's potential efficacy.

Key predictors of overall survival included lower pre-therapeutic hemoglobin levels and higher lactate dehydrogenase (LDH) levels, as well as the presence of hepatic metastasis, indicating that these factors can help guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre- and intratherapeutic predictors of overall survival in patients with advanced metastasized castration-resistant prostate cancer receiving Lu-177-PSMA-617 radioligand therapy. Wrenger, R., Jüptner, M., Marx, M., et al.[2022]

In a phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of 177Lu-PSMA-617 to standard care significantly improved both imaging-based progression-free survival (8.7 months vs. 3.4 months) and overall survival (15.3 months vs. 11.3 months).

While 177Lu-PSMA-617 was associated with a higher incidence of grade 3 or above adverse events (52.7% vs. 38.0%), it did not negatively impact the patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. Sartor, O., de Bono, J., Chi, KN., 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]

Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) has become a promising treatment option for neuroendocrine tumors and prostate cancer, with Lutathera® and Pluvicto® being key approved therapies.

The review emphasizes the need for comprehensive safety data and optimized procedures for using 177Lu radiopharmaceuticals, aiming to improve the risk-benefit balance in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. Ladrière, T., Faudemer, J., Levigoureux, E., et al.[2023]

In a patient with metastatic castration-resistant prostate cancer (mCRPC), four cycles of radioligand therapy (RLT) using 177Lu-PSMA I&T resulted in over 97% destruction of metastatic tumors, indicating high efficacy of this treatment.

The study highlights the need for individualized dosimetry to account for variations in tumor response and suggests that measuring 177Lu-PSMA activity concentrations could improve routine dosimetry practices, while also noting that the first cycle of RLT has the most significant impact on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiomics Analysis for 177Lu-DOTAGA-(l-y)fk(Sub-KuE) Targeted Radioligand Therapy Dosimetry in Metastatic Prostate Cancer-A Model Based on Clinical Example. Kelk, E., Ruuge, P., Rohtla, K., et al.[2021]

In a study involving 49 men with metastatic castration-resistant prostate cancer, fractionated doses of Lutetium-177-labeled anti-PSMA monoclonal antibody J591 (177 Lu-J591) allowed for higher cumulative radiation doses, leading to significant decreases in prostate-specific antigen (PSA) levels and improved survival rates.

The highest dose of 45 mCi/m2 resulted in notable toxicity, including reversible grade 4 neutropenia in 35.3% of patients, but also showed promising outcomes with 87.5% of patients experiencing any PSA decrease and a median survival of 42.3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of fractionated dose lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 (177 Lu-J591) for metastatic castration-resistant prostate cancer. Tagawa, ST., Vallabhajosula, S., Christos, PJ., et al.[2020]

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]

Hyperfractionation of lutetium-177 (177 Lu)-J591 for metastatic castration-resistant prostate cancer did not show additional benefits compared to single or two-dose fractionation regimens, indicating that more frequent dosing may not enhance treatment efficacy.

In a small study of six patients, 33% experienced significant declines in prostate-specific antigen (PSA) levels, but there were also notable instances of severe side effects like grade 4 neutropenia and thrombocytopenia, highlighting the need for careful monitoring and further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of Hyperfractionated Dosing of Lutetium-177-Labeled Antiprostate-Specific Membrane Antigen Monoclonal Antibody J591 (177 Lu-J591) for Metastatic Castration-Resistant Prostate Cancer. Niaz, MJ., Batra, JS., Walsh, RD., et al.[2021]

In a study of 16 patients with high-volume metastatic prostate cancer, treatment with lutetium-177-PSMA-617 combined with LHRH analogues resulted in a 50% PSA response rate and a disease control rate of 62%, indicating its efficacy in managing the disease.

The median progression-free survival (PFS) was 11.2 months and overall survival (OS) was 29 months, with particularly favorable outcomes observed in patients with castration-resistant disease and those receiving second-line therapy, while serious side effects were limited and no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617 radioligand therapy in patients with high volume metastatic prostate cancer prior to chemotherapy and new generation androgen deprivation therapy: Clinical Experience. Celen, YZ., Elboga, U., Sahin, E., et al.[2023]

In a phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of [177Lu]Lu-PSMA-617 to standard care significantly delayed the time to first symptomatic skeletal event, with a median of 11.5 months compared to 6.8 months for standard care alone.

Patients receiving [177Lu]Lu-PSMA-617 also reported improved health-related quality of life and less pain, although there were some serious adverse events, including hematological issues, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. Fizazi, K., Herrmann, K., Krause, BJ., et al.[2023]

References

1. 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]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Pre- and intratherapeutic predictors of overall survival in patients with advanced metastasized castration-resistant prostate cancer receiving Lu-177-PSMA-617 radioligand therapy. [2022]

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

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. [2023]

5. England 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). [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Radiomics Analysis for 177Lu-DOTAGA-(l-y)fk(Sub-KuE) Targeted Radioligand Therapy Dosimetry in Metastatic Prostate Cancer-A Model Based on Clinical Example. [2021]

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

Phase 1/2 study of fractionated dose lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 (177 Lu-J591) for metastatic castration-resistant prostate cancer. [2020]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Pilot Study of Hyperfractionated Dosing of Lutetium-177-Labeled Antiprostate-Specific Membrane Antigen Monoclonal Antibody J591 (177 Lu-J591) for Metastatic Castration-Resistant Prostate Cancer. [2021]

11. Greece pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617 radioligand therapy in patients with high volume metastatic prostate cancer prior to chemotherapy and new generation androgen deprivation therapy: Clinical Experience. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. [2023]