177Lu-TLX591 for Advanced Prostate Cancer

Recruiting at 14 trial locations

Overseen By Babak Saboury, MD

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called 177Lu-TLX591, a radiolabeled therapy, for men with advanced prostate cancer that has spread and no longer responds to hormone therapy. Researchers aim to determine if this treatment is safe and effective compared to existing options like Enzalutamide, Abiraterone, or Docetaxel. The trial suits men whose prostate cancer continues to grow despite low testosterone levels and who have tried other treatments without success. As a Phase 3 trial, this study represents the final step before FDA approval, offering access to a potentially groundbreaking 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that 177Lu-TLX591 is generally safe for people. Studies have found that administering the treatment in two doses, 14 days apart, is manageable for patients. This treatment combines radiation with a method targeting the immune system and has been tested in individuals with prostate cancer that exhibits a common marker called PSMA.

While most patients tolerate the treatment well, side effects may occur, as with any medical treatment. Those considering joining a trial should discuss potential risks with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about 177Lu-TLX591 for advanced prostate cancer because it offers a novel approach by using a radioactive isotope, lutetium-177, to directly target cancer cells. Unlike traditional treatments like enzalutamide, abiraterone, or docetaxel, which primarily focus on hormone pathways or chemotherapy, 177Lu-TLX591 delivers targeted radiation to the tumor, potentially minimizing damage to healthy tissues. This targeted mechanism could enhance the effectiveness of treatment and reduce side effects, making it a promising option for patients with advanced prostate cancer.

What evidence suggests that 177Lu-TLX591 might be an effective treatment for advanced prostate cancer?

Studies have shown that 177Lu-TLX591 is a promising treatment for advanced prostate cancer. In earlier trials, researchers administered this treatment safely and observed positive results in patients with a specific type of prostate cancer that has spread and does not respond to standard hormone therapy. The treatment delivers radiation directly to cancer cells, helping to shrink tumors and slow the disease. Research indicates that patients tolerated 177Lu-TLX591 well, with manageable side effects. In this trial, participants will receive either 177Lu-TLX591 combined with standard-of-care treatments (Enzalutamide, Abiraterone, or Docetaxel) or a control arm with standard-of-care treatments alone. These findings suggest that 177Lu-TLX591 could be an effective option for those who have not responded to other treatments. Larger studies are ongoing to confirm these results. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

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]

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 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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1078143924007877

4 a phase 3 study of 177lu-tlx591 plus soc vs soc alone in ... Phase 1 ProstACT SELECT preliminary results demonstrate consistent uptake between TLX591 and 68Ga-PSMA-11 imaging and reinforces advantages of this first-in- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11068829/

Lutetium-177 Labelled Anti-PSMA Monoclonal Antibody ... Lu-TLX591 was safely administered at acceptable toxicity and its efficacy reflects previous clinical trials. Larger studies are required and are underway.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS5115

ProstACT GLOBAL: A phase 3 study of best standard ... A phase 3 study of best standard of care with and without 177Lu-DOTA-rosopatamab (TLX591) for patients with PSMA expressing metastatic castration-resistant ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/64/supplement_1/P1145

177Lu-TLX591 Safety, Biodistribution and Dosimetry Study ... 177 Lu-TLX591 is a promising radioimmunotherapy candidated, with adminstered activity delivered in 2 fractions, 14 days apart demonstrating well-tolerated ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04876651

NCT04876651 | The Present Study Aims to Compare ... Participants will receive two doses of 177Lu-DOTA-TLX591(m17), 14 days apart. Screening procedures will take up to 28 days prior to enrollment and randomization ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS5109

177Lu-DOTA-TLX591 safety, biodistribution and dosimetry ... Designed to evaluate the safety, tolerability, biodistribution and dosimetry of TLX591 administered with best SoC to patients with PSMA-expressing, metastatic ...

7. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158211-asco-gu-2025-prostact-global-a-phase-3-study-of-177lu-rosopatamab-tlx591-with-and-without-the-best-standard-of-care-for-patients-with-psma-expressing-mcrpc-progressing-despite-prior-treatment-with-a-novel-androgen-axis-drug.html

A Phase 3 Study of 177Lu-Rosopatamab (TLX591) with ... Oliver Sartor discussing ProstACT GLOBAL, a phase 3 study of 177Lu-rosopatamab (TLX591) with and without the best standard of care for patients ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04786847

Study Details | NCT04786847 | 177Lu-DOTA-TLX591 ... This multi-center prospective Phase 1 study is designed to evaluate the safety, tolerability, biodistribution and dosimetry of 177Lu-DOTA-TLX591 administered to ...

9. asco.org asco.org/abstracts-presentations/ABSTRACT479654

ProstACT GLOBAL: A phase 3 study of 177Lu ... ProstACT GLOBAL: A phase 3 study of 177Lu-rosopatamab (TLX591) with and without the best standard of care for patients with PSMA expressing metastatic ...