Phase 3 ProstACT™ Global: A Study of 177Lu-TLX591 + Standard of Care vs. Standard of Care Alone in PSMA Positive mCRPC – Clinical Trial Overview
Patient Summary
Purpose of This Study
The Phase 3 ProstACT™ Global study is investigating whether adults treated after only 1 androgen-receptor pathway inhibitor (ARPI) with TLX591 in combination with today’s best treatments (standard of care, SOC) can delay the progression of metastatic castration-resistant prostate cancer (mCRPC) and extend overall survival.
Doctors hope TLX591 will provide a new treatment option for men whose cancer has progressed after hormone therapy.
What Is TLX591?
TLX591 (lutetium177 rosopatamab tetraxetan) is a radio-labeled antibody therapeutic agent comprised of two key components:
- Lutetium‑177– a radionuclide that emits DNA-breaking radiation
- Rosopatamab– a PSMA-targeting (prostate-specific membrane antigen) antibody
TLX591 is administered via 2 intravenous doses given 14 days apart.
TLX591 targets PSMA, a biomarker overexpressed in more than 80% of men with prostate cancer.
TLX591 binds to PSMA, a protein expressed in prostate cancer cells. After binding to PSMA, TLX591 is internalized into the cell and emits DNA-breaking radiation, which can lead to cell death, while sparing healthy tissue from damage.
TLX591 targets PSMA+ prostate cancer cells regardless of where they have metastasized (bone, nodal, or visceral).
Why Consider Joining?
- Your prostate cancer has progressed after treatment with 1 ARPI.
- In either metastatic hormone-sensitive, non-metastatic castration resistant, or 1st line metastatic castration resistant prostate cancer treatment settings.
- Your healthcare provider recommends this trial where you may receive TLX591 in combination with standard of care (SOC), which could help slow or stop cancer growth.
- Your treatment will include advanced imaging (including gallium 68 PSMA PET/CT) and close long-term medical monitoring.
- Your participation may help improve future prostate cancer treatments.
How the Study Works
- Part 1 – Safety run in: A small group of 30 patients receive TLX591 + SoC to confirm safety before global expansion (now fully enrolled)
- Part 2 – Main study: Approximately 490 participants will be randomly divided (2:1) into two groups:
- Group A: Patients treated with TLX591 plus SOC (a change in ARPI abiraterone or enzalutamide; or docetaxel); TLX591 is administered via 2 intravenous doses given 14 days apart.
- Group B: Patients to receive SOC (a change in ARPI abiraterone or enzalutamide; or docetaxel)
- Primary endpoint: Radiographic progression-free survival (rPFS) – time until scans show progressive disease
- Secondary endpoint: Overall survival (OS) refers to the average length of time that patients with a specific disease live after their diagnosis and start of treatment.
- Follow-Up: Clinic visits, lab tests, and imaging every 6-8 weeks; long-term follow-up ≥ 5 years
Who Can Join?
You MAY qualify if you:
- Are ≥ 18 years old with metastatic prostate adenocarcinoma that is castration resistant.
- Have PSMA-positive disease based on a PSMA-PET scan
- Have received ≥ 12 weeks of therapy on 1 ARPI (abiraterone, apalutamide, darolutamide, or enzalutamide.
- Have an ECOG performance status of 0-2 and a life expectancy ≥ 6 months.
You CANNOT join if you:
- Have already received a PSMA-targeted therapy, such as Pluvicto (177Lu-PSMA-617) or prior J591 therapy.
- Underwent systemic chemo, immunotherapy, or external beam radiation within 4 weeks of enrollment.
- Have uncontrolled pain, serious bleeding risk, active brain or liver metastases, or other significant illnesses (see full list).
(This is a summary; final eligibility will be confirmed by the study team.)
What to Expect
- Patient consent
- Screening (up to 28 days): laboratory tests and PET/CT scan imaging
- Treatment phase (≈ 2 weeks): two TLX591 infusions given 14 days apart for Group A plus SoC; Group B receives SoC only.
- Long-term follow-up: regular visits and scans for at least five years.
Benefits & Risks
Your healthcare provider will explain important safety information to you based on the risk of radiation exposure.
Potential benefits: TLX591 may provide more time without cancer worsening and may shrink tumors or make tumors disappear compared to SOC alone. High quality imaging will be included throughout the study. Previous clinical studies have demonstrated that TLX591 does not cause renal toxicity, dry mouth, or dry eye.
Potential risks: TLX591 can cause myelosuppression including decreased hemoglobin, decreased leukocyctes, decreased neutrophils, and decreased platelets. All participants receive thorough monitoring including complete blood counts before and during treatment with TLX591. TLX591 is cleared through the liver. All participants will receive thorough monitoring of hepatic laboratory values.
Standard of care treatments have their usual side effects.
TLX591 may not work for everyone.
Learn More
- ClinicalTrials.gov ID: NCT065250345
- Sponsor: Telix Pharmaceuticals (Innovations) Pty Ltd
- Discuss with your oncologist or visit ClinicalTrials.gov for site contacts.
Organization:
For additional information, visit telixpharma.com
ClinicalTrials.gov Information:
- NCT Number: NCT06520345
- Title: The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT Global)
Use the “clinical trials glossary” and “dictionary” for words, phrases and treatments that you may not understand.
Register your interest or comments about this trial with PHEN
Please Note: This information is provided for educational and awareness purposes. A decision on clinical trials participation is to be made between the patient and his doctor.
Glossary of Terms:
- PSMA: Prostate-specific membrane antigen which is a protein expressed on prostate cancer cells.
- PSMA RNT: PSMA radionuclide therapy is a targeted radiopharmaceutical treatment for prostate cancer.
- ARPI: Androgen receptor pathway inhibitor is a type of drug, primarily used to treat prostate cancer, that works by blocking the effects of male hormones like testosterone.
- mCRPC: Metastatic castration-resistant prostate cancer is cancer that has spread outside the prostate and no longer responds to hormone treatment that lowers testosterone.
- mCSPC: Metastatic castration-sensitive prostate cancer is cancer that has spread outside of the prostate and responds to hormone therapy.
- nmCRPC: Non-metastatic castration resistant prostate cancer is cancer that has not spread outside of the prostate and no longer responds to hormone treatment that lowers testosterone.
- TLX591: An investigational PSMA radionuclide therapy (RNT) for the treatment of metastatic prostate cancer following treatment with 1 ARPI.
- SoC (Standard of Care): Best accepted treatment: enzalutamide, abiraterone + prednisone, or docetaxel.
- rPFS: Radiographic progression-free survival, which is the time until imaging shows the cancer has grown or the patient dies.
- IV Infusion: Medicine delivered through a vein.
- ECOG 0 2: Activity scale: 0 = fully active, 2 = ambulatory but unable to work.
- Randomized: Patients are assigned to study groups by chance instead of by choice.
