The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT Global)

NCT06520345 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 177Lu-TLX591-203
• Study Type: interventional
• Target: 520
• Locations: 6 countries
• Sites: 31

Brief Summary

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

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Radiographic Progression Free Survival; Overall Survival; ARPI; Docetaxel; Prostate Cancer; Radionuclide therapy; TLX591; ProstACT Global; PSMA- targeting agent; mCRPC; 177Lu-TLX591; mCSPC; nmCRPC; rosopatamab tetraxetan; Lutetium; 177-Lutetium; Objective Response Rate (ORR); PSA; 68Gallium-PSMA-PET; Radio-Labelled Antibody Drug Conjugate (rADC)

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression-free Survival

  time from randomization to disease progression confirmed by central independent radiology review according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria (which incorporates Response Evaluation Criteria in Solid Tumors, RECIST 1.1, for soft tissue lesions), or death (whichever occurs first)

  337days

Secondary Outcomes (3)

• Overall Survival

  5 years

• Objective Response Rate (ORR)

  337days

• Time to a first symptomatic skeletal event (SSE)

  337days

Study Arms (2)

177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel

EXPERIMENTAL

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.

Drug: 177Lu-TLX591; Drug: Enzalutamide; Drug: Abiraterone; Drug: Docetaxel

Control Arm (Enzalutamide or Abiraterone or Docetaxel)

ACTIVE COMPARATOR

SOC is either: Enzalutamide (starting dose 160 mg daily). or Abiraterone (starting dose 1,000 mg daily) + prednisone / prednisolone (up to 10 mg once daily for the standard formulation) 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

Drug: Enzalutamide; Drug: Abiraterone; Drug: Docetaxel

Interventions

177Lu-TLX591 DRUG

Participants randomized to Group A will receive two 76 mCi (±10%) doses of 177Lu-TLX591 14 days apart

Also known as: Lutetium (177Lu) rosopatamab tetraxetan

177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel

Enzalutamide DRUG

Enzalutamide (starting dose 160 mg daily)

177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel; Control Arm (Enzalutamide or Abiraterone or Docetaxel)

Abiraterone DRUG

Abiraterone (starting dose 1,000 mg daily) + prednisone / prednisolone (up to 10 mg per day for the standard formulation)

177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel; Control Arm (Enzalutamide or Abiraterone or Docetaxel)

Docetaxel DRUG

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

177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel; Control Arm (Enzalutamide or Abiraterone or Docetaxel)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be a male, at least 18 years old, with documented adenocarcinoma of the prostate defined by histological / pathological confirmation.
• Be of ECOG Performance Status 0, 1, or 2 and have an estimated life expectancy of ≥6 months from Day 1.
• Have metastatic disease (defined as ≥1 metastatic lesion present on baseline CT, MRI or bone scintigraphy).
• Have castration-resistant PC (defined as disease progressing despite castration by orchiectomy or ongoing use of luteinizing hormone-releasing hormone \[LHRH\] analogues) and must have a castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L) at Screening
• Must have received a minimum of 12 weeks of prior therapy on an ARPI (abiraterone, apalutamide, darolutamide, or enzalutamide), received in either the mCSPC, nmCRPC, or mCRPC treatment settings, with documented evidence of disease progression while receiving this ARPI. Progression must have occurred on the most recent ARPI. A prior ARPI may have been utilized, but no progression on the prior ARPI is allowed (e,g, ARPI was switched due to poor tolerability or due to adverse events). No washout period is required prior to enrollment into this trial. Participants may have received docetaxel in the mCSPC setting as per the CHAARTED or STAMPEDE treatment regimens (up to 6 cycles of docetaxel), provided the last dose of docetaxel was ≥ 6 months prior to screening and ≥ 4 cycles of docetaxel were administered.
• Have a disease that is progressing at study entry, despite a castrate testosterone level (\<50 ng/dL or \<1.7 nmol/L), by the demonstration of at least one of the following:
• Two consecutive rising PSA values assessed sequentially at least one week apart, with the final measurement required to be a minimum of 2.0 ng/mL for study entry. Only the last measurement must meet or exceed 2.0 ng/mL.
• Progressive disease or new lesion(s) in the viscera or lymph nodes as per RECIST1.1 or in bone as per PCWG3. Any ambiguous results are to be confirmed by other imaging modalities (e.g., CT or MRI scan).
• Have disease that is PSMA-positive, as demonstrated by a 68Ga-PSMA-11 PET/CT or PET/MRI scan and confirmed as eligible by the Sponsor's appointed BICR.
• Imaging-based eligibility review will be performed in two stages:

You may not qualify if:

• PSMA positivity is defined as : At least 1 lesion with PSMA TLR≥2.
• i) visceral metastatic lesions that are ≥1 cm that have a PSMA TLR\< 1 ii) Lytic bone metastatic lesions with a soft tissue component of at least 1 cm with a TLF \<1.
• iii) At least one metastatic lymph node lesion with short axis ≥2.5 cm with a TLF\<1.
• Must have recovered to ≤ Grade 2 from all clinically significant toxicities related to prior therapies (i.e., surgery, local radiotherapy, ARPI, chemotherapy, etc.) with the exception of alopecia. Specific conditions may be discussed with the medical monitor as needed.
• Have adequate organ function at Screening:
• Bone marrow:
• Platelets ≥150×109/L.
• Absolute neutrophil count ≥1.5 x 109/L.
• Hemoglobin \>10g/dL (with no red blood cell transfusion in the previous 4 weeks).
• Liver function:
• Total bilirubin ≤ 1.5× the upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤3× ULN is permitted.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3× ULN.
• Renal function:
• Creatinine clearance ≥45 mL/min determined using the Cockcroft-Gault formula.
• Must understand the study and agree to adhere to all protocol requirements.

Sponsors & Collaborators

• Telix Pharmaceuticals (Innovations) Pty Limited: lead

Study Sites (31)

Chao Family Comprehensive Cancer Centre

Orange, California, 92868, United States

ACTIVE NOT RECRUITING

Biogenix Molecular LLC

Miami, Florida, 33165, United States

ACTIVE NOT RECRUITING

United Theranostics

Glen Burnie, Maryland, 21061, United States

ACTIVE NOT RECRUITING

XCancer Omaha

Omaha, Nebraska, 68130, United States

ACTIVE NOT RECRUITING

Columbia University Herbert Irving Comphrensive Cancer Center

New York, New York, 10032, United States

RECRUITING

University Hospital

Cleveland, Ohio, 44106, United States

ACTIVE NOT RECRUITING

OHSU Knight Cancer Center

Portland, Oregon, 97239, United States

ACTIVE NOT RECRUITING

Intermountain Health

Murray, Utah, 84107, United States

ACTIVE NOT RECRUITING

Intermountain Health

Salt Lake City, Utah, 84112, United States

ACTIVE NOT RECRUITING

Westmead Hospital

Sydney, New South Wales, 2143, Australia

RECRUITING

Nepean Hospital

Sydney, New South Wales, 2747, Australia

RECRUITING

Wollongong Hospital

Wollongong, New South Wales, 2500, Australia

RECRUITING

Australian Prostate Centre

Melbourne, Victoria, 3051, Australia

RECRUITING

GenesisCare Murdoch

Perth, Western Australia, 6150, Australia

RECRUITING

Mater Health Services Pty Ltd

Brisbane, 4101, Australia

NOT YET RECRUITING

GenesisCare Maitland

East Maitland, 2323, Australia

RECRUITING

Austin Health

Heidelberg, 3084, Australia

RECRUITING

GensisCare Cabrini

Malvern, 3144, Australia

RECRUITING

GenesisCare North Adelaide

North Adelaide, 5006, Australia

RECRUITING

Royal North Shore Hospital

Saint Leonards, 2065, Australia

RECRUITING

GenesisCare Tugun

Tugun, 4224, Australia

RECRUITING

INITIO Medical Group

Burnaby, Canada

RECRUITING

Sunnybrook Research Institute

Toronto, Canada

RECRUITING

Auckland City Hospital

Grafton, Auckland, 92024, New Zealand

RECRUITING

New Zealand Clinical Research - Christchurch

Christchurch, 8011, New Zealand

RECRUITING

Ankara Bilkent City Hospital

Ankara, Turkey (Türkiye)

NOT YET RECRUITING

Ankara University Cebeci Hospital

Ankara, Turkey (Türkiye)

RECRUITING

Hacettepe University Medical Faculty

Ankara, Turkey (Türkiye)

RECRUITING

Maslak Acibadem Hospital

Istanbul, Turkey (Türkiye)

NOT YET RECRUITING

University College London Hospitals

London, United Kingdom

RECRUITING

Genesis Care Windsor

Windsor, United Kingdom

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Lutetium; Lutetium-177; enzalutamide; abiraterone; Docetaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Lanthanoid Series Elements; Metals, Rare Earth; Elements; Inorganic Chemicals; Transition Elements; Metals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a multinational, multicenter, prospective, randomized, controlled, open-label Phase 3 study designed to investigate and confirm the benefits and risks associated with 177Lu-TLX591 administered together with SOC compared to SOC alone, in participants with PSMA-positive metastatic castration resistant prostate cancer (mCRPC) who have progressed after their first treatment with an ARPI (specifically abiraterone, apalutamide, darolutamide or enzalutamide) or docetaxel administered during either the metastatic castrate-sensitive prostate cancer (mCSPC), non-metastatic castration resistant prostate cancer (nmCRPC) or first-line metastatic castrate-resistant prostate cancer (mCRPC) treatment setting.

Study Record Dates

• First Submitted: July 12, 2024
• First Posted: July 25, 2024
• Study Start: July 26, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 27, 2026

Record last verified: 2026-05

Locations

US (9); GB (2); NZ (2); TU (4); AU (12); CA (2)