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

PHASE3RECRUITING

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.

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Study details:

The primary objective of the study is to compare radiographic progression-free survival (rPFS) in participants who receive 177Lu-TLX591 with SOC to rPFS in participants who receive SOC only. This study consists of three Parts:. * Part 1: Safety and Dosimetry Lead-in,.

* Part 2: Randomized Treatment Expansion, and. * Part 3: Long-term Follow-up. The study will commence with a 30-patient safety and dosimetry lead-in (Part 1) and proceed to a randomization treatment expansion in approximately 400 patients (Part 2).

Patients in Part 2 will be randomized in a 2:1 ratio to receive either 177Lu-TLX591 + Standard of Care SoC (Group A), or SoC alone (Arm B). SoC in this trial is either: ARPI (enzalutamide or abiraterone) or docetaxel. All patients will be followed in long-term follow-up for at least 5 years from the first therapeutic dose, death, or loss to follow up (Part 3).

Only patients that meet PSMA-positivity criteria per Blinded Independent Central Review (BICR) will be eligible for this study.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

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 their first ARPI (abiraterone or enzalutamide), received in either mCSPC (de novo or recurrent) or first-line mCRPC treatment setting. Participants may have received docetaxel in the mCSPC setting following the CHARTERED or STAMPEDE treatment regimens (6 cycles of docetaxel every 3 weeks) provided the last dose of therapy was ≥6 months prior to screening and ≥4 cycles 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.

Must have recovered to ≤ Grade 1 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 ≥2×109/L. Hemoglobin >10g/dL (with no red blood cell transfusion in the previous 4 weeks). Lymphocyte count >1.0x109/L. 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.

Have the capacity to understand the study and be able and willing to comply with all protocol requirements.

Participants must comply with the radiation protection rules (including hospital admissions and isolation) that are used by the treating institution in order to protect their contacts and the general public, especially if a female partner of the participant is or could be pregnant.

Must agree to practice adequate precautions to prevent pregnancy in a partner and to avoid potential problems associated with radiation exposure to the unborn child (Recommendations related to contraception and pregnancy testing in clinical trials Version 1.1, [CTFG (Clinical Trial Facilitation Group), 2020]).

Exclusion criteria

Is unable to understand or is unwilling to sign a written informed consent document or to follow investigational procedures in the opinion of the Investigator.

Has PC associated with pathological findings consistent with small cell or any histology other than adenocarcinoma of the prostate. If there are minor (<20%) elements of neuroendocrine histology, this is acceptable.

Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease-free for more than 3 years are eligible, as are participants with adequately treated non-melanoma skin cancer, and superficial bladder cancer.

Is at increased risk of hemorrhage or bleeding, or with a recent history (within the last 6 months) of a thromboembolic event (e.g., deep vein thrombosis [DVT] / pulmonary embolism [PE]) and have been administered long-term anti-coagulant or anti-platelet agents, with the exception of low dose aspirin (75 to 100 mg daily).

Has received prior treatment with monoclonal antibody (mAb) J591 or HuJ591 or any other PSMA targeted therapy.

Have received chemotherapy in the mCRPC or non-metastatic prostate cancer (nmCRPC) settings (note: prior docetaxel use in the mCSPC setting with CHAATERED or STAMPEDE regimens is permitted if the last dose of therapy was ≥6 months prior to screening and ≥4 cycles of docetaxel were administered).

Has known allergies, hypersensitivity, or intolerance to the investigational drug or its excipients.

Has received prior systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy, or biological therapy) and/or radiation therapy within 4 weeks of enrolment (excluding ARPI and/or LHRH analogues).

OR if any significant AEs have not resolved to National Cancer Institute (NCI) AE Criteria ≤ 2.

OR are receiving other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.

Has received prior treatment with radioisotopes, including but not limited to: 89Strontium, 153Samarium, 186Rhenium, 188Rhenium, 223Radium, or hemi-body irradiation within 6 months prior to enrolment.

Has received other investigational therapy within 4 weeks of enrolment.

Has known brain metastases with long-axis ≥1cm, or liver metastases with long-axis ≥1cm, or lytic bone metastases with long-axis ≥1cm.

Has a history of seizure and/or stroke within the past 6 months. Has clinical or radiologic findings indicative of impending spinal cord compression or experience symptomatic spinal cord compression.

Has evidence of a serious active or sub-clinical infection or angina pectoris (New York Heart Association [NYHA] Class III or IV), significantly prolonged QT interval or other serious illness(es) involving the cardiac, respiratory, central nervous system, renal, hepatic or hematological organ systems, that might impair the ability to complete this study or could interfere with determination of causality of any adverse effects experienced in this study, or which require treatment that could interact with study treatment, particularly with enzalutamide.

Has received treatment with any PARP inhibitors (i.e., Olaparib) or with any platinum based anti-neoplastic drugs.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: Male

Things to know

Study dates

Study start: 2024-07-26

Primary completion: 2027-12-01

Study completion finish: 2030-12-01

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT06520345

Intervention or treatment

DRUG: 177Lu-TLX591

DRUG: Enzalutamide

DRUG: Abiraterone

DRUG: Docetaxel

Conditions

• Metastatic Castration-resistant Prostate Cancer

Image related to Metastatic Castration-resistant Prostate Cancer

Condition: Metastatic Castration-resistant Prostate Cancer
DRUG: 177Lu-TLX591 and other drugs
Sydney, New South Wales, Australia and more
Sponsor: Telix Pharmaceuticals (Innovations) Pty Limited

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Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Nepean Hospital

Research sites nearby

Select from list below to view details:

Nepean Hospital
Sydney, New South Wales, Australia
Wollongong Hospital
Wollongong, New South Wales, Australia
Westmead Hospital
Sydney, New South Wales, Australia
Australian Prostate Centre
Melbourne, Victoria, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel 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 Participants randomized to Group A will receive two 76 mCi (±10%) doses of 177Lu-TLX591 14 days apart
ACTIVE_COMPARATOR: Control Arm (Enzalutamide or Abiraterone or Docetaxel) 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	DRUG: Enzalutamide Enzalutamide (starting dose 160 mg daily) + prednisone / prednisolone (5 mg twice a day) or equivalent.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 177Lu-TLX591 + Enzalutamide or Abiraterone or Docetaxel

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

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

ACTIVE_COMPARATOR: Control Arm (Enzalutamide or Abiraterone or Docetaxel)

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

DRUG: Enzalutamide

Enzalutamide (starting dose 160 mg daily) + prednisone / prednisolone (5 mg twice a day) or equivalent.

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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 outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Overall Survival	Defined as the time from randomization, until death from any cause.	5 years
Objective Response Rate (ORR)	Tumor response in terms of PCWG3 criteria (which incorporates RECIST 1.1 for soft tissue lesions).	337days
Time to a first symptomatic skeletal event (SSE)	Time to a first SSE, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-vertebral), or occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention.	337days

Frequently Asked Questions

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References

Clinical Trials Gov: The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT GLOBAL)