An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With Soc, Versus SoC Alone, in Adult Male Patients With mHSPC

• Status: Recruiting
• Trial end date: 2025-12-18
• Target enrollment: 0
• Participant gender: Male

Summary

The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care, versus Standard of Care alone, in adult male patients with mHSPC. In this study, the SoC is defined as a combination of Androgen Receptor Directed Therapy + Androgen Deprivation Therapy. Approximately 1126 patients will be randomized in this study.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Collaborators: Alliance Foundation Trials, LLC.; RTOG Foundation, Inc.
• Treatments: 177Lu-PSMA-617; Gallium 68 PSMA-11

Criteria

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

1. Signed informed consent must be obtained prior to participation in the study

2. Patients must be adults ≥18 years of age

3. Patients must have an ECOG performance status of 0 to 2

4. Patients must have a life expectancy >9 months as determined by the study investigator

5. Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site)

6. Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader

7. Patients must have documented metastatic disease to bone and/or soft tissue/visceral sites documented in one of the following manners within 28 days prior randomization:

1. Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans. OR

2. Lymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis. OR

3. Visceral metastases of any size or distribution. If a subject has a history of visceral metastases at any time prior to registration, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes).

8. Patients must have adequate organ function:

• Bone marrow reserve ANC ≥1.5 x 109/L Platelets ≥100 x 109/L Hemoglobin ≥9 g/dL

• Hepatic Total bilirubin ≤2 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome ≤3 x ULN is permitted Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3.0 x ULN OR ≤5.0 x ULN for patients with liver metastases

• Renal eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation

9. Albumin ≥2.5 g/dL

10. Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial

11. Patients must be:

Treatment naïve OR minimally treated with:

• Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or bilateral orchiectomy with or without first generation anti-androgen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation anti-androgen must be discontinued prior to start of therapy.

• If received, prior LHRH agonist/antagonist use in the adjuvant/neo-adjuvant setting must have been discontinued > 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy.

• Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. No exposure for earlier stages of prostate cancer is allowed.

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for inclusion in this study.

1. Patients with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy

2. Any systemic anti-prostate cancer therapy (with the exception of the drugs listed on inclusion criteria 11), including chemotherapy, PARP inhibitors, immunotherapy or biological therapy (including monoclonal antibodies).

3. Other concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, or investigational therapy

4. Previous treatment with any of the following within 6 months of randomization:

Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted radioligand therapy is not allowed

5. Ongoing participation in any other clinical trial

6. Use of other investigational drugs within 30 days prior to day of randomization

7. Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes

8. Transfusion for the sole purpose of making a subject eligible for study inclusion

9. Patients with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast).

10. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, patients 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 patients with adequately treated non-melanoma skin cancer, superficial bladder cancer. Note: Patients with a history of CNS metastases that have received prior therapy and are neurologically stable, asymptomatic and not receiving corticosteroids are allowed.

11. Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, uncontrolled infection, known active hepatitis B or C, or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation. Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent may be included only when completely recovered (in accordance with local guidance) and had no symptoms for at least 28 days before the first dose of study medication

12. No active clinically significant cardiac disease defined as any of the following:

• NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF > 45% with improvement in symptoms to class < 3.

• History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)

• History of familial long QT syndrome or known family history of Torsades de Pointes

• Cardiac or cardiac repolarization abnormality, including any of the following:

History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature

13. History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study

14. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression

15. Any condition that precludes raised arms position

16. Concurrent bladder outflow obstruction or unmanageable urinary incontinence

17. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 6 months after stopping study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF