Personalized vs. Fixed-Activity 177Lu-PSMA-617 Radiopharmaceutical Therapy (PRODIGY-2)

Prior treatment

• Site(s) of disease that are FDG-positive, defined as SUVpeak in at least one lesion that is superior to twice (2x) SUVmean of the liver, and PSMA-negative (as above), within 45 days prior to randomization;
• Prior radiopharmaceutical therapy;
• Known CNS metastasis unless they are deemed to be non-progressive, asymptomatic and off corticosteroid therapy for at least four weeks, as per investigator's assessment;

Other illness

• Active malignancy other than prostate cancer;
• Any other condition, diagnosis or finding that may in the investigator's opinion interfere with trial conduct;
• Known hypersensitivity to 177Lu-PSMA-617 or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

Lab values

• Prior treatment with more than two lines of chemotherapy for mHSPC and/or mCRPC (adjuvant and neoadjuvant chemotherapy does not count) towards the maximum of two regimens);

Other

• PSMA-PET "superscan" (i.e. extensive/diffuse PSMA-positive bone involvement);
• Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception;

• Patient aged ≥18 years with metastatic adenocarcinoma of the prostate, defined by documented histopathology of prostate adenocarcinoma;
• Castration-resistant prostate cancer, as defined as disease progressing despite castration by orchiectomy or ongoing androgen deprivation therapy;
• Progressive mCRPC with rising PSA level, defined by PCWG3 criteria (sequence of two rising values above a baseline at a minimum of 1-week intervals, with serum testosterone level ≤ 1.7 nmol/dL);
• PSA ≥2 ng/mL ;
• Prior treatment with at least one ARPI;
• PSMA-expressing cancer, with significant PSMA expression defined as SUVpeak in at least one lesion that is superior to SUVmean of the liver on PSMA-PET (68Ga-PSMA-11 or 18F-DCFPyL), within 45 days prior to randomization;
• ECOG Performance status 0 to 2;
• Calculated eGFR (by CKD-EPI formula) ≥ 45 mL/min/1.73m\^2;
• Albumin ≥ 25 g/L;
• Platelets ≥ 100x10\^9/L;
• Neutrophils ≥ 1.5x10\^9/L;
• Hemoglobin ≥ 90 g/L without transfusion in the past 4 weeks;
• Signed, written informed consent