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

Launched by JEAN-MATHIEU BEAUREGARD · Apr 22, 2025

Keywords

ClinConnect Summary

The PRODIGY-2 clinical trial is exploring whether a personalized treatment approach using a radiopharmaceutical called 177Lu-PSMA-617 (also known as Pluvicto) is safe and effective for men with metastatic castrate-resistant prostate cancer (mCRPC). This trial aims to find out if adjusting the amount of treatment each patient receives can help most participants while also monitoring any side effects they might experience. Participants will receive up to six treatments, spaced six weeks apart, and will be closely monitored with imaging tests, lab work, and questionnaires throughout the study.

To participate in this trial, men must be at least 18 years old and diagnosed with prostate cancer that has spread and is not responding to standard hormone therapies. Other eligibility criteria include having specific levels of prostate-specific antigen (PSA) in their blood and a particular type of cancer that shows a certain marker on imaging tests. It’s important to note that the trial is not yet recruiting participants, but it represents an exciting opportunity for eligible patients to potentially benefit from a tailored treatment strategy.

Gender

MALE

Eligibility criteria

• Inclusion Criteria:
• • 1. Patient aged ≥18 years with metastatic adenocarcinoma of the prostate, defined by documented histopathology of prostate adenocarcinoma;
• • 2. Castration-resistant prostate cancer, as defined as disease progressing despite castration by orchiectomy or ongoing androgen deprivation therapy;
• • 3. 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);
• • 4. PSA ≥2 ng/mL ;
• • 5. Prior treatment with at least one ARPI;
• • 6. 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;
• • 7. ECOG Performance status 0 to 2;
• • 8. Calculated eGFR (by CKD-EPI formula) ≥ 45 mL/min/1.73m\^2;
• • 9. Albumin ≥ 25 g/L;
• • 10. Platelets ≥ 100x10\^9/L;
• • 11. Neutrophils ≥ 1.5x10\^9/L;
• • 12. Hemoglobin ≥ 90 g/L without transfusion in the past 4 weeks;
• • 13. Signed, written informed consent
• Exclusion Criteria:
• • 1. PSMA-PET "superscan" (i.e. extensive/diffuse PSMA-positive bone involvement);
• • 2. 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;
• • 3. 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);
• • 4. Prior radiopharmaceutical therapy;
• • 5. 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;
• • 6. Active malignancy other than prostate cancer;
• • 7. Patients who are sexually active and not willing/able to use medically acceptable forms of barrier contraception;
• • 8. Any other condition, diagnosis or finding that may in the investigator's opinion interfere with trial conduct;
• • 9. Known hypersensitivity to 177Lu-PSMA-617 or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.