Phase 2 Prospective Trial of Retreatment with [¹⁷⁷Lu]Lu-PSMA-617 Molecular Radiotherapy for Metastatic...

Area of Science:

• Nuclear Medicine
• Oncology
• Radiopharmaceutical Therapy

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) treatment with [177Lu]Lu-PSMA-617 is approved but not curative.
• Patients often experience disease progression after initial response, facing limited subsequent treatment options.
• Retrospective data suggest retreatment with [177Lu]Lu-PSMA-617 may be beneficial for select patients.

Purpose of the Study:

• To evaluate the efficacy and safety of [177Lu]Lu-PSMA-617 rechallenge therapy in mCRPC patients who previously responded well.
• To assess overall survival (OS) at 12 months as the primary endpoint.
• To investigate secondary endpoints including adverse events, PSA response, progression-free survival, and quality of life.

Main Methods:

• RE-LuPSMA is a phase 2, single-arm, single-center, open-label clinical trial.
• Enrolls 40 mCRPC patients with progressive disease after 4-6 cycles of [177Lu]Lu-PSMA-617 and a ≥50% PSA decrease.
• Participants receive up to 6 additional cycles of [177Lu]Lu-PSMA-617 (7.4 GBq every 6 weeks).

Main Results:

• The study is designed with 80% power to detect a 12-month OS rate of 71% versus a null hypothesis of 50%.
• Primary endpoint: 12-month overall survival from the start of rechallenge therapy.
• Secondary endpoints include PSA response rates, progression-free survival (biochemical and radiographic), and quality of life.

Conclusions:

• The RE-LuPSMA trial aims to provide crucial data on the feasibility and outcomes of [177Lu]Lu-PSMA-617 retreatment.
• Positive results could establish rechallenge therapy as a viable option for mCRPC patients with recurrent disease after initial response.
• This study addresses an unmet need for effective salvage therapies in advanced prostate cancer.