Phase 2 [177Lu]Lu-PSMA-617 radioligand (PSMA-targeted beta emitter) with intermittent ADT

Mayo Clinic is running a randomized Phase 2 study in low-volume metastatic hormone-sensitive prostate cancer (de novo or recurrent after prior local therapy) testing whether adding [177Lu]Lu-PSMA-617 (lutetium Lu 177 vipivotide tetraxetan; a PSMA-targeted radioligand that delivers tumor-localized beta radiation) improves outcomes versus intermittent androgen deprivation therapy (iADT) alone. All arms use leuprolide acetate (a GnRH agonist that suppresses testicular androgen production) given intermittently, and a second randomization layer adds abiraterone acetate plus prednisone in some arms; abiraterone (Johnson & Johnson’s Janssen) inhibits CYP17 to block androgen synthesis, while prednisone is included to mitigate mineralocorticoid-related toxicity and support tolerability. The trial incorporates PSMA PET/CT (selection/response) and SPECT (dosimetry/uptake readouts), aligning with radiopharmaceutical development needs. Clinically, today’s typical care for low-volume mHSPC is continuous ADT plus an androgen receptor pathway inhibitor (often abiraterone, enzalutamide, or apalutamide) with metastasis-directed RT considered in select oligometastatic cases; this trial asks whether earlier PSMA-targeted radioligand intensification can deepen remission and potentially enable longer off-therapy intervals than iADT alone. The commercial/scientific angle is upstreaming Novartis’s Pluvicto-class PSMA radioligand strategy from mCRPC into earlier, lower-burden disease where PSMA targeting may be especially efficient.