Phase 2 lutetium Lu 177 vipivotide tetraxetan PSMA-targeted radioligand with EBRT in high-risk localized prostate cancer.

This Phase 2, open-label, randomized study at Johns Hopkins (Sidney Kimmel Comprehensive Cancer Center) tests whether adding lutetium Lu 177 vipivotide tetraxetan (also known as 177Lu-PSMA-617; Pluvicto, from Novartis) to definitive external beam radiotherapy can allow a shorter duration of androgen deprivation therapy without sacrificing cancer control. Arm A gives 177Lu-PSMA-617 (a PSMA-directed small-molecule radioligand that delivers beta radiation after binding/internalization in PSMA-expressing prostate cancer) before and during EBRT plus 6 months of ADT, while Arm B uses EBRT plus 24 months of ADT. The core aim is to compare safety/toxicity and early efficacy signals, alongside patient-reported quality of life, because long-term ADT commonly drives fatigue, sexual dysfunction, hot flashes, metabolic changes, and bone loss. The scientific/commercial angle is moving a proven metastatic radioligand platform earlier—into localized, “curative-intent” therapy—where the current standard is EBRT plus long-course ADT (often 18–36 months, sometimes with systemic intensification in select patients), and this tests whether systemic PSMA-radioligand therapy can offset the need for prolonged hormonal suppression.