Pluvicto (lutetium Lu 177 vipivotide tetraxetan)

P2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=40 --> 0 | Trial completion date: Jun 2029 --> May 2026 | Suspended --> Withdrawn | Trial primary completion date: Jun 2027 --> May 2026

P2, N=94, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

Theranostic radiopharmaceutical therapy has moved from niche practice to mainstream oncology, anchored by approvals of lutetium Lu 177 dotatate for somatostatin receptor-positive neuroendocrine tumors and lutetium Lu 177 vipivotide tetraxetan for PSMA-positive prostate cancer. Yet the field's future depends on rigorous clinical trial design, realistic operational planning, and workforce readiness. This review summarizes how theranostics evolved, outlines current regulatory and trial-design yardsticks (including dose optimization and expectations for assessment of late-toxicity), and provides a practical framework for nuclear medicine physicians to assess protocols and prepare their practices for expanding indications and combinations.

Elderly mCRPC patients undergoing 177Lu-PSMA-617 radioligand therapy achieve meaningful PSA50 response rates, with baseline hemoglobin, prior docetaxel exposure, tumor burden, PSMA expression level, and ALP being independent predictors of response. Treatment response is closely associated with improved quality of life and mental health outcomes, with response rates improving with additional therapy cycles. These findings provide evidence-based guidance for precision patient selection, treatment monitoring, and individualized optimization strategies for 177Lu-PSMA-617 therapy.

P1, N=355, Recruiting, Janssen Research & Development, LLC | N=250 --> 355

P2, N=7, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2029 --> Oct 2026 | Trial primary completion date: Apr 2029 --> Oct 2026

P1, N=101, Active, not recruiting, Endocyte | Recruiting --> Active, not recruiting

P3, N=3360, Recruiting, University College, London | N=346 --> 3360

P1/2, N=22, Recruiting, Universitaetsklinikum Essen AR | -> Recruiting | Phase classification: PN/A --> P1/2

P2, N=60, Not yet recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Over a period of 10 y, our center treated 766 patients with prostate cancer using 177Lu-PSMA (177Lu-PSMA-617 or 177Lu-PSMA I&T)...Two patients received complement inhibition with eculizumab, which improved hematologic features without meaningful renal recovery. 177Lu-PSMA-associated TMA is a rare but a potentially severe complication of treatment. The contribution of initial versus cumulative renal absorbed dose remains unclear, and early dosimetry may help identify at-risk patients.

Pathway analysis reveals that p53 upregulation associates with poor PFS and OS, while an activated E2F pathway unexpectedly portends better PFS and OS. These findings support the integration of liquid biopsy proteomics into biomarker-driven mCRPC trials to improve patient stratification.