FDA Approves Lutetium Lu 177 Vipivotide Tetraxetan Plus ARPI for PSMA-Positive Metastatic Hormone-Sensitive Prostate Cancer

Clinical Summary:

• Based on results from the phase 3 PSMAddition trial, the FDA has approved lutetium Lu 177 vipivotide tetraxetan in combination with androgen receptor pathway inhibitor therapy for patients with PSMA-positive metastatic hormone-sensitive prostate cancer.
• The addition of lutetium Lu 177 vipivotide tetraxetan significantly improved radiographic progression-free survival, with a safety profile consistent with prior findings. 
• This approval expands the use of PSMA-targeted radioligand therapy to an earlier stage of metastatic prostate cancer, offering a radioligand therapy option before the development of castration-resistant disease in appropriately selected patients.

Based on results from the phase 3 PSMAddition trial, the US Food and Drug Administration (FDA) approved lutetium Lu 177 vipivotide tetraxetan (Pluvicto; Novartis) in combination with androgen receptor pathway inhibitor (ARPI) therapy for patients with prostate-specific membrane antigen (PSMA)-positive metastatic metastatic hormone-sensitive prostate cancer. The decision marks an expansion of the radioligand therapy into an earlier treatment setting for patients whose tumors demonstrate PSMA expression.

In this multicenter, open-label trial, 1,144 patients were randomized 1:1 to receive either 7.4 GBq (200 mCi) lutetium Lu 177 vipivotide tetraxetan every 6 weeks for 6 doses in combination with an investigator-selected ARPI (n = 572) or ARPI therapy alone (n = 572). Permitted ARPIs included abiraterone, apalutamide, enzalutamide, darolutamide, or another approved ARPI. All patients also received medical or surgical castration.

The primary end point was radiographic progression-free survival (rPFS) as assessed via blinded independent central review according to Prostate Cancer Working Group 3-modified RECIST version 1.1 criteria. Key secondary end points included overall survival (OS) and safety. 

At analysis, the addition of lutetium Lu 177 vipivotide tetraxetan significantly improved rPFS compared with ARPI therapy alone (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.58 to 0.9; P = .002). Median rPFS had not yet been reached in either treatment arm at the time of analysis. OS data were immature and remains under evaluation. Safety was consistent with prior findings. 

The recommended dose of lutetium Lu 177 vipivotide tetraxetan when combined with ARPI therapy is 7.4 GBq (200 mCi) every 6 weeks for up to 6 doses, or until disease progression or unacceptable toxicity. 

Patient selection should be based on PSMA imaging using Locametz (gallium Ga 68 gozetotide) or another FDA-approved PSMA positron emission tomography (PET) imaging agent.

Source:

US Food and Drug Administration. FDA approves lutetium Lu 177 vipivotide tetraxetan with androgen receptor pathway inhibitor therapy for metastatic androgen pathway modulation-naïve or -sensitive prostate cancer. Accessed on August 3, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lutetium-lu-177-vipivotide-tetraxetan-androgen-receptor-pathway-inhibitor-therapy