SILVER SPRING, Md., July 31, 2026
The U.S. Food and Drug Administration (FDA) has approved Novartis’ Pluvicto (lutetium Lu 177 vipivotide tetraxetan) in combination with an androgen receptor pathway inhibitor (ARPI) for the treatment of adults with PSMA-positive metastatic androgen pathway modulation-naïve or -sensitive (mAPMN/S) prostate cancer, previously known as metastatic hormone-sensitive prostate cancer. The approval significantly expands the use of the PSMA-targeted radioligand therapy into an earlier stage of advanced prostate cancer. Patients eligible for treatment must first undergo imaging with Locametz (gallium Ga 68 gozetotide) or another FDA-approved PSMA PET imaging agent to confirm PSMA expression before initiating therapy. The decision marks another important milestone in the growing role of precision radiopharmaceuticals for prostate cancer management.
Phase 3 Trial Demonstrates Significant Improvement in Progression-Free Survival
The FDA approval is supported by results from the global Phase 3 PSMAddition trial (NCT04720157), which enrolled 1,144 patients with PSMA-positive metastatic androgen pathway modulation-naïve or -sensitive prostate cancer. Participants were randomized to receive either Pluvicto plus an androgen receptor pathway inhibitor or ARPI therapy alone. Investigators evaluated radiographic progression-free survival (rPFS) as the primary endpoint using blinded independent central review. The combination therapy demonstrated a statistically significant 28% reduction in the risk of radiographic disease progression or death, achieving a hazard ratio of 0.72 (95% CI: 0.58–0.90; p=0.002) compared with ARPI alone. At the time of analysis, median rPFS had not yet been reached in either treatment arm, while overall survival data remain immature and will continue to be monitored.
Radioligand Therapy Expands Earlier in Advanced Prostate Cancer
Pluvicto is a PSMA-targeted radioligand therapy that delivers lutetium-177 radiation directly to prostate cancer cells expressing prostate-specific membrane antigen (PSMA), minimizing exposure to surrounding healthy tissues. The newly approved regimen recommends administering 7.4 GBq (200 mCi) every six weeks for up to six doses, alongside continued androgen receptor pathway inhibitor therapy, unless disease progression or unacceptable toxicity occurs. Patients in the clinical trial also received gonadotropin-releasing hormone (GnRH) therapy or had previously undergone bilateral orchiectomy as part of standard androgen deprivation treatment. According to the FDA, the safety profile remained consistent with previous clinical experience, with important warnings regarding radiation exposure, myelosuppression, renal toxicity, embryo-fetal toxicity, and potential infertility.
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Approval Strengthens Precision Oncology and PSMA-Targeted Treatment
The latest FDA approval expands access to PSMA-targeted radiopharmaceutical therapy for patients at an earlier stage of metastatic prostate cancer, reflecting continued progress in precision oncology. By combining targeted radioligand therapy with established androgen receptor pathway inhibitors, clinicians now have an additional treatment strategy designed to delay disease progression before patients become resistant to hormone-based therapies. The FDA also completed its review one month ahead of the agency’s target action date, highlighting the significance of the application. With this expanded indication, Novartis further strengthens the clinical role of Pluvicto as a key therapeutic option for PSMA-positive metastatic prostate cancer, supporting more personalized treatment approaches for patients with advanced disease.
Source: Novartis, press release
