On March 28, 2025, the Food and Drug Administration expanded the indication for lutetium Lu 177 vipivotide tetraxetan (Pluvicto, Novartis Pharmaceuticals Corporation) to include adults with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy.
Patients with previously treated mCRPC should be selected for Pluvicto using Locametz (active ingredient gallium Ga 68 gozetotide) or another approved PSMA positron emission tomography (PET) product based on PSMA expression in tumors.
Full prescribing information for Pluvicto will be posted on Drugs@FDA.
Efficacy and Safety
Efficacy was evaluated in PSMAfore (NCT04689828), a randomized, multicenter, open-label trial enrolling 468 patients with PSMA-positive mCRPC and progression on one ARPI, who the investigator considered appropriate for delay of taxane-based chemotherapy. Patients were randomized (1:1) to receive lutetium Lu 177 vipivotide tetraxetan (7.4 GBq [200 mCi] every 6 weeks for 6 doses) or a change in ARPI. Patients who progressed on the ARPI arm were allowed to crossover to the experimental therapy.
The major efficacy outcome was radiographic progression-free survival (rPFS) by blinded independent central review. Overall survival (OS) was an additional efficacy outcome. Median rPFS was 9.3 months (95% confidence interval [CI]: 7, not estimable) in the lutetium Lu 177 vipivotide tetraxetan arm and 5.6 months (95% CI: 4, 6) in the ARPI arm (hazard ratio [HR] 0.41 [95% CI: 0.29, 0.56]; p-value <0.0001). Median OS was 24.5 months (95% CI: 19.5, 28.9) and 23.1 months (95% CI: 19.6, 25.5) in the respective arms (HR 0.91 [95% CI: 0.72, 1.14]; p-value was not statistically significant). Sixty percent (n=141) of patients who were randomized to receive a change in ARPI crossed over to receive lutetium Lu 177 vipivotide tetraxetan after progression.
Adverse reactions were consistent with prior experience with lutetium Lu 177 vipivotide tetraxetan. Treatment with lutetium Lu 177 vipivotide tetraxetan may result in risk from radiation exposure, myelosuppression, and renal toxicity.
The recommended lutetium Lu 177 vipivotide tetraxetan dose is 7.4 GBq (200 mCi) intravenously every 6 weeks for 6 doses, or until disease progression or unacceptable toxicity.
Expedited Programs
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
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