FDA approves lutetium Lu 177 vipivotide tetraxetan with androgen receptor pathway inhibitor therapy for metastatic androgen pathway modulation-naïve or -sensitive prostate cancer

Regulatory approval: On July 31, 2026, the FDA approved lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in combination with androgen receptor pathway inhibitor (ARPI) therapy for adults with PSMA-positive metastatic androgen pathway modulation-naïve or -sensitive prostate cancer. Approval was supported by the open-label, randomized PSMAddition trial showing a statistically significant rPFS improvement versus ARPI alone (HR 0.72; p=0.002); median rPFS was not reached. OS data were immature at the time of analysis.

FDA approval (July 31, 2026)

The FDA approved lutetium Lu 177 vipivotide tetraxetan (Pluvicto; Novartis) with ARPI therapy for adults with PSMA-positive metastatic androgen pathway modulation-naïve or -sensitive prostate cancer (previously termed metastatic hormone-sensitive prostate cancer).

Patient selection: Patients should be selected using Locametz (gallium Ga 68 gozetotide) or another approved PSMA PET product, based on tumor PSMA expression.

Supporting evidence

Efficacy and safety were evaluated in PSMAddition (NCT04720157), a randomized, multicenter, open-label trial in PSMA-positive mAPMN/S prostate cancer. Patients were randomized 1:1 to:

  • Pluvicto 7.4 GBq (200 mCi) every 6 weeks for 6 doses + an investigator’s-choice ARPI (n=572), or
  • ARPI alone (n=572).

ARPIs included abiraterone, apalutamide, enzalutamide, darolutamide, or another ARPI. ARPI could continue until progression or unacceptable toxicity. Patients also received a GnRH agonist/antagonist or had bilateral orchiectomy.

Primary endpoint: rPFS by blinded independent central review (PCWG3-modified RECIST v1.1). The combination showed a statistically significant rPFS improvement vs ARPI alone: HR 0.72 (95% CI 0.58–0.90); p=0.002; median rPFS not reached in either arm. OS data were immature.

Safety and dosing

Adverse reactions were consistent with prior experience; labeling includes warnings for radiation exposure, myelosuppression, renal toxicity, embryo-fetal toxicity, and infertility. Recommended dose: 7.4 GBq every 6 weeks for 6 doses, or until progression or unacceptable toxicity.

The review was conducted under Project Orbis with collaboration from the UK MHRA; other agencies’ reviews were ongoing at the time of the FDA action.

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