FDA Approves Lutetium Lu 177 Vipivotide Tetraxetan Plus ARPI in mAPMN/S Prostate Cancer

The FDA has approved lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in combination with androgen receptor pathway inhibitor (ARPI) therapy for adults with prostate-specific membrane antigen (PSMA)-positive metastatic androgen pathway modulation-naive or -sensitive (mAPMN/S) prostate cancer, according to the agency.¹

The approval, announced July 31, 2026, is based on findings from the phase 3 PSMAddition trial (NCT04720157), a randomized, multicenter, open-label study that randomly assigned 1144 patients (572 per arm) to receive lutetium Lu 177 vipivotide tetraxetan at 7.4 GBq (200 mCi) every 6 weeks for 6 doses plus an ARPI or an ARPI alone.

The trial met its major efficacy outcome measure of radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group 3-modified RECIST v1.1 criteria, with a statistically significant improvement favoring the combination (HR, 0.72; 95% CI, 0.58-0.90; P =.002); median rPFS was not reached in either arm. Overall survival (OS), an additional efficacy outcome measure, remained immature at the most recent analysis.

Patients with mAPMN/S prostate cancer, a population previously referred to as metastatic hormone-sensitive prostate cancer, should be selected for treatment using gallium Ga 68 gozetotide (Locametz) or another approved PSMA PET product based on tumor PSMA expression, according to the FDA.

Trial Design

Patients enrolled in PSMAddition received an ARPI of the investigator's choice, including abiraterone (Zytiga), apalutamide (Erleada), enzalutamide (Xtandi), or darolutamide (Nubeqa), with treatment in both arms continuing until disease progression or unacceptable toxicity. All patients also received a gonadotropin-releasing hormone agonist or antagonist concurrently or had undergone bilateral orchiectomy. The trial was previously presented in more detail, including secondary efficacy findings and safety data by treatment arm, at the 2025 ESMO Congress.²

Safety Findings

Adverse reactions with the combination were consistent with the established safety profile of lutetium Lu 177 vipivotide tetraxetan. The prescribing information includes warnings and precautions for radiation exposure, myelosuppression, renal toxicity, embryo-fetal toxicity, and infertility.

Dosing and Regulatory Context

The recommended dose of lutetium Lu 177 vipivotide tetraxetan in combination with an ARPI is 7.4 GBq (200 mCi) every 6 weeks for 6 doses, or until disease progression or unacceptable toxicity. The agent originally received FDA approval in March 2022 for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) following prior anticancer therapy, including ARPI therapy and taxane-based chemotherapy; its indication was expanded in March 2025 to include patients with PSMA-positive mCRPC who have received ARPI therapy and are considered appropriate to delay taxane-based chemotherapy. The current review used the FDA's Assessment Aid, a voluntary submission process intended to facilitate the agency's evaluation, and the application was approved 1 month ahead of the FDA goal date.

REFERENCES

1. FDA Approves Lutetium Lu 177 Vipivotide Tetraxetan With Androgen Receptor Pathway Inhibitor Therapy for Metastatic Androgen Pathway Modulation-Naïve or -Sensitive Prostate Cancer. FDA. July 31, 2026. Accessed July 31, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancerhematologic-malignancies-approval-notifications

2. Tagawa ST, Sartor O, Piulats JM, et al. Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA6.