FDA approves lutetium Lu 177 vipivotide tetraxetan for PSMA-positive mHSPC

On July 31, 2026, the FDA approved lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in combination with androgen receptor pathway inhibitor (ARPI) therapy for patients with prostate-specific membrane antigen (PSMA)-positive metastatic androgen pathway modulation-naïve or-sensitive (mAPMN/S) prostate cancer, previously referred to as metastatic hormone-sensitive prostate cancer (mHSPC).¹

According to the agency, eligibility for treatment with lutetium Lu 177 vipivotide tetraxetan should be determined using active ingredient gallium Ga 68 gozetotide (Locametz) or another approved PSMA-PET product based on PSMA expression in tumors.

Lutetium Lu 177 vipivotide tetraxetan was previously approved in the US for patients with metastatic androgen pathway modulation-resistant (mAPMR) prostate cancer, also known as metastatic castration-resistant prostate cancer (mCRPC), in both the taxane-naive and post-taxane settings.

“The treatment landscape for mHSPC is evolving, and this approval reflects a growing recognition that earlier treatment intensification matters,” said Michael Morris, MD, Prostate Cancer Section Head, GU Oncology at Memorial Sloan Kettering Cancer Center.² “Having a radioligand therapy available at this stage meaningfully expands the options for physicians and represents real progress for patients.”

Data on lutetium Lu 177 vipivotide tetraxetan

The approval is supported by results from the phase 3 PSMAddition trial (NCT04720157), which demonstrated that adding lutetium Lu 177 vipivotide tetraxetan to ARPI therapy significantly improved radiographic progression-free survival (rPFS) vs ARPI monotherapy (HR, 0.72; 95% CI, 0.58 to 0.90; P = .002). The results were presented at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.³

The study enrolled 1144 patients who were randomly assigned 1:1 to receive 7.4 GBq (200 mCi) lutetium Lu 177 vipivotide tetraxetan for 6 cycles plus androgen deprivation therapy (ADT) and ARPI (n = 572) or to ADT and ARPI alone (n = 572). Patients were eligible for enrollment if they had untreated or minimally treated mHSPC, an ECOG performance status of 0 to 2, at least 1 PSMA-positive metastatic lesion per ⁶⁸Ga-PSMA-11 PET/CT imaging, and were appropriate for ADT plus ARPI.

Baseline characteristics were balanced between the arms. The primary end point was rPFS, with overall survival (OS) as a key secondary end point. Other end points included objective response rate (ORR), time to metastatic castration-resistant prostate cancer (mCRPC), PFS, quality of life, and safety.

At a median follow-up of 23.6 months, the median rPFS has not been reached in either arm. The observed benefit in rPFS was consistent across subgroups.

OS data were immature at the time of data report. However, there was a trend toward improvement in the lutetium Lu 177 vipivotide tetraxetan arm, although the difference did not achieve statistical significance (HR, 0.80; 95% CI, 0.63 to 1.01).

The data presented at ESMO showed improvements across other secondary end points. ORR per RECIST v1.1 was 85.3% (95% CI, 79.9% to 89.6%) in the lutetium Lu 177 vipivotide tetraxetan arm vs 80.8% (95% CI, 74.8% to 85.8%) in the comparator arm. Complete responses were achieved in 57.1% and 42.3% of patients, respectively. More patients in the lutetium Lu 177 vipivotide tetraxetan arm achieved a prostate-specific antigen (PSA) nadir of less than 0.2 ng/mL at 48 weeks, with a rate of 87.4% (95% CI, 83.6% to 90.6%) in the lutetium Lu 177 vipivotide tetraxetan arm vs 74.9% (95% CI, 70.3% to 79.1%) in the comparator arm.

All other secondary end points also favored the lutetium Lu 177 vipivotide tetraxetan arm, including time to PSA progression (HR, 0.42; 95% CI, 0.30 to 0.59); time to symptomatic skeletal event (HR, 0.89; 95% CI, 0.62 to 1.26); time to mCRPC (HR, 0.70; 95% CI, 0.58 to 0.84), and PFS per investigator assessment (HR, 0.64; 95% CI, 0.51 to 0.79).

Regarding safety, grade 3 or higher adverse events (AEs) were reported in 50.7% of patients in the lutetium Lu 177 vipivotide tetraxetan arm and 43% of patients in the comparator arm. The most common all-grade AEs in the treatment arm were dry mouth (45.7%), fatigue (34.8%), nausea (34.2%), hot flush (29.1%), and anemia (27.1%).

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