General Information

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) injection is a radioligand therapeutic agent, which means it is a type of precision cancer treatment combining a targeting compound (ligand) with a therapeutic radioisotope (a radioactive particle).

Pluvicto is specifically indicated for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.

Pluvicto is supplied as an injection for intravenous administration. 

• Select patients with previously treated mCRPC for treatment with Pluvicto using Locametz or another approved PSMA-11 imaging agent based on PSMA expression in tumors. 
• The recommended Pluvicto dosage is 7.4 GBq (200 mCi) intravenously every 6 weeks for up to 6 doses, or until disease progression, or unacceptable toxicity.

Mechanism of Action

Lutetium Lu 177 vipivotide tetraxetan is a radioligand therapeutic agent. The active moiety of lutetium Lu 177 vipivotide tetraxetan is the radionuclide lutetium-177 which is linked to a moiety that binds to PSMA, a transmembrane protein that is expressed in prostate cancer, including mCRPC. Upon binding of lutetium Lu 177 vipivotide tetraxetan to PSMA-expressing cells, the beta-minus emission from lutetium-177 delivers radiation to PSMA-expressing cells, as well as to surrounding cells, and induces DNA damage which can lead to cell death.

In other words, after administration into the bloodstream, Pluvicto binds to target cells, including prostate cancer cells that express PSMA, a transmembrane protein. Once bound, energy emissions from the radioisotope damage the target cells and nearby cells disrupting their ability to replicate and/or triggering cell death.

Side Effects

Adverse effects associated with the use of Pluvicto may include, but are not limited to, the following:

• fatigue
• dry mouth
• nausea
• anemia
• decreased appetite
• constipation
• laboratory abnormalities, including decreased lymphocytes, decreased hemoglobin, decreased leukocytes, decreased platelets, decreased calcium, and decreased sodium

Clinical Trial Results

FDA approval of Pluvicto is based on the results of the Phase 3 VISION trial. This international, prospective, randomized, open-label, multicenter study assessed the efficacy and safety of Pluvicto (lutetium Lu 177 vipivotide tetraxetan) (7.4 GBq administered by IV infusion every 6 weeks for a maximum of 6 cycles) plus investigator-chosen standard of care (SOC) in the investigational arm, versus SOC in the control arm. A total of 831 patients were enrolled. Participants treated with Pluvicto plus SOC had a 38% reduction in risk of death and a statistically significant reduction in the risk of radiographic disease progression or death (rPFS) compared to SOC alone. In addition, about a third (30%) of patients with evaluable disease at baseline demonstrated an overall response (per RECIST 1.1) with Pluvicto plus SOC, compared to 2% in the SOC alone arm.