Evidence Grade A — Regulatory approved. 18 published studies. 34 registered clinical trials.
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Lutetium Lu-177 vipivotide tetraxetan (sold as Pluvicto) is a targeted radiation treatment for advanced prostate cancer that has stopped responding to hormone therapy and chemotherapy. Like Lutathera, it uses a molecular homing system — but instead of finding neuroendocrine tumour receptors, it seeks out PSMA, a protein found at very high levels on prostate cancer cells. It is given as six intravenous infusions, six weeks apart.
Lutetium Lu-177 Vipivotide Tetraxetan is also known by these brand and alternate names:
18 published studies: 11 human, 0 animal, 0 in-vitro, 9 reviews
Pluvicto is marketed by Novartis (approved March 2022) for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in adults who have already received hormone-targeting therapy and taxane chemotherapy. Administered as six intravenous infusions every 6 weeks.
The VISION trial showed Pluvicto extended overall survival by 4 months (15.3 versus 11.3 months) and more than doubled the time before disease worsened compared to standard care alone. Patients must have PSMA-positive tumours confirmed by a companion PET scan before treatment. The PSMAfore trial subsequently showed benefit in patients who had not yet received chemotherapy, potentially expanding the eligible population. Supply constraints limited availability in the first year after approval.
PSMA is a protein found on the surface of prostate cancer cells at concentrations 100 to 1,000 times higher than on normal tissue, and its expression increases as the cancer becomes more aggressive. Pluvicto's targeting molecule binds to PSMA's active site with high precision. Once bound, the entire complex is pulled inside the cancer cell, where the lutetium-177 emits targeted beta radiation that damages the cell's DNA. The radiation's short range (less than 1mm mean penetration) focuses the destructive energy on the tumour while sparing most surrounding tissue.
The VISION trial showed Pluvicto extended overall survival by 4 months (15.3 versus 11.3 months) and more than doubled the time before disease worsened in men with heavily pre-treated prostate cancer. Patients must have PSMA-positive tumours confirmed by a companion PET scan before treatment can begin. A subsequent trial (PSMAfore) showed benefit in patients who had not yet received chemotherapy, potentially expanding the eligible population substantially. Another trial (PSMAddition) is studying use even earlier, in combination with standard hormone therapy. The main side effects include anaemia, fatigue, dry mouth, and bone marrow suppression, with a small long-term risk of secondary blood cancers. Supply constraints limited availability in the first year after approval but have since improved.
PeptideTrace tracks 34 registered clinical trials for Lutetium Lu-177 Vipivotide Tetraxetan sourced from ClinicalTrials.gov.
PULSE Registry: for Patients Receiving Lutetium (177Lu) Vipivotide Tetraxetan
177^Lu-PSMA-617 in Combination With Sipuleucel-T for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Real-world Use of Lutetium (177Lu) Vipivotide Tetraxetan in China(PSMAreal CN)
Alpha-Emitting Radionuclide or Beta-Emitting Radionuclide With Metastasis-Directed Stereotactic Body Radiotherapy for the Treatment of Recurrent, Oligometastatic Prostate Adenocarcinoma
A Phase Ib/II Open-label Study of AMO959 With Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) in Combination With ARPI in Adult Participants With PSMA-positive mCRPC
FDA ORIG 1
EMA Marketing Authorisation
FDA SUPPL 24
FDA SUPPL 21
Lu-177 vipivotide tetraxetan is a PSMA-targeted radioligand: glutamate-urea-lysine PSMA-binding motif conjugated via DOTA chelator to Lu-177. Targets PSMA/FOLH1 overexpressed on prostate cancer cells. IV 7.4 GBq q6w x6 doses. Internalizes via receptor-mediated endocytosis.
Vipivotide motif binds PSMA enzymatic active site with high affinity. PSMA overexpressed ~100-1,000-fold on prostate cancer cells vs. normal epithelium, increasing in mCRPC. After internalization, Lu-177 delivers targeted beta-radiation (Emax 0.497 MeV, mean penetration ~0.67 mm) causing DNA breaks and apoptosis. Crossfire effect irradiates PSMA-negative neighbors.
Marketed as Pluvicto. Approved March 23, 2022. VISION (Phase III; N=831): rPFS 8.7 vs. 3.4 months (HR 0.40, P<0.001); OS 15.3 vs. 11.3 months (HR 0.62, P<0.001). ORR 51% in measurable disease. PSMAfore: superior to ARPI change in taxane-naive mCRPC. Indication: PSMA-positive mCRPC after ARPI and taxane.
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