Lutetium (177Lu) vipivotide tetraxetan

Lutetium (177
Lu) vipivotide tetraxetan
Clinical data
Trade namesPluvicto
Other namesLu-PSMA-617, Lutetium (177Lu) vipivotide tetraxetan, Lutetium Lu 177 vipivotide tetraxetan (USAN US)
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa622063
License data
Pregnancy
category
  • AU: X (High risk)
Routes of
administration		Intravenous
Drug classRadiopharmaceutical
ATC code
Legal status
Legal status
Identifiers
  • Lutetium-177 2-[4-[2-[[4-[[(2S)-1-[[(5S)-5-carboxy-5-[[(1S)-1,3-dicarboxypropyl]carbamoylamino]pentyl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamoyl]cyclohexyl]methylamino]-2-oxoethyl]-7,10-bis(carboxylatomethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC49H71LuN9O16
Molar mass1217.121 g·mol−1
3D model (JSmol)
  • [177Lu+3].OC(=O)CC[C@H](NC(=O)N[C@@H](CCCCNC(=O)[C@H](Cc1ccc2ccccc2c1)NC(=O)[C@@H]3CC[C@@H](CNC(=O)CN4CCN(CC(=O)[O-])CCN(CC(=O)[O-])CCN(CC(=O)[O-])CC4)CC3)C(=O)O)C(=O)O
  • InChI=1S/C49H71N9O16.Lu/c59-40(28-55-17-19-56(29-42(62)63)21-23-58(31-44(66)67)24-22-57(20-18-55)30-43(64)65)51-27-32-8-12-35(13-9-32)45(68)52-39(26-33-10-11-34-5-1-2-6-36(34)25-33)46(69)50-16-4-3-7-37(47(70)71)53-49(74)54-38(48(72)73)14-15-41(60)61;/h1-2,5-6,10-11,25,32,35,37-39H,3-4,7-9,12-24,26-31H2,(H,50,69)(H,51,59)(H,52,68)(H,60,61)(H,62,63)(H,64,65)(H,66,67)(H,70,71)(H,72,73)(H2,53,54,74);/q;+3/p-3/t32-,35-,37-,38-,39-;/m0./s1/i;1+2
  • Key:RSTDSVVLNYFDHY-BGOLSCJMSA-K

Lutetium (177Lu) vipivotide tetraxetan (INN), sold under the brand name Pluvicto, is a radiopharmaceutical medication used for the treatment of prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Lutetium (177Lu) vipivotide tetraxetan is a targeted radioligand therapy.

The most common adverse reactions include fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation.

Lutetium (177Lu) vipivotide tetraxetan is a radioconjugate composed of vipivotide tetraxetan (PSMA-617), a human prostate-specific membrane antigen (PSMA)-targeting ligand, conjugated to the beta-emitting radioisotope lutetium-177, with potential antineoplastic activity against PSMA-expressing tumor cells. Upon intravenous administration of Lutetium (177Lu) vipivotide tetraxetan, it targets and binds to PSMA-expressing tumor cells. Upon binding, PSMA-expressing tumor cells are destroyed by 177Lu through the specific delivery of beta particle radiation. PSMA, a tumor-associated antigen and type II transmembrane protein, is expressed on the membrane of prostatic epithelial cells and overexpressed on prostate tumor cells.

Lutetium (177Lu) vipivotide tetraxetan was approved for medical use in the United States in March 2022, and in the European Union in December 2022. The US Food and Drug Administration considers it to be a first-in-class medication.

Medical uses

Lutetium (177Lu) vipivotide tetraxetan is indicated for the treatment of adults with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy.

In March 2025, the US Food and Drug Administration (FDA) expanded the indication for Lutetium (177Lu) vipivotide tetraxetan to include adults with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer who have been treated with androgen receptor pathway inhibitor therapy and are considered appropriate to delay taxane-based chemotherapy.

In July 2026, the FDA approved lutetium (177Lu) vipivotide tetraxetan in combination with androgen receptor pathway inhibitor therapy for adults 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).

Side effects

The most common adverse reactions include fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation.

The US prescribing information includes warnings and precautions for the risk of radiation exposure, myelosuppression, renal toxicity, embryo-fetal toxicity, and infertility.

History

In 2006, scientists designed a targeting ligand that bound with high affinity and specificity to PSMA on prostate cancer cells and patented its ability to target attached radionuclides such as 177Lu, 99mTc, 68Ga, etc. to prostate cancers. The patents were licensed to Endocyte in 2007. In 2012, scientists at improved the drug's affinity, patented, and licensed to ABX advanced biomedical compounds, a small German pharmaceutical company, for early clinical development. In 2017, the ABX patent was also acquired by Endocyte and Endocyte together with the above two sets of patents was acquired by Novartis in 2018.

Efficacy and safety was initially investigated as a compassionate access treatment in Germany with high tumor targeting and low doses to normal organs. Physician-scientists from the Peter MacCallum Cancer Centre conducted a phase 2 trial demonstrating high response rates, low toxicity and reduction in pain in men with metastatic castration-resistant cancer who progressed after conventional treatments. The ANZUP co-operative trials conducted the first randomized, multicentre trial comparing lutetium vipivotide tetraxetan to cabazitaxel chemotherapy.

Efficacy was evaluated in VISION, a randomized (2:1), multicenter, open-label trial that evaluated Lu-PSMA-617 plus best standard of care (BSoC) (n=551) or BSoC alone (n=280) in men with progressive, prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer. All participants received a GnRH analog or had prior bilateral orchiectomy. Participants were required to have received at least one androgen receptor pathway inhibitor, and 1 or 2 prior taxane-based chemotherapy regimens. Participants received Lu-PSMA-617 7.4 GBq (200 mCi) every 6 weeks for up to a total of 6 doses plus BSoC or BSoC alone.

Efficacy was evaluated in PSMAfore (NCT04689828), a randomized, multicenter, open-label trial enrolling 468 participants with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer and progression on one androgen receptor pathway inhibitor, who the investigator considered appropriate for delay of taxane-based chemotherapy. Participants were randomized (1:1) to receive Lu-PSMA-617 (7.4 GBq [200 mCi] every six weeks for six doses) or a change in androgen receptor pathway inhibitor. Participants who progressed on the androgen receptor pathway inhibitor arm were allowed to crossover to the experimental therapy.

The US Food and Drug Administration granted the application for Lutetium (177Lu) vipivotide tetraxetan priority review and breakthrough therapy designations.

Efficacy for lutetium (177Lu) vipivotide tetraxetan used with in combination with androgen receptor pathway inhibitor therapy was evaluated in PSMAddition (NCT04720157), a randomized, multicenter, open-label trial in participants with PSMA-positive mAPMN/S prostate cancer. Participants were randomized (1:1) to receive either lutetium (177Lu) vipivotide tetraxetan (7.4 GBq [200 mCi] every 6 weeks for 6 doses) in combination with an androgen receptor pathway inhibitor (n=572) or an androgen receptor pathway inhibitor alone (n=572). The administered androgen receptor pathway inhibitor per investigator's choice included abiraterone, apalutamide, enzalutamide, darolutamide, or another androgen receptor pathway inhibitor. Treatment with androgen receptor pathway inhibitor in both arms could be continued until progressive disease or unacceptable toxicity. Participants received a gonadotropin-releasing hormone agonist or antagonist concurrently or had a bilateral orchiectomy.

Society and culture

Lutetium (177Lu) vipivotide tetraxetan was approved for medical use in the United States in March 2022, and in the European Union in December 2022.

Names

Lutetium (177Lu) vipivotide tetraxetan is the international nonproprietary name and the United States Adopted Name.

Lutetium (177Lu) vipivotide tetraxetan is sold under the brand name Pluvicto.

References

  1. 1 2 "Pluvicto (Lutetium (177Lu) vipivotide tetraxetan)". Therapeutic Goods Administration (TGA). 31 July 2024. Retrieved 12 October 2024.
  2. ↑ "PLUVICTO (Novartis Pharmaceuticals Australia Pty Ltd) : Australian registration". Tga.gov.au. Retrieved 31 October 2026.
  3. ↑ Advanced Accelerator Applications USA. "Pluvicto Product Monograph" (PDF). The Drug and Health Product Register. Government of Canada. Retrieved 12 October 2022.
  4. ↑ "Summary Basis of Decision for Pluvicto". Drug and Health Products Portal. 20 January 2023. Retrieved 10 August 2026.
  5. 1 2 3 4 "Pluvicto- lutetium lu 177 vipivotide tetraxetan injection, solution". DailyMed. 23 March 2022. Archived from the original on 5 April 2022. Retrieved 4 April 2022.
  6. 1 2 3 4 5 6 7 8 9 10 11 12 "FDA approves Pluvicto for metastatic castration-resistant prostate cancer". U.S. Food and Drug Administration (FDA). 23 March 2022. Archived from the original on 24 March 2022. Retrieved 23 March 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  7. 1 2 3 4 5 6 "Pluvicto EPAR". European Medicines Agency. 12 October 2022. Retrieved 21 December 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  8. 1 2 "Pluvicto Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  9. ↑ Neels OC, Kopka K, Liolios C, Afshar-Oromieh A (December 2021). "Radiolabeled PSMA Inhibitors". Cancers. 13 (24): 6255. doi:10.3390/cancers13246255. PMC 8699044. PMID 34944875.
  10. 1 2 3 4 "Lutetium Lu 177 Vipivotide Tetraxetan (Code C148145)". NCI Thesaurus. 28 February 2022. Archived from the original on 15 April 2022. Retrieved 23 March 2022. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ↑ "Novartis Pluvicto approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer" (Press release). Novartis. 23 March 2022. Archived from the original on 23 March 2022. Retrieved 23 March 2022.
  12. ↑ "Advancing Health Through Innovation: New Drug Therapy Approvals 2022". U.S. Food and Drug Administration (FDA). 10 January 2023. Archived from the original on 10 January 2023. Retrieved 22 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  13. ↑ New Drug Therapy Approvals 2022. U.S. Food and Drug Administration (FDA) (Report). January 2024. Archived from the original (PDF) on 14 January 2024. Retrieved 14 January 2024. Public Domain This article incorporates text from this source, which is in the public domain.
  14. 1 2 3 4 "FDA expands Pluvicto's metastatic castration-resistant prostate cancer indication". U.S. Food and Drug Administration (FDA). 28 March 2025. Archived from the original on 28 March 2025. Retrieved 28 March 2025. Public Domain This article incorporates text from this source, which is in the public domain.
  15. 1 2 3 4 5 6 7 "FDA approves lutetium Lu 177 vipivotide tetraxetan with androgen recep". U.S. Food and Drug Administration (FDA). 31 July 2026. Retrieved 10 August 2026. Public Domain This article incorporates text from this source, which is in the public domain.
  16. ↑ "FDA approves Pluvicto® for PSMA+ metastatic hormone-sensitive prostate cancer (mHSPC), advancing potential new standard of care across metastatic disease" (Press release). Novartis. 31 July 2026. Retrieved 10 August 2026.
  17. ↑ US 11318121, Low PS, Kularatne SA, "PSMA binding ligand-linker conjugates and methods for using", issued 3 May 2022, assigned to Purdue Research Foundation
  18. ↑ US 10406240, Low PS, Kularatne SA, "PSMA binding ligand-linker conjugates and methods for using", issued 10 September 2019, assigned to Purdue Research Foundation
  19. ↑ US 20160228587, Eder M, Kopka K, Schäfer M, Bauder-Wüst U, Haberkorn U, Eisenhut M, Mier W, Benesova M, "Labeled inhibitors of prostate specific membrane antigen (psma), their use as imaging agents and pharmaceutical agents for the treatment of prostate cancer", published 11 August 2016, assigned to Deutsches Krebsforschungszentrum DKFZ, Universitaet Heidelberg and Molecular Insight Pharmaceuticals Inc.
  20. ↑ "Endocyte Announces Exclusive License of Phase 3 Ready PSMA-Targeted Radioligand Therapy for Development in Prostate Cancer". www.isotope.com. Archived from the original on 29 April 2019. Retrieved 13 April 2022.
  21. ↑ Taylor PN (18 October 2018). "Novartis inks $2.1B Endocyte buyout, furthering radiotherapy push". Fierce Biotech. Archived from the original on 30 November 2020. Retrieved 13 April 2022.
  22. ↑ Afshar-Oromieh A, Hetzheim H, Kratochwil C, Benesova M, Eder M, Neels OC, et al. (November 2015). "The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions". Journal of Nuclear Medicine. 56 (11): 1697–1705. doi:10.2967/jnumed.115.161299. PMID 26294298. S2CID 23317879.{{cite journal}}: CS1 maint: overridden setting (link)
  23. ↑ Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. (June 2018). "[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study". The Lancet. Oncology. 19 (6): 825–833. doi:10.1016/S1470-2045(18)30198-0. PMID 29752180. S2CID 21674458.{{cite journal}}: CS1 maint: overridden setting (link)
  24. ↑ Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, et al. (February 2021). "[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial". Lancet. 397 (10276): 797–804. doi:10.1016/s0140-6736(21)00237-3. PMID 33581798. S2CID 231885243.{{cite journal}}: CS1 maint: overridden setting (link)
  25. ↑ Clinical trial number NCT03511664 for "Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer (VISION)" at ClinicalTrials.gov.
  26. ↑ World Health Organization (2021). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 85". WHO Drug Information. 35 (1). hdl:10665/340684.
  27. ↑ "STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL : USAN (JK-218) lutetium Lu 177 vipivotide tetraxetan" (PDF). Searchusan.ama-assn.org. Retrieved 31 October 2026.