Lu-PSMA-617

Lu-PSMA-617, 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).[1][2] Lutetium (177Lu) vipivotide tetraxetan is a targeted radioligand therapy.[2][3]

The most common adverse reactions include fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation.[2][4]

Lu-PSMA-617 is a radioconjugate composed of 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.[5] Upon intravenous administration of Lu-PSMA-617, it targets and binds to PSMA-expressing tumor cells.[5] Upon binding, PSMA-expressing tumor cells are destroyed by 177Lu through the specific delivery of beta particle radiation.[5] 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.[5]

Lu-PSMA-617 was approved for medical use in the United States in March 2022,[2][6] and in the European Union in December 2022.[4] The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[7][8]

## Contents

* 1 Medical uses
* 2 History
* 3 Society and culture
* 3.1 Regulatory status
* 4 References

## Medical uses

Lu-PSMA-617 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.[1]

In March 2025, the US Food and Drug Administration expanded the indication for Lu-PSMA-617 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.[9]

## History

In 2006, scientists from Purdue University designed a targeting ligand that bound with high affinity and specificity to PSMA on prostate cancer cells and patented[10][11] 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 German Cancer Research Center and University Hospital Heidelberg improved the drug's affinity, patented,[12] 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[13] and Endocyte together with the above two sets of patents was acquired by Novartis in 2018.[14]

Efficacy and safety was initially investigated as a compassionate access treatment in Germany with high tumor targeting and low doses to normal organs.[15] 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.[16] The ANZUP co-operative trials conducted the first randomized, multicentre trial comparing lutetium vipivotide tetraxetan to cabazitaxel chemotherapy.[17]

Efficacy was evaluated in VISION,[18] 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.[2] All participants received a GnRH analog or had prior bilateral orchiectomy.[2] Participants were required to have received at least one androgen receptor pathway inhibitor, and 1 or 2 prior taxane-based chemotherapy regimens.[2] 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.[2]

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.[9] 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.[9] Participants who progressed on the androgen receptor pathway inhibitor arm were allowed to crossover to the experimental therapy.[9]

The US Food and Drug Administration granted the application for Lu-PSMA-617 priority review and breakthrough therapy designations.[2]

## Society and culture

### Regulatory status

In October 2022, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Pluvicto, intended for the treatment of prostate cancer.[19] The applicant for this medicinal product was Novartis Europharm Limited.[19] Lu-PSMA-617 was approved for medical use in the European Union in December 2022.[4][20]

## References

1. ↑ 1.0 1.1 Cite error: Invalid `<ref>` tag; no text was provided for refs named `Pluvicto FDA label`
2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "FDA approves Pluvicto for metastatic castration-resistant prostate cancer". 23 March 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer. This article incorporates text from this source, which is in the public domain.
3. ↑ "Radiolabeled PSMA Inhibitors". Cancers 13 (24): 6255. December 2021. doi:10.3390/cancers13246255. PMID 34944875.
4. ↑ 4.0 4.1 4.2 Cite error: Invalid `<ref>` tag; no text was provided for refs named `Pluvicto EPAR`
5. ↑ 5.0 5.1 5.2 5.3 "Lutetium Lu 177 Vipivotide Tetraxetan (Code C148145)". NCI Thesaurus. 28 February 2022. https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI Thesaurus&code=C148145. This article incorporates text from this source, which is in the public domain.
6. ↑ "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.
7. ↑ "Advancing Health Through Innovation: New Drug Therapy Approvals 2022". 10 January 2023. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/new-drug-therapy-approvals-2022. This article incorporates text from this source, which is in the public domain.
8. ↑ (PDF) ﻿New Drug Therapy Approvals 2022﻿ (Report). January 2024. https://www.fda.gov/media/164429/download. Retrieved 14 January 2024. This article incorporates text from this source, which is in the public domain.
9. ↑ 9.0 9.1 9.2 9.3 "FDA expands Pluvicto's metastatic castration-resistant prostate cancer indication". 28 March 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication. This article incorporates text from this source, which is in the public domain.
10. ↑ Low PS, Kularatne SA, "PSMA binding ligand-linker conjugates and methods for using", US patent 11318121, issued 3 May 2022, assigned to Purdue Research Foundation
11. ↑ Low PS, Kularatne SA, "PSMA binding ligand-linker conjugates and methods for using", US patent 10406240, issued 10 September 2019, assigned to Purdue Research Foundation
12. ↑ 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", US patent 20160228587, published 11 August 2016, assigned to Deutsches Krebsforschungszentrum DKFZ, Universitaet Heidelbergand Molecular Insight Pharmaceuticals Inc.
13. ↑ "Endocyte Announces Exclusive License of Phase 3 Ready PSMA-Targeted Radioligand Therapy for Development in Prostate Cancer". https://www.isotope.com/corporate-overview/news.cfm?nid=Endocyte Announces Exclusive Worldwide License of Phase 3 Ready PSMA-Targeted Radioligand Therapy for Development in Prostate Cancer.
14. ↑ "Novartis inks $2.1B Endocyte buyout, furthering radiotherapy push" (in en). 18 October 2018. https://www.fiercebiotech.com/biotech/novartis-inks-2-1b-endocyte-buyout-furthering-radiotherapy-push.
15. ↑ "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. November 2015. doi:10.2967/jnumed.115.161299. PMID 26294298.
16. ↑ "[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. June 2018. doi:10.1016/S1470-2045(18)30198-0. PMID 29752180.
17. ↑ "[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. February 2021. doi:10.1016/s0140-6736(21)00237-3. PMID 33581798.
18. ↑ Clinical trial number NCT03511664 for "Study of 177Lu-PSMA-617 In Metastatic Castrate-Resistant Prostate Cancer (VISION)" at ClinicalTrials.gov.
19. ↑ 19.0 19.1 "Pluvicto: Pending EC decision". 13 October 2022. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/pluvicto. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
20. ↑ "Pluvicto Product information". https://ec.europa.eu/health/documents/community-register/html/h1703.htm.

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