The Food and Drug Administration (FDA) has approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan) for the treatment of adults 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 a radioligand therapeutic agent containing the active moiety, lutetium-177, which binds to prostate-specific membrane antigen (PSMA), a transmembrane protein that is expressed in prostate cancer. Once bound, the beta-minus emission from lutetium-177 delivers radiation to PSMA-expressing cells as well as surrounding cells, and induces DNA damage resulting in cell death. 

The approval was based on data from the multicenter, randomized, open-label phase 3 VISION study (ClinicalTrials.gov Identifier: NCT03511664), which evaluated the efficacy and safety of Pluvicto in men with progressive, PSMA-positive mCRPC who were previously treated with androgen receptor pathway inhibition and taxane-based chemotherapy. Patients were randomly assigned 2:1 to receive either Pluvicto 7.4 GBq (200 mCi) intravenously every 6 weeks for up to a total of 6 doses plus best standard of care (BSoC; n=551) or BSoC alone (n=280). 

The coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS), assessed by blinded independent central review (BICR) per Prostate Cancer Working Group 3 (PCWG3) criteria. A key secondary endpoint was the overall response rate (ORR), assessed by BICR per RECIST v1.1.

Results demonstrated that treatment with Pluvicto plus BSoC improved OS, with a 38% reduction in risk of death compared with BSoC alone (hazard ratio [HR] 0.62; 95% CI, 0.52-0.74; P <.001). Median OS was 15.3 months (95% CI, 14.2-16.9) in the Pluvicto plus BSoC arm compared with 11.3 months (95% CI, 9.8-13.5) in the BSoC arm. Interpretation of the magnitude of the rPFS effect was limited due to a high degree of censoring from early drop out in the control arm.

Additionally, among 319 evaluable patients in the Pluvicto plus BSoC arm, the ORR was 30% (95% CI, 25-35), of which 6% achieved complete response (CR) and 24% achieved partial response (PR). Among 120 evaluable patients in the BSoC arm, the ORR was 2% (95% CI, 0-6), of which none achieved CR and 2% achieved PR.

The most common adverse reactions (incidence at least 20%) reported for Pluvicto were fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. The most common laboratory abnormalities (incidence at least 30%) included decreased lymphocytes, decreased hemoglobin, decreased leukocytes, decreased platelets, decreased calcium, and decreased sodium.

Pluvicto is supplied as a 30mL single-dose vial containing 1000 MBq/mL (27 mCi/mL) of lutetium Lu 177 vipivotide tetraxetan. The product is expected to be available in the coming weeks.

The FDA also approved Locametz (gallium Ga 68 gozetotide), a radioactive diagnostic agent for positron emission tomography of PSMA-positive lesions, including selection of patients with metastatic prostate cancer for whom lutetium Lu 177 vipivotide tetraxetan PSMA-directed therapy is indicated.

References

  1. Novartis Pluvicto approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer. News release. Novartis Pharma AG. Accessed March 24, 2022. https://www.globenewswire.com/news-release/2022/03/23/2408996/0/en/Novartis-Pluvicto-approved-by-FDA-as-first-targeted-radioligand-therapy-for-treatment-of-progressive-PSMA-positive-metastatic-castration-resistant-prostate-cancer.html
  2. FDA approves Pluvicto for metastatic castration-resistant prostate cancer. News release. March 23, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer
  3. Pluvicto. Package insert. Novartis Pharmaceuticals Corporation; 2022. Accessed March 23, 2022. https://www.novartis.us/sites/www.novartis.us/files/pluvicto.pdf