On December 5, 2022 Novartis announced the pivotal Phase III PSMAfore study with PluvictoTM (INN: lutetium (177Lu) vipivotide tetraxetan), a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy, met its primary endpoint (Press release, Novartis, DEC 5, 2022, View Source [SID1234624790]). Pluvicto demonstrated a statistically significant and clinically meaningful improvement in radiographic progression-free survival (rPFS) in patients with PSMA–positive metastatic castration- resistant prostate cancer (mCRPC) after treatment with androgen-receptor pathway inhibitor (ARPI) therapy, compared to a change in ARPI1. No unexpected safety findings were observed in PSMAfore; data are consistent with the already-well established safety profile of Pluvicto.
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This is the second positive read-out for Pluvicto in a Phase III trial following the VISION study, where patients with PSMA–positive mCRPC who received Pluvicto plus standard of care after being treated with ARPI and taxane-based chemotherapy had a statistically significant reduction in risk of death1,3. The PSMAfore results continue to support the important role of Pluvicto1 in treating patients with prostate cancer. The Phase III data will be presented at an upcoming medical meeting and discussed with the US Food and Drug Administration (FDA) in 2023 for regulatory approval.
"With the announcement of these positive topline Phase III results, Pluvicto becomes the first PSMA-targeted radioligand therapy to demonstrate significant and clinically meaningful benefits for people living with this type of prostate cancer who have not received taxane- based chemotherapy," said Shreeram Aradhye, M.D., President, Global Drug Development and Chief Medical Officer, Novartis. "We look forward to discussing the data with healthcare authorities in order to bring this innovative new early treatment option to many more prostate cancer patients sooner after their diagnosis."
The vast majority of patients diagnosed with CRPC already present with metastases at time of diagnosis4, patients with metastatic prostate cancer have an approximate 3 in 10 chance of surviving 5 years5. Despite recent advances, outcomes for those who progress after standard of care second-generation ARPI remain poor, and there is an urgent need for new targeted treatment options to help improve long-term outcomes6,7,8,9.
Pluvicto is already approved for treatment in adult patients with PSMA–positive mCRPC who have been treated with ARPI and taxane-based chemotherapy in the United States and several other countries10-12.
About the PSMAfore Study
PSMAfore is a Phase III, open-label, multi-center, 1:1 randomized study comparing the efficacy and safety of Pluvicto to a change in ARPI in patients with PSMA–positive mCRPC13. Patients enrolled must have progressed only once after receiving a second-generation ARPI13. There were 469 participants enrolled in the study13. The primary endpoint is rPFS, defined as the time from randomization to radiographic progression by PCWG3-modified RECIST v1.1 (as assessed by blinded independent central review) or death13. Evaluation of overall survival, the key secondary endpoint, is ongoing as data remain immature.
About PluvictoTM (lutetium (177Lu) vipivotide tetraxetan)
Pluvicto is an intravenous radioligand therapy combining a targeting compound (a ligand) with a therapeutic radionuclide (a radioactive particle, in this case lutetium-177)3. After administration into the bloodstream, Pluvicto binds to target cells, including prostate cancer cells that express PSMA, a transmembrane protein3. Once bound, energy emissions from the radioisotope damage the target cells and nearby cells, disrupting their ability to replicate and/or triggering cell death.
Pluvicto is approved in the US and other countries to treat adults with a type of advanced cancer called PSMA–positive mCRPC and who have already been treated with other anticancer treatments (ARPI and taxane-based chemotherapy)10-12. More specifically, in March 2022, the United States Food and Drug Administration (US FDA) approved Pluvicto10. In August and September 2022, the Medicines and Healthcare products Regulatory Agency (MHRA) and Health Canada approved Pluvicto in Great Britain and Canada, respectively11,12. In October 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the granting of a marketing authorization for Pluvicto14. These regulatory decisions are supported by the results from the pivotal Phase III VISION study, where patients with pre-treated PSMA– positive mCRPC who received Pluvicto plus standard of care had a statistically significant reduction in the risk of death; both alternate primary endpoints of radiographic progression free survival and overall survival were met.
Novartis is also evaluating opportunities to investigate Pluvicto radioligand therapy in earlier stages of prostate cancer.