June 2, 2025: “Novartis announced topline results from a pre-specified interim analysis of the Phase III PSMAddition trial.
The trial met its primary endpoint with a statistically significant and clinically meaningful benefit in radiographic progression-free survival (rPFS) with a positive trend in overall survival (OS) in patients with prostate-specific membrane antigen (PSMA)-positive metastatic hormone-sensitive prostate cancer (mHSPC) treated with radioligand therapy (RLT), Pluvicto™ (lutetium (177Lu) vipivotide tetraxetan), in combination with standard of care (SoC) versus SoC alone.
In PSMAddition, the SoC is a combination of androgen receptor pathway inhibitor (ARPI) therapy and androgen deprivation therapy (ADT).
Almost all mHSPC patients ultimately progress to metastatic castration-resistant prostate cancer (mCRPC).
There is a need for additional treatment options with novel mechanisms of action that further delay progression, prolong OS and improve disease control compared to the current SoC, while showing a favorable safety and tolerability profile.
“The progression from metastatic hormone-sensitive prostate cancer to castration-resistant disease remains a formidable challenge that can profoundly impact the survival of patients,” said Shreeram Aradhye, M.D., President, Development and Chief Medical Officer at Novartis.
“These results further strengthen our confidence in Pluvicto as a PSMA-targeted radioligand therapy. Following the recent FDA approval based on the PSMAfore trial in metastatic castration-resistant prostate cancer, these data suggest using it in an earlier disease setting could advance care and address a significant unmet need for hormone-sensitive prostate cancer patients.”
This is the third positive read-out for Pluvicto in a Phase III trial, following the VISION and PSMAfore studies.
Results from PSMAddition in mHSPC show potential for treatment in an earlier setting with Pluvicto, which was recently granted US Food and Drug Administration (FDA) approval for earlier use in mCRPC, based on results from PSMAfore.
Novartis is harnessing the innovation of world-class scientists, strategic partnerships and one of the industry’s most competitive pipelines to explore the potential of new, targeted therapies and precision medicine platforms to address the greatest unmet needs in prostate cancer.
Data will be presented at an upcoming medical meeting and, based on FDA feedback, will be submitted for regulatory review in the second half of the year.
About PSMAddition study
PSMAddition (NCT04720157) is a Phase III, open-label, prospective, 1:1 randomized study comparing the efficacy and safety of Pluvicto in combination with SoC (ARPI + ADT) vs. SoC alone in adult patients with PSMA-positive mHSPC.
Patients randomized to the SoC alone arm are allowed to crossover to receive Pluvicto, upon confirmation of radiographic progression by blinded independent review committee (BIRC) and per the discretion of the treating physician.
The primary endpoint is rPFS, defined as the time to radiographic progression by PCWG3-modified RECIST V1.1 (as assessed by BIRC) or death. The key secondary endpoint of OS is defined as time to death due to any cause.
About Pluvicto™ (INN: lutetium (177Lu) vipivotide tetraxetan)
Pluvicto is an intravenous RLT that combines a targeting compound (a ligand) with a therapeutic radionuclide (a radioactive particle, in this case lutetium-177).
After administration into the bloodstream, Pluvicto binds to PSMA-expressing target cells, including prostate cancer cells that express PSMA, a transmembrane protei.
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 the only PSMA-targeted agent approved for PSMA-positive mCRPC and is the first targeted RLT to demonstrate a clinical benefit for patients with PSMA-positive mHSPC.
Novartis is investigating Pluvicto in earlier stages of disease, including oligometastatic prostate cancer (PSMA-DC, NCT05939414).
Novartis and radioligand therapy (RLT)
Novartis is reimagining cancer care with RLT for patients with advanced cancers. By harnessing the power of targeted radiation and applying it to advanced cancers, RLT is designed to deliver treatment directly to target cells, anywhere in the body.
Novartis is investigating a broad portfolio of RLTs, exploring new isotopes, ligands and combination therapies to look beyond gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and prostate cancer and into breast, colon, lung and pancreatic cancer.
Novartis has established global expertise, with specialized supply chain and manufacturing capabilities across its network of RLT production sites. To support growing demand for RLTs, we have expanded production capabilities in Millburn (NJ), Zaragoza (Spain), Ivrea (Italy) and a state-of-the-art facility in Indianapolis (IN).
In Carlsbad (CA), Novartis is establishing its third US-based RLT manufacturing site to support expanded use of RLTs, create resiliency in its manufacturing network and optimize the delivery of medicines to patients on the West Coast.”
