Novartis Announces Positive Interim Results for Pluvicto™ in Early-Stage Prostate Cancer, Meeting Primary Endpoint in Phase III PSMAddition Trial

(IN BRIEF) Novartis has announced that its Phase III PSMAddition trial of Pluvicto™ in combination with standard of care (SoC) has met its primary endpoint, showing a significant benefit in radiographic progression-free survival (rPFS) and a positive trend in overall survival (OS) for patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC). The trial’s success paves the way for the potential use of Pluvicto in an earlier disease setting. This development comes after the FDA’s approval of Pluvicto for metastatic castration-resistant prostate cancer (mCRPC), and Novartis will submit the data for regulatory review later this year. The trial results reinforce the critical need for novel treatments that delay progression and improve survival in patients with prostate cancer.

(PRESS RELEASE) BASEL, 2-Jun-2025 — /EuropaWire/ — Novartis has announced positive interim results from the Phase III PSMAddition trial, evaluating the efficacy and safety of Pluvicto™ (lutetium-177 vipivotide tetraxetan) in combination with standard of care (SoC) for patients with prostate-specific membrane antigen (PSMA)-positive metastatic hormone-sensitive prostate cancer (mHSPC). The trial met its primary endpoint with a statistically significant and clinically meaningful benefit in radiographic progression-free survival (rPFS), as well as a positive trend in overall survival (OS). These results suggest that Pluvicto, an FDA-approved radioligand therapy (RLT) for metastatic castration-resistant prostate cancer (mCRPC), may offer significant benefits in an earlier disease setting, highlighting its potential as an effective treatment for hormone-sensitive prostate cancer.

The PSMAddition trial, which involved patients with PSMA-positive mHSPC, demonstrated that Pluvicto in combination with androgen receptor pathway inhibitors (ARPI) and androgen deprivation therapy (ADT) was superior to SoC alone, delivering improved disease control. As nearly all mHSPC patients ultimately progress to mCRPC, there is a growing need for treatments that can delay progression, improve overall survival, and offer better disease control with favorable safety profiles. This study offers new hope for addressing these needs in a population where treatment options have been limited.

Dr. Shreeram Aradhye, President, Development and Chief Medical Officer at Novartis, stated, “The progression from metastatic hormone-sensitive prostate cancer to castration-resistant disease remains a formidable challenge that significantly impacts patient survival. These results strengthen our confidence in Pluvicto as a PSMA-targeted RLT, and suggest that its use in earlier disease stages could significantly advance care for hormone-sensitive prostate cancer patients.”

This positive result from PSMAddition follows two other successful Phase III trials with Pluvicto—VISION and PSMAfore—which further solidify its role in advancing prostate cancer treatment. Based on FDA feedback, Novartis plans to submit these promising data for regulatory review in the second half of 2025. The findings will also be presented at an upcoming medical meeting.

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 mHSPC3. 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 physician3. The primary endpoint is rPFS, defined as the time to radiographic progression by PCWG3-modified RECIST V1.1 (as assessed by BIRC) or death3. The key secondary endpoint of OS is defined as time to death due to any cause3.

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)5,7. After administration into the bloodstream, Pluvicto binds to PSMA-expressing target cells, including prostate cancer cells that express PSMA, a transmembrane protein5,7. Once bound, energy emissions from the radioisotope damage the target cells and nearby cells, disrupting their ability to replicate and/or triggering cell death7. 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 mHSPC1. 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 body8,9. 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.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “may,” “could,” “trend,” “potentially,” “upcoming,” “progression,” “progress,” “investigating,” “investing,” “look beyond,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for Pluvicto, or regarding potential future revenues from Pluvicto. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that Pluvicto will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that Pluvicto will be commercially successful in the future. In particular, our expectations regarding Pluvicto could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach nearly 300 million people worldwide.

Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.

References

1. Data on file.
2. Pluvicto [prescribing information]. Millburn, NJ: Advanced Accelerator Applications USA, Inc.; 2025.
3. An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC (PSMAddition). ClinicalTrials.gov identifier: NCT04720157. Updated March 5, 2025. Accessed June 2, 2025. https://clinicaltrials.gov/study/NCT04720157.
4. Oing C, Bristow RG. Systemic treatment of metastatic hormone-sensitive prostate cancer—upfront triplet versus doublet combination therapy. ESMO Open 2023l doi: 10.1016/j.esmoop.2023.101194
5. Sartor O, J. de Bono KN, Chi K, et al. Lutetium-177–PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. NEJM 2021; doi: 10.1056/NEJMoa2107322.
6. Morris M, Castellano D, Herrmann K, et al. 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. The Lancet 2024; doi: 10.1016/S0140-6736(24)01653-2.
7. University of Chicago Medicine. Lutetium-177 PSMA Therapy for Prostate Cancer (Pluvicto). Accessed June 18, 2024. https://www.uchicagomedicine.org/cancer/types-treatments/prostate-cancer/treatment/lutetium-177-psma-therapy-for-prostate-cancer.
8. Jadvar H. Targeted Radionuclide Therapy: An Evolution Toward Precision Cancer Treatment [published correction appears in AJR Am J Roentgenol. 2017 Oct;209(4):949. doi: 10.2214/AJR.17.18875]. AJR Am J Roentgenol. 2017;209(2):277-288. doi:10.2214/AJR.17.18264
9. Jurcic JG, Wong JYC, Knoc SJ, et al. Targeted radionuclide therapy. In: Tepper JE, Foote RE, Michalski JM, eds. Gunderson & Tepper’s Clinical Radiation Oncology. 5th ed. Elsevier, Inc. 2021;71(3):209-249

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SOURCE: Novartis