Adding lutetium (177Lu) vipivotide tetraxetan to SOC improves rPFS in mHSPC

The phase 3 PSMAddition trial (NCT04720157) has met its primary end point, demonstrating that the addition of lutetium (177Lu) vipivotide tetraxetan (177Lu-PSMA-617; Pluvicto) to standard of care (SOC) hormone therapy significantly improved radiographic progression-free survival (rPFS) in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC), Novartis announced in a news release.¹

Novartis plans to submit these data for regulatory review in the second half of 2025.

Data from the study also showed a trend toward improvement in overall survival (OS) with the combination.

In the trial, SOC treatment consisted of an androgen receptor pathway inhibitor (ARPI) and androgen deprivation therapy (ADT).

Lutetium (177Lu) vipivotide tetraxetan was initially approved in March 2022 in the metastatic castration-resistant setting for patients who had received prior treatment with an ARPI and taxane-based chemotherapy. In March 2025, the FDA granted approval to an expanded indication for the agent, allowing the radioligand therapy to be used in the pre-chemotherapy setting.²

The recent approval was supported by data from the phase 3 PSMAfore trial (NCT04689828), which showed that lutetium (177Lu) vipivotide tetraxetan prolonged rPFS compared with a change in ARPI in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had progressed on a previous ARPI.

"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, MD, President, Development and Chief Medical Officer at Novartis, in the news release from the company.¹ "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."

Novartis stated that they plan to file for regulatory approval of lutetium (177Lu) vipivotide tetraxetan in the mHSPC setting in the second half of 2025, pending FDA feedback. Data from the PSMAddition study will also be shared at an upcoming medical meeting, the company reported.

About PSMAddition

In total, the international, open-label, prospective PSMAddition study enrolled approximately adult 1144 patients who were randomly assigned 1:1 to receive lutetium (177Lu) vipivotide tetraxetan plus SOC vs SOC alone.³ Patients in the control arm were allowed to crossover to the treatment arm after confirmation of rPFS per blinded independent review committee (BICR) and per the discretion of the treating physician.

To be eligible for enrollment, patients needed to have an ECOG performance score of 0 to 2, a life expectancy greater than 9 months, adequate organ function, and an albumin level of at least 2.5 g/dL.

The primary end point for the trial was rPFS, with OS as a key secondary end point. The trial is also assessing PSA90 responses, the time to mCRPC, progression-free survival, overall response rate, disease control rate, and duration of response, among other measures.

Lutetium (177Lu) vipivotide tetraxetan is also currently being assessed in the oligometastatic setting in the phase 3 PSMA-DC trial (NCT05939414).

REFERENCES
1. Novartis Pluvicto demonstrates statistically significant and clinically meaningful rPFS benefit in patients with PSMA-positive metastatic hormone-sensitive prostate cancer. News release. Novartis. Published online and accessed June 2, 2025. https://www.novartis.com/us-en/news/media-releases/novartis-pluvicto-demonstrates-statistically-significant-and-clinically-meaningful-rpfs-benefit-patients-psma-positive-metastatic-hormone-sensitive-prostate-cancer

2. FDA approves Novartis radioligand therapy Pluvicto for earlier use before chemotherapy in PSMA-positive metastatic castration-resistant prostate cancer. News release. Novartis Pharma AG. March 28, 2025. Accessed June 2, 2025. https://www.novartis.com/news/media-releases/fda-approves-novartis-radioligand-therapy-pluvicto-earlier-use-chemotherapy-psma-positive-metastatic-castration-resistant-prostate-cancer

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. Last updated March 5, 2025. Accessed June 2, 2025. https://clinicaltrials.gov/study/NCT04720157