Novartis reports new Pluvicto data in metastatic hormone-sensitive prostate cancer

Novartis reported new data from the Phase III PSMAddition trial showing improved prostate-specific antigen responses with Pluvicto combined with standard of care in PSMA-positive metastatic hormone-sensitive prostate cancer. The risk of PSA progression was 58% lower in patients treated with Pluvicto plus standard of care compared with standard of care alone, and Novartis has filed regulatory submissions in the United States, China and Japan, with decisions expected in the second half of 2026.

The new results come from the PSMAddition trial, first reported at last year's ESMO cancer congress, which formed the basis of filings to extend the label of Pluvicto from its current use in castration-resistant prostate cancer. PSMAddition is a Phase III, open-label, prospective, 1:1 randomised study comparing the efficacy and safety of Pluvicto in combination with standard of care, androgen receptor pathway inhibitor plus androgen deprivation therapy, versus standard of care alone in adult patients with PSMA-positive metastatic hormone-sensitive prostate cancer.

Results demonstrated that patients treated with Pluvicto experienced a higher frequency and greater depth of PSA response when combined with standard of care than with standard of care alone. More than 98% of patients in both arms had substantial declines in PSA levels, but more in the Pluvicto group achieved a deep PSA reduction, reaching levels below 0.2 ng/mL. Deep PSA reduction was higher in patients receiving the Pluvicto combination at 12, 24 and 48 weeks, with 87.43% of Pluvicto-treated patients reaching this target at 48 weeks compared to 74.9% of the control group.

At ESMO, Novartis reported that the Pluvicto regimen reduced the risk of disease progression or death, radiographic progression-free survival, by 28% compared to the control group. The primary endpoint is radiographic progression-free survival, defined as the time to radiographic progression or death. The key secondary endpoint for overall survival is time to death from any cause.

The study remains ongoing, and a total of 1,144 patients with metastatic hormone-sensitive prostate cancer across 20 countries have been randomised in the trial. According to the company, the safety profile and tolerability of Pluvicto were consistent with those observed in the Phase 3 trials PSMAfore and VISION. Grade 3 or higher adverse events were reported in 50.7% of patients in the Pluvicto plus standard-of-care arm, compared with 43% in the standard-of-care-alone arm.

Pluvicto is currently approved for PSMA-positive metastatic castration-resistant prostate cancer and is under investigation for metastatic hormone-sensitive prostate cancer. The therapy was first approved for progressive, PSMA-positive metastatic castration-resistant prostate cancer in 2022 after initial chemotherapy and had its label extended last year to include the pre-chemotherapy setting based on the PSMAfore trial results.