Novartis reported new Phase 3 PSMAddition data showing that Pluvicto (lutetium (177Lu) vipivotide tetraxetan) plus standard of care (androgen receptor pathway inhibitor [ARPI] plus androgen deprivation therapy [ADT]) reduced the risk of prostate-specific antigen (PSA) progression in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC) compared with standard of care alone. In the study, the risk of PSA progression was 58% lower with Pluvicto plus standard of care than with standard of care alone (hazard ratio 0.42; 95% CI: 0.30–0.59).
The company said patients treated with Pluvicto experienced a higher frequency and greater depth of PSA response when combined with standard of care versus standard of care alone. Nearly all patients in both arms (more than 98%) had substantial PSA declines, but a higher proportion of those receiving the Pluvicto combination achieved a deep PSA reduction, defined as a PSA nadir below 0.2 ng/mL.
Deep PSA responses favored the Pluvicto arm across multiple time points. At week 12, 47.6% (235/494) of patients on Pluvicto plus ARPI and ADT reached a PSA below 0.2 ng/mL, compared with 37.7% (169/448) on ARPI plus ADT alone. By week 24, rates were 73.7% (334/453) versus 59.7% (250/419), and by week 48 they were 87.4% (320/366) versus 74.9% (295/394), respectively.
“Our goal in hormone-sensitive prostate cancer is to attack and delay the cancer before it develops resistance,” said Fred Saad, Professor and Chairman, Department of Surgery, University of Montreal. He noted that the PSA responses seen with 177Lu-PSMA-617 in combination with current standard of care, together with previously reported radiographic progression-free survival data, suggest that treatment intensification with radioligand therapy may help delay disease progression.
The safety profile and tolerability of Pluvicto in PSMAddition were described as consistent with prior PSMAfore and VISION experience. Grade 3 or higher adverse events occurred in 50.7% of patients receiving Pluvicto plus standard of care and 43% of those on standard of care alone. The most common adverse events of any grade included dry mouth, fatigue, nausea, hot flush and anemia.
“These data show that combining Pluvicto with today’s standard of care resulted in deeper PSA responses than ADT plus ARPI alone,” said Mark Rutstein, M.D., Global Head, Oncology Development at Novartis. He said the findings align with a move toward more precision-based approaches and earlier treatment intensification in mHSPC. Novartis has submitted supplemental new drug applications in the United States, China and Japan, with initial regulatory decisions expected in the second half of 2026.
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