The data from the Phase III PSMAfore trial was presented at the 2023 European Society for Medical Oncology (ESMO) Congress. Data presented at the Presidential Symposium showed that lutetium (177Lu) vipivotide tetraxetan met its primary endpoint with a clinically meaningful and statistically significant benefit in radiographic progression-free survival (rPFS) in patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) after treatment with androgen receptor pathway inhibitor (ARPI) therapy, compared to a change in ARPI.

“The rPFS data are impressive and the treatment effect is comparable with what was observed in the VISION trial,” said Dr. Oliver Sartor, PSMAfore Co-Principal Investigator, Chairman of the Trial Steering Committee and adjunct professor in the Department of Urology at Tulane University School of Medicine, New Orleans, LA, one of the many sites where the trial was conducted. “We look forward to a future where lutetium (177Lu) vipivotide tetraxetan may be a viable therapy for patients in need of alternative, earlier options.”

“These promising results from PSMAfore could change the treatment paradigm for advanced prostate cancer by allowing patients to potentially avoid or delay taxane-based chemotherapy, which carries a heavy burden of side effects,” said Jeff Legos, Executive Vice President, Global Head of Oncology Development at Novartis. “While data collection for overall survival continues, the consistency of the benefit observed on other clinically meaningful efficacy endpoints, together with improved quality of life and favourable safety profile, show the potential of lutetium (177Lu) vipivotide tetraxetan for taxane-naïve patients with mCRPC.”

The trial met its primary endpoint of rPFS2 with a 59% reduction in the risk of radiographic disease progression in patients with lutetium (177Lu) vipivotide tetraxetan versus a change of ARPI. Using a data cut-off with a median of 8.6 months longer study follow-up, an updated rPFS analysis (HR 0.43; 95% CI: 0.33, 0.54) demonstrated a consistent clinical benefit in patients with lutetium (177Lu) vipivotide tetraxetan versus a change in ARPI, more than doubling time to radiographic disease progression (12.0 months vs. 5.6 median months).

Patients on lutetium (177Lu) vipivotide tetraxetan also showed improved quality of life, maintaining their FACT-P total score for 3 months longer than a change in ARPI (7.5 vs. 4.3 months), with a delay in worsening pain (BPI-SF) of 5.0 versus 3.7 months1. Other clinically meaningful efficacy endpoints also favoured lutetium (177Lu) vipivotide tetraxetan, with a PSA decline of at least 50% being >2.5X more frequent with lutetium (177Lu) vipivotide tetraxetan than with a change in ARPI. 

At the second interim OS analysis with 45% of events, the pre-specified crossover-adjusted OS analysis demonstrated a hazard ratio of 0.80 (95% CI: 0.48, 1.33)1. The unadjusted intent-to-treat OS analysis was confounded as 84% of patients who discontinued ARPI due to radiographic progression crossed over to receive lutetium (177Lu) vipivotide tetraxetan. The trial will continue to assess OS, with the next interim OS analysis expected in 2024. 

The trial demonstrated a favourable safety profile with 6 cycles of lutetium (177Lu) vipivotide tetraxetan.

The most frequently reported all-grade AEs for lutetium (177Lu) vipivotide tetraxetan were primarily Grade 1–2 and included dry mouth (57.3%), asthenia (31.7%), nausea (31.3%), anaemia (24.2%) and fatigue (22.9%).

Currently, patients diagnosed with metastatic prostate cancer have a 5-year survival rate of approximately 30%3 and there remains an urgent need for treatment options for patients who have disease progression despite the current standard of care.

Source: Novartis