Phase III VISION Study Reports Significant Improvement in Overall Survival and Progression-free Survival with Novartis 177Lu-PSM

Men with castration-resistant prostate cancer (mCRPC) who received Novartis 177Lu-PSMA-617 plus best standard of care (SOC) had a 38% reduction in risk of death (median overall survival [OS] benefit of 4 months) and a 60% reduction in the risk of radiographic disease progression or death (median rPFS benefit of 5 months) compared to best SOC alone, according to results of the Phase III VISION study evaluating 177Lu- PSMA-617, a targeted radioligand therapy.

The difference in OS between study arms was statistically significant (one-sided p<0.001), with an estimated 38% reduction in risk of death in the 177Lu-PSMA-617 arm (n=551) compared to the best SOC only arm (n=280) (hazard ratio: 0.62 with 95% confidence interval (CI): (0.52, 0.74))1. These results will be presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting plenary session on June 6.

Patients receiving 177Lu-PSMA-617 also demonstrated a statistically significant (one-sided p<0.001) 60% risk reduction for radiographic progression-free survival or death (rPFS), compared to the best SOC only arm (hazard ratio: 0.40 with 99.2% CI: (0.29 0.57)).¹ There was a higher rate of drug-related treatment emergent adverse events reported in the 177Lu-PSMA-617 treatment arm (85.3%) compared to SOC alone (28.8%).¹

Across both arms of the study, rates of treatment discontinuation associated with treatment-emergent adverse events occurred as follows: In the 177Lu- PSMA-617 plus SOC arm, 11.9% of patients discontinued 177Lu-PSMA-617 and 8.5% discontinued SOC; while in the SOC alone arm 7.8% of patients discontinued treatment.¹

"Patients suffering from metastatic CRPC who have progressed through contemporary hormonal treatments and chemotherapy have few meaningful therapeutic options," said Michael J. Morris, MD, who chaired the study's Scientific Committee and is the Prostate Cancer Section Head, Genitourinary Oncology Service, Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center. "The study demonstrated that 177Lu-PSMA-617 improves disease progression and prolongs survival, which are key measures of clinical benefit in the mCRPC population. I am grateful to be a part of this study that may lead to additional therapeutic options for these patients."

"Men with metastatic prostate cancer have an approximately 3 in 10 chance of surviving 5 years2. These data from the first Phase III study of a radioligand therapy in this advanced prostate cancer setting confirm the potential of 177Lu-PSMA-617 targeted therapy to improve clinical outcomes," said John Tsai, Head of Global Drug Development and Chief Medical Officer for Novartis. "Our comprehensive development program for this targeted therapy seeks to reach eligible patients with advanced prostate cancer, who express the PSMA biomarker1,3-6. And, we won't stop with prostate cancer, our team is exploring next generation RLT across a number of tumor types."

Two additional studies with 177Lu-PSMA-617 radioligand therapy in earlier lines of treatment for metastatic prostate cancer are planned to start in the first half of 2021, investigating potential clinical utility in the mCRPC pre- taxane setting (PSMAfore) and in the metastatic hormone-sensitive setting (PSMAddition).