Novartis Announces Positive Phase III VISION Trial Results for 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer

June 05, 2021 /BioValleyBIOON/ --Novartis(Novartis) recently announced the initial results from the Phase 3 VISION study evaluating the targeted radioligand therapy 177Lu-PSMA-617 for the treatment of PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). This international, prospective, randomized, open-label, multicenter study assessed the efficacy and safety of 177Lu-PSMA-617 in combination with best standard of care (SOC) compared with SOC alone. The results showed that,Compared with SOC, 177Lu-PSMA-617 in combination with SOC significantly prolonged overall survival (OS) and radiographic progression-free survival (rPFS).

177Lu-PSMA-617 is a radioligand therapy., this class of therapy combines a targeted compound that binds to tumor-expressed markers with a radioisotope, inducing DNA damage and inhibiting tumor growth and replication. This treatment modality can precisely deliver to# TumorDelivers radiation in a cell-targeted manner while limiting damage to surrounding normal tissues.

The prognosis for metastatic prostate cancer is poor, with a 5-year survival rate of only 30%. The aforementioned phase 3 data, the first for a radioligand therapy in advanced prostate cancer, confirm the potential of 177Lu-PSMA-617 to improve clinical outcomes. Based on these study results,NovartisMarketing authorization applications for 177Lu-PSMA-617 are planned for submission in the United States and the European Union in the second half of 2021. The company also plans to initiate two pivotal trials for the treatment of early metastatic prostate cancer in the second half of this year, with the aim of advancing into earlier disease stages.

Prostate cancer (Image source: hopkinsmedicine.org)

The VISION trial enrolled a total of 831 patients with PSMA-PET–positive metastatic castration-resistant prostate cancer (mCRPC) who had disease progression following prior treatment with taxanes and androgen receptor-directed therapy (ARDT). In the study, these patients were randomized in a 2:1 ratio to the experimental and control groups. The experimental group (n=551) received 177Lu-PSMA-617 (7.4 GBq administered via intravenous infusion every 6 weeks for up to 6 cycles) plus standard of care (SOC), while the control group (n=280) received SOC alone. The primary endpoints of the trial were radiographic progression-free survival (rPFS) and overall survival (OS).

The results showed that the study met its two primary endpoints: compared with SOC, 177Lu-PSMA-617 in combination with SOC significantly prolonged OS and rPFS in patients with PSMA-positive mCRPC. The specific efficacy data were as follows: (1)Regarding OS, compared with the SOC group, the 177Lu-PSMA-617 + SOC group demonstrated significant improvement in OS (median OS: 15.3 months vs. 11.3 months), with a statistically significant between-group OS difference of 4 months (one-sided p < 0.001) and a 38% reduction in the risk of death.（HR=0.62；95%CI:0.52-0.74）；（2）Regarding rPFS, compared with the SOC group, the 177Lu-PSMA-617 + SOC group demonstrated a significant improvement in rPFS (median rPFS: 8.7 months vs. 3.4 months); the between-group difference in OS (5.3 months) was statistically significant (one-sided p < 0.001), representing a 60% reduction in the risk of radiographic progression or death.（HR=0.40；99.2%CI:0.29-0.57）。

The study also met its key secondary endpoints: (1) significantly delayed the time to the first symptomatic skeletal event, with a median time of 11.5 months (95% CI: 10.3, 13.2) in the 177Lu-PSMA-617 + SOC group compared with 6.8 months (95% CI: 5.2, 8.5) in the SOC group (HR = 0.50; 95% CI: 0.40–0.62; two-sided p < 0.001); (2) significantly improved the overall response rate (ORR), with significant differences observed in patients with measurable or non-measurable disease at baseline (partial or complete response rate of 29.8% in the 177Lu-PSMA-617 + SOC group vs. partial response rate of 1.7% in the SOC group; two-sided p < 0.001); and (3) significantly improved the disease control rate (DCR), which was 89.0% in the 177Lu-PSMA-617 + SOC group compared with 66.7% in the SOC group (two-sided p < 0.001).

Regarding safety, the incidence of treatment-emergent adverse events (TEAEs) reported in the 177Lu-PSMA-617 + SOC group was higher than that in the SOC group (85.3% vs. 28.8%). With respect to TEAE-related discontinuation rates, 11.9% of patients in the 177Lu-PSMA-617 + SOC group discontinued 177Lu-PSMA-617 and 8.5% discontinued SOC, whereas 7.8% of patients in the SOC group discontinued treatment.

177Lu-PSMA-617 (Image source: embs.org)

Prostate cancer is a cancer that occurs in the prostate, a small walnut-shaped gland located in the male pelvis. In castration-resistant prostate cancer (CRPC), despite the use of hormone therapy to lower testosterone levels, the tumor still shows signs of growth, such as elevated prostate-specific antigen (PSA) levels. In metastatic CRPC (mCRPC),TumorIt has metastasized to other parts of the body, such as adjacent organs or bones, and remains refractory to hormone therapy. The 5-year survival rate for patients with mCRPC is approximately 15%.

Despite advances in the treatment of prostate cancer, there remains a very high unmet medical need for novel targeted treatment options for patients with mCRPC. More than 80% of prostate cancer`Tumor`highly expresses a phenotypic biomarker known as prostate-specific membrane antigen (PSMA), making it a promising# DiagnosisTarget (imaged via positron emission tomography [PET]) and therapeutic target for radioligand therapy.

177Lu-PSMA-617 is a PSMA-targeted radioligand therapy developed for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This drug is a precision cancer treatment that combines a targeting compound (ligand) with a therapeutic radioisotope (radiation particle). After injection into the bloodstream, 177Lu-PSMA-617 binds to prostate cancer cells expressing PSMA (a transmembrane protein), resulting in a higher uptake of the drug by tumors compared to normal tissues. Once bound, the radiation (β particles) from the radioisotope will damageTumorcells, destroying their replication capacity and/or inducing cell death. The radiation emitted by radioisotopes acts only over a very short range to limit damage to surrounding cells. (Bioon.com)

Original source: Novartis 177Lu-PSMA-617 significantly improves overall survival and radiographic progression-free survival for men with metastatic castration-resistant prostate cancer in Phase III VISION study