FDA Grants Priority Review to 177Lu-PSMA-617 in mCRPC

Positive findings from the phase 3 VISION have led the FDA to grant priority review to 177Lu-PSMA-617 for patients with metastatic castration-resistant prostate cancer.

The FDA has accepted the new drug application for 177Lu-PSMA-617 and granted it prior review for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in the post androgen receptor pathway inhibition, post-taxane-based chemotherapy setting, according to a press release issued by Novartis.1

Consideration of the NDA for 177Lu-PSMA-617 is based on results from the phase 3 VISION study in which the agent combined with standard of care therapy demonstrated significant improvement in overall survival as well as radiographic progression-free survival compared with SOC alone in patients with prostate-specific maturation antigen (PSMA)-positive mCRPC. The results from this study previously led the FDA to grant breakthrough therapy designation to 177Lu-PSMA-617 in July 2021.

A decision on whether to approve 177Lu-PSMA-617 for this indication will be made by the FDA in the first half of 2022.

As a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and encompasses the microenvironment, investigators led by Oliver Sartor, MD of Tulane School of Medicine, sought to show that 177Lu-PSMA-617 could improve outcomes with SOC in patients with PSMA-positive mCRPC. The VISION was international and open-label and randomized patients 2:1 to received either 177Lu-PSMA-617 at 7.4 GBq (+/- 10%) intravenously every 6 weeks for up to 6 cycles with SOC or the best SOC alone. A total of 831 patients were included and assessed for the coprimary end points of OS and rPFS. The secondary end pointsof the study included the number of patients with treatment-emergent adverse events (TEAEs).2

At a median follow-up of 20.9 months, the median OS observed with 177Lu-PSMA-617 plus SOC was 15.3 months compared with 11.3 months in the SOC-alone arm (HR, 0.61; 95% CI, 0.52-0.74; P <.0001). In terms of rPFS, the median observed with 177Lu-PSMA-617 plus SOC was 8.7 months versus 3.4 months with SOC alone (HR, 0.40; 99.2% CI, 0.29-0.57; P <.001). Moreover, findings for all the secondary efficacy end points favored the 177Lu-PSMA-617 combination.

The safety of 177Lu-PSMA-617 in the VISION study was consistent with its profile in earlier studies, according to the VISON investigators. Patients were exposed to the drug for a median of 6.9 months (range, 0.3-10.2). Any-grade AEs were observed in 98.1% of patients in the combination arm compared with 82.9% in the SOC arm. The most common AEs observed with the experimental combination were fatigue (43.1%), dry mouth (38.8%), and nausea (35.3%). Fatigue and nausea were also common in the SOC arm at 22.9% and 16.6%, respectively.

“Treatment with 177Lu-PSMA-617 was associated with toxic effects that were mainly of grade 3 or lower, and this therapy also extended the time to symptomatic skeletal events, prolonged the time to worsening of health-related quality of life and pain, and delayed biochemical progression,” wrote the Sartor et al.

Further exploration of 177Lu-PSMA-617’s ability to improve outcomes in patients with prostate cancer is currently underway in 2 investigational trials, in which the drug is brought into earlier lines of therapy (NCT04689828, NCT04720157). These studies respectively evaluate 177Lu-PSMA-617 in the pre-taxane setting and the metastatic hormone-sensitive setting.


1. FDA grants priority review for investigational targeted radioligand therapy 177Lu-PSMA-617 for patients with metastatic castration-resistant prostate cancer (mCRPC). News release. September 28, 2021. Accessed September 28, 2021. https://bit.ly/2Y5Omez

2. Sartor O, de Bono J, Chi Km, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021; 385(12):1091-1103. doi: 10.1056/NEJMoa2107322