Phase 3 Trial of 177Lu-PSMA-617 Meets Survival End Points

Novartis announced that its investigational targeted radioligand therapy 177Lu-PSMA-617 demonstrated statistically significant improvements in overall and radiographic progression-free survival versus standard-of-care therapy in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer.

Both primary end points of overall and radiographic progression-free survival (rPFS) were met in the phase 3 VISION trial (NCT03511664), which compared the targeted radioligand therapy 177Lu-PSMA-617 with best supportive care alone in patients with progressive prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC), reported Novartis who is responsible for developing the therapy.1

The investigational agent is a precision cancer therapy that combines a targeting compound, or ligand, with a therapeutic radioisotope that binds with prostate cancer cells that express PSMA.

“Patients with metastatic castration-resistant prostate cancer have a less than 1 in 6 chance of surviving 5 years and need new treatment options. These groundbreaking data confirm our belief in the potential of 177Lu-PSMA-617 to reimagine outcomes for these patients through phenotypic precision medicine. We intend to submit these data to regulatory authorities as soon as possible,” John Tsai, MD, Head of Global Drug Development and Chief Medical Officer for Novartis, said in a press release. “We would like to thank the patients who volunteered to participate in this study as well as the clinical teams at each of the trial sites. We would not be able to realize our commitment to reimagining medicine without the partnership of patients and their families.”

The VISION trial is currently ongoing but is closed to enrollment, with an estimated 750 patients already randomized in a 2:1 fashion to the treatment arms. The study is open-label, with patients receiving disease monitoring for 6 to 10 months of the treatment period. Best supportive care was defined as physician’s choice of therapy, with the exception of investigational agents, cytotoxic chemotherapy, other systemic radioisotopes, and hemi-body radiotherapy. Long-term follow-up of the study will include collection of survival data and treatment updates, adverse event monitoring, and blood chemistries.

Patients who are eligible for the trial have an ECOG performance status of 2 or less, a life expectancy of greater than 6 months, a positive 68Ga-PSMA-11 PET/CT scan, a castrate level or serum/plasma testosterone of lower than 50 ng/dL or 1.7 nmol/L, and prior history with at least 1 novel androgen axis drugs.

The company expects results of the trial to be ready for presentation at an upcoming medical meeting as well as regulatory submission in the United States and European Union.

Antitumor activity and safety of 177Lu-PSMA-617 have been established previously in a phase 2 trial whose results were published in The Lancet Oncology.2 The single-arm, single-center study recruited patients with metastatic castration-resistant prostate cancer who had progressive disease following standard therapy, which included taxane-based chemotherapy and second-generation androgen antagonists. The main efficacy outcomes were toxicity and prostate-specific antigen response according to Prostate Cancer Clinical Trial Working Group criteria, with greater than 50% decline from baseline.

In total, 57% patients (n = 30) achieved a PSA response. There were no treatment-related deaths, and 177Lu-PSMA-617 administration was well tolerated. The most common treatment-related adverse event was dry mouth, occurring in 87% of patients, which was mostly comprised of grade 1 events. Grade 3/4 thrombocytopenia occurred in 8 patients, but only 4 were considered to be treatment related. Additionally, the investigators concluded that treatment results in improved quality of life due to a reduction in pain in this patient population.


1. Novartis announces positive result of phase III study with radioligand therapy 177Lu-PSMA-617 in patients with advanced prostate cancer. News release. Novartis. March 23, 2021. Accessed March 23, 2021.

2. Hofman MS, Violet J, Hicks RJ, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19(6):825-833. doi: 10.1016/S1470-2045(18)30198-0