On December 5, Novartis announced the pivotal phase III PSMAfore study of lutetium (Lu-177) vipivotide tetraxetan, a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy, met its primary endpoint. The therapy demonstrated a statistically significant and clinically meaningful improvement in radiographic progression-free survival (RPFS) in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) after treatment with androgen-receptor pathway inhibitor therapy, compared to a change in androgen-receptor pathway inhibitors.
No unexpected safety findings were observed in PSMAfore. Data are consistent with the already-well established safety profile of Lu-177 vipivotide tetraxetan.
This is the second positive phase III trial of Lu-177 vipivotide tetraxetan following the VISION study, where patients with PSMA-positive mCRPC who received the therapy plus standard of care after being treated with an androgen-receptor pathway inhibitor and taxane-based chemotherapy had a statistically significant reduction in risk of death. The new data will be presented at an upcoming medical meeting and discussed with the U.S. Food and Drug Administration (FDA) in 2023 for regulatory approval.
“With the announcement of these positive topline phase III results, [Lu-177 vipivotide tetraxetan] becomes the first PSMA-targeted radioligand therapy to demonstrate significant and clinically meaningful benefits for people living with this type of prostate cancer who have not received taxane-based chemotherapy,” said Shreeram Aradhye, MD, President of Global Drug Development and Chief Medical Officer at Novartis. “We look forward to discussing the data with health-care authorities in order to bring this innovative new early treatment option to many more [patients with] prostate cancer sooner after their diagnosis.”
The vast majority of patients diagnosed with castration-resistant prostate cancer already present with metastases at time of diagnosis, and patients with metastatic prostate cancer have an approximate 3 in 10 chance of surviving for 5 years. Despite recent advances, outcomes for those whose disease progresses after standard-of-care second-generation androgen-receptor pathway inhibitors remain poor, and there is an urgent need for new targeted treatment options to help improve long-term outcomes.
About the PSMAfore Study
PSMAfore is a phase III, open-label, multicenter, 1:1 randomized study comparing the efficacy and safety of Lu-177 vipivotide tetraxetan to a change in androgen-receptor pathway inhibitors in patients with PSMA-positive mCRPC. Patients enrolled in the study must have had disease progression only once after receiving a second-generation androgen-receptor pathway inhibitor. There were 469 participants enrolled in the study.
The primary endpoint is RPFS, defined as the time from random assignment to radiographic progression by Prostate Cancer Working Group 3–modified Response Evaluation Criteria in Solid Tumors version 1.1 (as assessed by blinded independent central review) or death. Evaluation of overall survival, the key secondary endpoint, is ongoing as data remain immature.
About Lu-177 Vipivotide Tetraxetan
Lu-177 vipivotide tetraxetan is an intravenous radioligand therapy combining a targeting compound (a ligand) with a therapeutic radionuclide (a radioactive particle). After administration into the bloodstream, Lu-177 vipivotide tetraxetan binds to target cells, including prostate cancer cells that express PSMA, a transmembrane protein. Once bound, energy emissions from the radioisotope damage the target cells and nearby cells, disrupting their ability to replicate and/or triggering cell death.
The therapy is approved in the United States and other countries to treat adults with PSMA-positive mCRPC and who have already been treated with other anticancer treatments (androgen-receptor pathway inhibitor and taxane-based chemotherapy). More specifically, in March 2022, the FDA approved Lu-177 vipivotide tetraxetan. In August and September 2022, the Medicines and Healthcare Products Regulatory Agency and Health Canada approved Lu-177 vipivotide tetraxetan in Great Britain and Canada, respectively. In October 2022, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion recommending the granting of a marketing authorization for Lu-177 vipivotide tetraxetan.
These regulatory decisions are supported by the results from the pivotal phase III VISION study, in which patients with pretreated PSMA-positive mCRPC who received Lu-177 vipivotide tetraxetan plus standard of care had a statistically significant reduction in the risk of death; both alternate primary endpoints of RPFS and overall survival were met.
Novartis is also evaluating opportunities to investigate Lu-177 vipivotide tetraxetan radioligand therapy in earlier stages of prostate cancer.
