Pluvicto shows statistically significant and clinically meaningful radiographic progression-free survival benefit in patients with PSMA–positive metastatic castration-resistant prostate cancer
Novartis has announced the pivotal Phase III PSMAfore study with Pluvicto(INN: lutetium (177Lu) vipivotide tetraxetan), a prostate-specific membrane antigen (PSMA)-targeted radioligand therapy, met its primary endpoint
Pluvicto 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 (ARPI) therapy, compared to a change in ARPI. No unexpected safety findings were observed in PSMAfore; data are consistent with the already-well established safety profile of Pluvicto.
This is the second positive read-out for Pluvicto in a Phase III trial following the VISION study, where patients with PSMA–positive mCRPC who received Pluvicto plus standard of care after being treated with ARPI and taxane-based chemotherapy had a statistically significant reduction in risk of death. The PSMAfore results continue to support the important role of Pluvicto in treating patients with prostate cancer. The Phase III data will be presented at an upcoming medical meeting and discussed with the FDA in 2023 for regulatory approval.
The vast majority of patients diagnosed with CRPC already present with metastases at time of diagnosis, patients with metastatic prostate cancer have an approximate 3 in 10 chance of surviving 5 years. Despite recent advances, outcomes for those who progress after standard of care second-generation ARPI remain poor, and there is an urgent need for new targeted treatment options to help improve long-term outcomes. Pluvicto is already approved for treatment in adult patients with PSMA–positive mCRPC who have been treated with ARPI and taxane-based chemotherapy in the United States and several other countries.
About the PSMAfore Study; PSMAfore is a Phase III, open-label, multi-center, 1:1 randomized study comparing the efficacy and safety of Pluvicto to a change in ARPI in patients with PSMA–positive mCRPC. Patients enrolled must have progressed only once after receiving a second-generation ARPI. There were 469 participants enrolled in the study. The primary endpoint is rPFS, defined as the time from randomization to radiographic progression by PCWG3-modified RECIST v1.1 (as assessed by blinded independent central review) or death.Evaluation of overall survival, the key secondary endpoint, is ongoing as data remain immature.
About Pluvicto (lutetium (177Lu) vipivotide tetraxetan): Pluvicto is an intravenous radioligand therapy combining a targeting compound (a ligand) with a therapeutic radionuclide (a radioactive particle, in this case lutetium-177). After administration into the bloodstream, Pluvicto 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.
Pluvicto is approved in the US and other countries to treat adults with a type of advanced cancer called PSMA–positive mCRPC and who have already been treated with other anticancer treatments (ARPI and taxane-based chemotherapy). More specifically, in March 2022, the FDA approved Pluvicto. In August and September 2022, the Medicines and Healthcare products Regulatory Agency (MHRA) and Health Canada approved Pluvicto in Great Britain and Canada, respectively. In October 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion recommending the granting of a marketing authorization for Pluvicto. These regulatory decisions are supported by the results from the pivotal Phase III VISION study, where patients with pre-treated PSMA–positive mCRPC who received Pluvicto plus standard of care had a statistically significant reduction in the risk of death; both alternate primary endpoints of radiographic progression free survival and overall survival were met.
About Phenotypic Precision Medicine in Advanced Prostate Cancer: Despite advances in prostate cancer care, there is a high unmet need for new targeted treatment options to improve outcomes for patients with mCRPC. More than 80% of patients with prostate cancer highly express a phenotypic biomarker called prostate specific membrane antigen (PSMA), making it a promising diagnostic (through positron emission tomography (PET) scan imaging) and therapeutic target for radioligand therapy. This differs from ‘genotypic’ precision medicine which targets specific genetic alterations in cancer cells.
Novartis is also evaluating opportunities to investigate Pluvicto radioligand therapy in earlier stages of prostate cancer.