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Breaking News: First-in-Class Radioligand Therapy Approved for Advanced Prostate Cancer

What this means for patients: Today, a new treatment known as 177lutetium-PSMA-617 (Lu-PSMA; trade name Pluvicto®) was approved by the FDA for certain patients with advanced prostate cancer. This medicine delivers a small dose of radiation attached to a molecule that specifically binds to prostate cancer cells. It has been shown to help patients with advanced prostate cancer live longer and maintain quality of life.

177Lutetium-PSMA-617 (Lu-PSMA) is now FDA-approved for patients with metastatic castration-resistant prostate cancer who have received certain other treatments (androgen receptor pathway targeting agents and taxane-based chemotherapy). Patients must also have a positive PSMA PET scan. This represents a paradigm shift in the treatment of advanced prostate cancer, and is hopeful news for patients who have seen their disease progress on other therapies.

Lu-PSMA works to deliver a small amount of radiation to prostate cancer cells anywhere in the body. One part of the Lu-PSMA molecule recognizes and binds to its target, called PSMA (prostate-specific membrane antigen). PSMA is a protein that is present on nearly all prostate cancer cells but not on most normal tissue. This PSMA-seeking “arrow” is chemically linked to a radioactive “payload” called lutetium-177. When Lu-PSMA binds to the prostate cancer cell, the cell takes up that radioactive drug and is killed. The radiation from lutetium-177 travels only a short distance outside the target cell, so the surrounding normal tissue is largely spared.

According to Novartis, the manufacturer, this new therapy is expected to be available to physicians and patients within weeks.

Approval was based on the large, randomized international Phase 3 VISION trial, led by PCF-funded investigators Dr. Michael Morris (Memorial Sloan Kettering Cancer Center) and Dr. Oliver Sartor (Tulane University). This study showed that Lu-PSMA prolongs life, reduces disease progression, and maintains quality of life. Overall, patients treated with Lu-PSMA plus standard of care lived 4 months longer on average vs. patients treated with standard of care alone. The time to seeing worsening disease on scans was also longer by an average of more than 5 months. While the treatment is well-tolerated, side effects such as dry mouth and nausea were more common in the Lu-PSMA arm.

With this approval, PSMA-targeted therapy becomes the newest class of treatment for prostate cancer. Studies are underway to test the effectiveness of Lu-PSMA at earlier stages of prostate cancer, and in combination with other treatments such as immunotherapy.

Lu-PSMA is approved for use in “PSMA Positive” tumors – thus making it a form of precision medicine. This means that the tumor cells have the PSMA protein on their surface, and the Lu-PSMA molecule will be able to bind to them to deliver the radiation. Unlike other types of precision medicines (such as immunotherapy), which require a tumor test, in this case we can determine PSMA “positivity” with a PET scan of the whole body. The first PSMA PET scan was approved in 2020.

Currently, there are two different types of FDA-approved PSMA PET imaging agents. One type uses gallium-68-PSMA-11 (Locametz® and Illuccix®), and a second type is called piflufolastat F 18 (PYLARIFY®). Under this FDA approval, patients must have a positive scan with an approved gallium-68-PSMA-11 agent to be selected for treatment with Lu-PSMA. If you are considering a PSMA PET scan, please discuss with your doctor which type of imaging agent might be recommended for you.

PCF has invested over $28 million in research on PSMA since inception in 1993. Dr. Neil Bander, now the Bernard and Josephine Chaus Professor of Urological Oncology at Weill Cornell Medicine, first created an antibody to PSMA that launched the field and helped scientists understand the distribution of PSMA in prostate cancer patients. Read more about PCF’s role in the development of PSMA imaging and therapeutics here.

PCF congratulates the VISION trial investigators and all those who came before them to contribute to this approval. These major developments in patient care required years of innovation and careful, deliberate work behind the scenes in laboratory studies and early-phase trials.