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There is incredibly hopeful news on the horizon for men with metastatic castration-resistant prostate cancer (mCRPC). Today, promising results were released from a clinical trial of a revolutionary new class of therapy for mCRPC: a radioactive molecule called ¹⁷⁷Lu-PSMA-617 that hunts down and kills prostate cancer cells wherever they are in the body. More information will be presented during the online 2021 American Society of Clinical Oncology (ASCO) Annual Meeting this weekend.

Why is this so important for patients? Metastatic prostate cancer may initially respond to hormone therapy and other medications. But over time, the cancer often “outsmarts” the drugs, developing adaptations that allow it to thrive even in a low-testosterone environment, and it begins to grow. More options are urgently needed. In the trial, this treatment actually helped patients with mCRPC live longer. Having funded research into this approach for more than 25 years, PCF is incredibly gratified to see those years of hard work come to fruition for patients.

¹⁷⁷Lu-PSMA-617 (Lu-PSMA) is a molecule with 2 main parts. PSMA, short for Prostate Specific Membrane Antigen, is a protein that is found on the surface of prostate cancer cells. Lu-PSMA is composed of a small chemical that binds to PSMA (the “PSMA-617” part of the name), honing in on prostate cancer cells. Attached to this binding chemical is a radioactive “payload,” in this case the isotope lutetium-177 (¹⁷⁷Lu). When the chemical binds to prostate cancer cells, the radioactive molecule is taken in, delivering a high dose of radiation and killing the cell. The radiation does not extend far beyond the cancer cell, so there is little damage to surrounding tissue.

The international, randomized Phase 3 VISION trial, led by PCF-funded investigators Dr. Michael Morris (Memorial Sloan Kettering Cancer Center) and Dr. Oliver Sartor (Tulane University), enrolled more than 800 patients with mCRPC whose disease had progressed on other treatments. Patients also had to have a positive PSMA PET scan, meaning that their prostate cancer cells showed the PSMA protein on the surface. Patients were randomized to treatment with ¹⁷⁷Lu-PSMA-617 + best standard of care vs. best standard of care alone.

The study results were positive. Patients treated with ¹⁷⁷Lu-PSMA-617 were approximately 40% less likely to die and 60% less likely to have disease progression on scans vs. patients treated with standard of care alone. Median overall survival was 15.3 months for patients in the ¹⁷⁷Lu-PSMA-617 arm vs. 11.3 months in the standard of care alone arm. Other measures in the trial also showed a significant benefit for ¹⁷⁷Lu-PSMA-617.

In terms of side effects, some were more common among patients treated with ¹⁷⁷Lu-PSMA-617 + standard of care vs. standard of care alone. These included fatigue (49.1% vs 29.3%), bone marrow suppression (47.4% vs 17.6%), dry mouth (39.3% vs 1%), and nausea/vomiting (39.3% vs 17.1%).

¹⁷⁷Lu-PSMA-617 has not been approved by the FDA, though this trial data will be used as part of an application for FDA approval.

PCF congratulates the investigators on this ground-breaking development. PCF has funded over 80 investigations into PSMA biology and as an imaging and therapeutic target (including 2 earlier clinical trials of ¹⁷⁷Lu-PSMA-617) since the foundation’s inception in 1993, investing over $28.5 million in total. PCF is greatly encouraged that PSMA therapeutics has progressed so far.

Read more about the discovery of PSMA here.