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GU Cancers 2026 | LuxAR-02: luxdegalutamide and 177Lu-PSMA-617 in pre-treated mCRPC

Daniel Petrylak, MD, Yale University, New Haven, CT, describes the Phase II LuxAR-02 trial (NCT07047118) of the PROTAC androgen receptor degrader luxdegalutamide with 177Lu-PSMA-617. This trial enrolls patients with PSMA metastatic castration-resistant prostate cancer (mCRPC) previously treated with androgen receptor pathway inhibitors. The primary objectives are to identify the recommended Phase III dose based on safety and prostate-specific antigen response, and to compare the efficacy of the combination against lutetium-177-PSMA-617 monotherapy. This interview took place at the 2026 ASCO GU Cancers Symposium in San Francisco, CA.

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Transcript

So we’re looking for ways to improve the outcomes with lutetium-based PSMA therapy. And it’s been shown with studies such as VISION, where there was an improved PSA response rate, as well as radiographic progression-free survival in patients who received combination therapy with enzalutamide and lutetium versus enzalutamide alone. So ARV766 is an antigen receptor degrader, which potentially increases PSMA expression...

So we’re looking for ways to improve the outcomes with lutetium-based PSMA therapy. And it’s been shown with studies such as VISION, where there was an improved PSA response rate, as well as radiographic progression-free survival in patients who received combination therapy with enzalutamide and lutetium versus enzalutamide alone. So ARV766 is an antigen receptor degrader, which potentially increases PSMA expression. And this trial is designed to look at that question, whether giving ARV766 will actually increase the efficacy. It’s a small study, but whether we want to go forward and see if there is a signal that we can work with that shows that there’s improved outcomes rate.

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