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GU Cancers 2026 | TulmiSTAR-01: tulmimetostat with luxdegalutamide in mCRPC

Andrew Armstrong, MD, MS, Duke Cancer Institute, Durham, NC, comments on the Phase I/II TulmiSTAR-01 trial (NCT07206056) of tulmimetostat with luxdegalutamide versus standard of care in progressive metastatic castrate-resistant prostate cancer (mCRPC). This dual-targeting approach combines EZH2/EZH1 inhibition with proteolysis targeting chimera androgen receptor degradation to overcome resistance to androgen receptor pathway inhibitors. The study includes dose optimization and randomized comparison phases to assess safety, tolerability, and efficacy endpoints including prostate-specific antigen response and survival outcomes. This interview took place at the 2026 ASCO GU Cancers Symposium in San Francisco, CA.

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Transcript

So this goes right after the guidelines. In prostate cancer, one of the biggest issues is heterogeneity. You have tumor cells that are very AR-dependent right next to tumor cells that can diverge, undergo lineage plasticity through epigenetic reprogramming, transform into neuroendocrine prostate cancer, for example. One of those main mediators is EZH2, which is a polycomb repressor complex that regulates cell differentiation and AR signaling...

So this goes right after the guidelines. In prostate cancer, one of the biggest issues is heterogeneity. You have tumor cells that are very AR-dependent right next to tumor cells that can diverge, undergo lineage plasticity through epigenetic reprogramming, transform into neuroendocrine prostate cancer, for example. One of those main mediators is EZH2, which is a polycomb repressor complex that regulates cell differentiation and AR signaling. So the TulmiSTAR-01 trial is attempting to combine an AR degrader to target the AR positive cells with an epigenetic agent, an EZH2 inhibitor, all oral, to try to prevent or delay radiographic progression in patients that have metastatic androgen pathway resistant disease. And this is a phase one slash two study. It’s dose finding, followed by dose expansion, followed by randomization. So it’s a very large global trial. We have a trial in progress poster that talks about the endpoints and the layout and the clinical trial design.

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