GU Cancers 2021 | 177Lu-PSMA-617 for the early treatment of prostate cancer

So, we presented three clinical trials in progress at ASCO GU. These were UpFrontPSMA, LuTectomy, and Enza-p. They’re all studies using lutetium-177-PSMA-617 in a slightly earlier phase of disease compared to perhaps the TheraP study that we presented the results of, or the VISION trial that we are awaiting the results of. These trials are funded by a Movember Prostate Cancer Research Alliance, also with support from the Australian government. So, they’re all investigator-initiated studies. The ANZUP Cancer Trials Group is involved in two of these trials: the UpFrontPSMA and the ENZA-p trial. And I’ll run through all these trials briefly.

So, I might start with the UpFrontPSMA trial. This is a Phase II randomized trial, where we’re using lutetium-PSMA as an upfront treatment in men with newly diagnosed metastatic prostate cancer with high-volume disease. So, these are men that present with de novo metastatic disease. They must have metastases evident on CT bone scan and a high volume of disease defined on a PSMA PET-CT. And they are randomized to two cycles of lutetium-PSMA-617, followed by docetaxel chemotherapy, that’s the experimental arm, compared to docetaxel alone. And the primary endpoint of this study is a undetectable PSA at 12 months. Now, this is recruiting at 11 or 12 sites around Australia, a similar network to the TheraP study. This trial is underway and actively recruiting.

Another one of the trials is the LuTectomy study. This is a much smaller, perhaps, you’d call it a Phase I or II trial, a single-center study being conducted at the Peter MacCallum Cancer Centre where I work, and this is a trial led by Professor Declan Murphy who’s a urologic surgeon. In this study, we are assessing the utility of one or two cycles of lutetium-PSMA-617 prior to prostatectomy in men with high-risk, localized disease.

So, these are men with a Gleason grade group 3, 4, or 5 disease, with or without pelvic nodal disease. They must have high PSMA expression defined by an SUV max over 20 in the prostate primary. And then they have one or two cycles of lutetium therapy, and six weeks later, have a prostatectomy. The primary endpoint of this study is a dosimetry endpoint. So, men are undergoing SPECT/CT scans at three time points and using a voxel-based method, we are calculating the dose in gray delivered to tumor, and our hope is that we’ll be able to get meaningful tumor killing doses of radiation with lutetium-PSMA-617. This trial is also well underway actively recruiting.

The third trial we had a pleasure to present at ASCO GU this year was the ENZA-p trial. This is a study run by my colleague, Professor Louise Emmett, in Sydney. It’s another trial designed and conducted by the ANZUP Cancer Trials Group, running at our TheraP network of 11+ sites around Australia. This trial is a little bit earlier population than the TheraP study. This trial takes men with metastatic castration-resistant prostate cancer. They have to have high-risk features for early failure with enzalutamide, and they are then randomized one-to-one to either enzalutamide in combination with lutetium-PSMA or enzalutamide alone.

There is a lot of embedded PSMA and FDG scans in this study. So, after two cycles of treatment a repeat PSMA/PET scan is done, and that determines whether patients randomized to the lutetium arm continue to have a further two cycles of lutetium-PSMA-617 or if there is a rapid, complete resolution of PSMA uptake, then that is not given. The primary endpoint of this study is progression-free survival, so a really interesting study. It’s the first study combining both enzalutamide and lutetium-PSMA. The hope here is that this will be a synergistic combination. Professor Emmett has previously shown that enzalutamide results in upregulation of PSMA cell surface expression, so that may enable subsequent cycles of lutetium to even be more effective, so a really interesting trial. This trial also funded by Movember and the Australian government.

So those three together at three different stages really, from the earliest point in men with newly diagnosed with prostate cancer due to have a prostatectomy, through to men with newly diagnosed prostate cancer in the UpFrontPSMA trial. That’s a trial run by Professor Arun Azad at Peter Mac, and lastly, the ENZA-p trial. So, we’ll have some, hopefully, great data to present at upcoming ASCO GU meetings in the years to come.