Highlights: UCLA/UCSF Inaugural PSMA PET and RLT Conference - Jeremie Calais

January 30, 2024

Jeremie Calais joins Phillip Koo on UroToday where they discuss the first annual PSMA conference hosted by UCLA and UCSF in partnership with Prostate Cancer Foundation. (PCF).  The conference topics include PSMA theranostics in prostate cancer and aim to leverage early experiences and global collaborations in PSMA clinical use. It featured a multidisciplinary panel of experts from around the world, focusing on PSMA PET imaging and targeted therapy. Key topics included diagnostic uses of PSMA PET, addressing potential false positives, and comparing various PSMA-targeting PET agents. The therapeutic segment delved into the future of PSMA-targeted radioligand therapy, exploring combinations, new targets, and the potential for improving patient selection and treatment outcomes. The conference underscored the evolving landscape of PSMA theranostics and its implications for clinical practice and research, with plans for annual meetings to continue advancing the field.

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Jeremie Calais, MD, MSc, Director, Clinical Research Program, Ahmanson Translational Theranostics Division, UCLA

Phillip J. Koo, MD, FACS, Division Chief of Diagnostic Imaging, Banner Health MD Anderson Cancer Center, Arizona

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Phillip Koo: Hi, my name is Philip Koo and welcome to UroToday. UCLA and UCSF hosted the first annual PSMA conference, which was a huge success, widely attended, amazing discussions, and really a lot of great actionable information for people interested in PSMA to take home and move forward with at their respective institutions. For those of you who were not able to attend, please check out some of the conference coverage articles that are located on UroToday for more details. So first off, Jeremie, thank you very much for being with us today, and can you give us some of your overall thoughts about the meeting and how it went?

Jeremie Calais: Thank you, Phil. Thank you for having me. A pleasure to be here. Yes, it was a great conference. This was the idea of Thomas Hope at UCSF. He wanted to leverage all the initial and early experience UCSF UCLA had in the PSMA theranostics clinical use, and also all the connection through research we made with our collaborators across the world, mostly in Germany and in Australia. So with the help of Wella Ballon, Johannes Czernin at UCLA and PCF, UroToday and all those sponsors, we were able to put that first inaugural conference. We had great speakers, very dense content. We broke down the conference in two days. Day one was more about PSMA PET imaging, and day two was more about PSMA targeted therapy.

Phillip Koo: I think that was a wonderful part of the meeting is you guys had a multidisciplinary group of experts and really global experts, Australia, Europe, US, which I think provided that global perspective on something that is so important. So let's focus on day one and the diagnostic use of PSMA PET. What were some of the highlights in those areas that I think from your perspective, really created more buzz than others?

Jeremie Calais: So we had these, our great expert speakers who gave the most current up-to-date overview of the past and current clinical data available. And so I think this reflects the truth and the current landscape. The main questions that triggered more discussions and discussion points were probably the false positives in the bone. In the ribs, for example, you can have false positives, so what are the causes? How can you address that, how do you communicate around it, what is the frequency to address a lot of that.

Then it was about now that we have all these different PSMA PET tracers available commercially and approved in Europe and in the US. So Gallium-68, PSMA-11 DCFPYL, PYLARIFY from Lantheus, Gallium-68, PSMA-11, also by Kit-based methods from Telix, from Novalis, and also recently in the US RHPSMA 7.3 Posluma Blue Earth diagnosis. Also, PSMA-1007 in Europe, ADX.

So we have all these PSMA-targeting PET agents. So how does this impact the clinical management, this was also a topic of debate. The take-home message is that globally it doesn't really impact both for patient selection to radioligand therapy for a treatment stage of staging or restaging. There are just some pitfalls we may want to avoid or just be aware of. The urinary excretion is less with PSMA-1007 and RHPSMA. So it's maybe better for the analysis of the prostate fossa. There may be more false positives in the bone and in the ribs with PSMA-1007 and maybe RHPSMA 7.3 as well. And for therapy selection to PSMA radioligand therapy, because the liver background is not the same with PSMA-1007 and RHPSMA, we may have maybe to use a spleen or at least change a little bit the way we assess the positivity of the PSMA-target expression.

So that was the key. Let's say the reading messages then now it's a lot about what will be the next indication. So biopsy guidance may be a case. For example, Louise Emmett from Australia is conducting studies showing how to read or perform the analysis of the PSMA uptake within the prostate with the primary score. So I think that's maybe one of the next stages, moving to the earlier stage within the intact prostate, the uptake.

And then it's now that we have robust knowledge on the diagnostic performances of these PET imaging tracers, how to use this new information for the best treatment outcomes. This is still unknown because, of course, this is recent. So we don't have outcomes to know what is the best. And so we discussed a lot about how to incorporate these findings into the treatment algorithms.

Phillip Koo: That's really exciting. We have real-world use of PSMA-PET, and this bone false positive has been a problem across the globe. And it's great to see that sort of being discussed. And then it's also nice to see how we're investigating now the nuances in biodistribution and figuring out what that means for patients, how it might impact decision-making, just lots of different impacts that this could have. So I think it's really exciting to know that the excitement and the potential future for diagnostics is still, we haven't met that potential and there's still a lot more to come.

What's also exciting is obviously day two and discussions about therapy, PSMA-targeted therapies. Lots of discussion about this with PSMAfore and other trials like SPLASH about to read out soon. So can you give us some of the highlights and takeaways from day two focused on the therapeutic aspects of PSMA?

Jeremie Calais: Right. So the structure of day two on PSMA diagnostics was more or less the same. We started with showing what we know. So what is the treatment landscape in MCRPC that is getting really huge table of different treatment options that patients have now. So we started from that. Where is PSMA targeted or other ligand therapy has been effective with the VISION trial? So we started there and then what will be the future and what are the unknowns?

And so the main thing is after the VISION trial, which is in patient who failed chemotherapy, all the major industry-sponsored trials now using PSMA targeted or other ligand therapy, are trying to move at earlier disease stages pre-chemotherapy before patients try chemo. So we have SPLASH, we have ECLIPSE, and we have PSMAfore from the three main sponsors. So we have the key principal investigators of these trials at the table discussing the protocols, what are maybe the differences, how it'll look when we move at earlier disease stage, what can be the toxicity, the weight of the toxicity that increase.

The more you go at earlier stage, it's not the same. And when you treat late-stage patient, and we don't know yet the long-term toxicity. For example, on the kidney, on the bone marrow, we don't have really a good collection of that. So that was discussed.

Then it was how can we improve the use of PSMA-radioligand therapy? There is a lot of potential because we can see the treatment with imaging, SPECT imaging. So how can you use that to do dosimetry, how we can use that to do sequential tumor response assessment and act on it with different treatment administration schemes.

We also talked a little bit about the selection for PSMA-radioligand therapy. That was a bridge to day one on how the different PSMA-PET tracers can impact or not the selection for PSMA-targeted-radioligand therapy. And then it was about more, let's say, not futuristic, but it's maybe where the field is starting to move. Combination with AR-targeted agents, new targets. We had all this discussion about what is upcoming. So it was really about combination, new targets, what is the role for example of Radium-223 in that landscape, the sequencing of the treatment, the improvement of the administration scheme, treatment activity, time interval, all these things that we don't know yet really what is the best way to do.

Phillip Koo: That's really exciting. PSMA therapies, I think we have looked at it very simplistically as, oh, someone's PSMA positive, someone's PSMA negative. But it's really nice to see how the community is really looking at it more elegantly, looking at nuances. How do we do patient selection better? The idea of using post-injection imaging to sort of tailor our doses. I think all this stuff I think will eventually lead to better outcomes for our patients. So any final takeaways? Where are we moving as a group when it comes to PSMA, and what's the message that you have for all the listeners who might be thinking about ideas or other trials that they might want to start locally?

Jeremie Calais: So I think there are really two ways to look at how to use the PSMA theranostics-related technologies. You have how to implement it at best in your daily current clinical practice. And then you have, what are the next questions to answer in clinical research? These are really two different things.

First, I want to say that we had a session on how to build a theranostics program with nurses that came that explained the logistic nursing relation safety implications. It was really ground-based session, and I think it was also well appreciated by the audience.
I think also our tumor boards we had on day one and on day two, PSMA PET tumor board and PSMA targeted radioligand therapy tumor boards with all these experts. We showed cases. They were giving their opinion. Many people consider this really the highlight of the conference. So we'll do that again next year. Next year it'll be at UCLA this time. We want to do that, a yearly conference, one day at UCSF, one day at UCLA. So we'll hope that you'll be able to join because there are still many, many things to learn in the future.

Phillip Koo: Well, great. Thank you very much, Jeremie, for giving us this overview. For the listeners out there, be sure to check out some follow-up videos that we have that record specific presentations from those who presented at this meeting. And mark your calendars. I believe in 2025 it's at UCLA. So a good reason to come visit Beautiful Los Angeles. So thank you very much, Jeremie.

Jeremie Calais: Thank you, Phil, for having me. Always a pleasure. Thank you.