Alicia Morgans: Hi. I'm so excited to be here at APCCC 2022 with Dr. Oliver Sartor, who's the Medical Director of the Tulane Cancer Center. Thank you so much for being here today, Dr. Sartor.

Oliver Sartor: Glad to be here in beautiful Switzerland.

Alicia Morgans: It is beautiful, absolutely. We're here to talk about a really important topic, which is implementation of PSMA theragnostics. The therapeutics, but also, of course, the imaging that goes along with it. I'd like to hear your comments on this because I would say the approval of lutetium has really taken the field by storm, and really helping us as a field think through how do we actually get this drug to patients is a big question that I know you will have some insights into. So please, where do we start with implementation of treating patients with lutetium?

Oliver Sartor: That's a really good question. I think I'll start with imaging because that's going to be one of the foundational issues. So, within the FDA label, there was a specification for imaging, as there was in the VISION trial, not a surprise. Not a surprise also was the PSMA-11 Gallium 68 imaging was specified. So, the other imaging with F-18 that is done with a Pylarify scan was not within the label, and that's caused some consternation because many patients have had the Pylarify scan but have not had the PSMA-11 Gallium 68 scan. And then, to confuse things perhaps even a little bit more, there was reference to a scan called Locametz from Novartis that is different than the Illuccix from Telix, and that was also brought into play for many people who've seen it for the first time. So, the first thing you do is have to get scanning and the way the scanning needs to be done, if we're going to follow the label is the PSMA-11 Gallium 68, regardless of the manufacturer and trade name.

Now, if we look at that and just briefly going back to VISION, you must have metastatic disease that uptake greater in the liver and must have areas that are PSMA negative, not present in terms of visceral disease, more than one centimeter, lymph nodes greater than 2.5, lytic bone lesion, soft tissue component more than one centimeter. So, remember there is a CAT scan selection process that ought to be implemented because if you end up with these PSMA-11 negative images and negative means less than liver, then those are probably not good candidates for therapy. Okay. Imaging is required.

Now secondly, therapy, of course that's required. And it turns out that you, first of all, need an arthritis user, somebody who is going to be properly licensed for the administration of radionuclides, particularly lutetium 177. That requires not only an authorized user, but a particular license. So, the licensure has to go through your state licensing board to be able to have that isotope on your campus, to be able to administer to patients in a commercial fashion, different by the way, than the experimental license that's required, if you're going to participate in protocols.

So, it's a commercial license, not the experimental license. So, your licensure, you're authorized user, now where we're still in the process of working it out is the insurance reimbursement and the appropriate codes. And I'll simply say that this is a very evolutionary process. I'll simply say that Novartis has teams ready to help to be able to move people from the experimental sort of vision type patient into the commercial phase. And I'll simply say that is now ongoing. So imaging, authorized users, licensure, and then of course getting the insurance and reimbursement down and that's in process.

Alicia Morgans: So just a few steps to trying to get the drug to patients, just to focus on imaging for a second. I think we just need to be really clear. We have to use a Gallium agent to actually identify these patients. So, a Gallium 11 PSMA PET must be done. And so, as you said, there are two options for this right now, if people are going to be buying a commercial product. So that's really, really important and who knows may change over time, but this is the label as it stands currently. Now, when you think about identifying patients, because this is really just the logistics in the background, how are you identifying patients? Because one of the other issues that we I think are facing is that there are long lines, at least at, at our institutions of people who have been waiting for this treatment, saw the approval Now feel like they want to get the treatment and it's still not for most centers available per standard of care. You know, as of this moment, of course we're coming online, but it's been hard. So how are you coping with that? The, the lines of patients and selecting patients to get treatment?

Oliver Sartor:  Well, there are a couple of issues. So first of all, and I think this will be a little bit of a review for some, but the pre-treatment requirements are very clear. Number one is this has to be metastatic, castrate resistant, prostate cancer. The individual should have received a novel antigen access targeted therapy. That'll be things like enzalutamide, darolutamide, abiraterone, and have progressed. And then also progressed after at least one taxane-based chemotherapy. So first of all, it turns out that some of the demand are actually coming from patients who are not eligible for the treatment, because they may not have had a prior taxane or maybe they don't have metastatic disease. So, there's some of the patients who are in line that probably ought not to be. Secondly, and I'm going to simply agree with you, Alicia, there's a bit of a rigmarole and frustration about trying to get patients on.

I do have three centers who are up and going now and I'll simply say that those three centers have been recommended by Novartis as being potential centers to refer patients to, but I don't actually know where they are, and they may be overwhelmed as well. So, we actually had a substantial list of patients that we're looking forward to being able to get commercial products. And what quite frankly we're doing right now is we're trying to create a little bit of delay and there's some people that have not seen cabazitaxel for instance. And you know, if we look at patients, we have direct data coming in from prospective randomized trial.

The cabazitaxel can provide value here and certainly cabazitaxel should be an option for some of these patients while we're waiting to get all the commercial things intact, external beam radiation for the palliation, of course, and make sure that you've looked for the precision medicine opportunities, making sure you're looking for the PARP inhibitor indications, making sure you're looking for the mismatch repairs who may be appropriate for pembro and by the way, I had one patient referred in, evaluate him, and what did we find? We found a very high MSI and his MSI is not only high, his TMB was very high. I put him on pembro and he's now had a complete remission.

So don't forget about the other options that potentially patients had not been evaluated for. We're moving forward, with fits and starts [inaudible 00:07:26]. And we certainly have more room for improvement.

Alicia Morgans: I agree. And, and we may have more opportunities to treat patients on label in the near future or hopefully in the near future. There's a lot of work being done, looking at lutetium in other disease states. I know you had mentioned a couple of studies that you're looking out for that may ultimately lead to a broader indication for lutetium.

Oliver Sartor:  Absolutely. There are three prospective randomized trials now that are looking at the pre-taxane, if you will, metastatic CRPC space. So, no prior taxane required. One of these is the SPLASH trial that is coming in from Point Biopharma. Another is PSMA four trial from Novartis and another is from Curium, which has the ECLIPSE trial. And it turns out the PSMA four is opening a number of spots, SPLASH is now opening a number of spots. ECLIPSE is now coming on board, and we don't have an exact time for a readout. So, I'm going to hesitate to give exact moments, but nevertheless, we can anticipate probably something next year. And if we hear from these PSMA four sort of SPLASH trials, then the opportunity to move the PSMA lutetium 177 up is going to be a real possibility. So, we're existing in a particular moment in time. Here we are in beautiful Switzerland. We are here during the end of April 2022. It's a very particular moment in time. I think you can come back, and we can do this interview two and three months later. And I think it'll be a little bit different answers cause we have worked out some of the logistics related to both the imaging and treatment and we're going to look forward also to the new trials we're going to probably report next year.

Alicia Morgans: Absolutely. Well, I sincerely thank you for your time going through how you're thinking about logistics, how you're choosing patients and helping to tide them over with therapies that we know can, can prolong survival and improve quality of life and really how we can look forward to an expanded indication potentially in the future pending these trial results. Thank you so much for your time and your expertise.

Oliver Sartor:  Thank you Alicia.