Alicia Morgans: Hi, I'm so excited to be at AUA 2022, where I have the opportunity to speak with Dr. Neal Shore about the integration of Lutetium into our clinical practices, from a urologist perspective. Thank you so much for being here, Neal.

Neal Shore: Oh my pleasure.

Alicia Morgans: Wonderful. So, Lutetium is newly approved. It is something that so many patients have been waiting for and definitely clinicians as well. How do we take steps to really thoughtfully and practically, integrate this new therapeutic into our treatment paradigm?

Neal Shore: Yeah, very, very important. Now they're the first to do, it's a AAA, Novartis was the first to get the sponsorship with great leadership from Oliver Sartar and Mike Morris in the VISION Trial, we were fortunate to be a trial site, so we had experience with it. I did it together with my radiation oncology colleagues in a true multidisciplinary team way. I think that the world of theranostics where we take a radiopharmaceutical and link it to an antibody, in this case, PSMA, there will be other radiopharmaceuticals, other beta particles, other alpha particles, combining beta and alpha, so even some small molecules too. So this is really going to open up another entire class of therapeutic with a distinct novel mechanism of action, for our patients with advanced prostate cancer. The VISION Trial demonstrated survival benefit, RPFS benefit, delayed to additional therapies. Good quality of life on the therapy in our mCRPC post-progression novel hormonal agents, not post docetaxel taxine as well.

Trials are ongoing in multiple different sponsors with the different conjugates in pre chemotherapy, mCRPC and mCSPC. There are some investigator initiated studies looking at using this technology for biopsy, using it in the BCR population. It's very, very exciting. Of course, the trials have to get done, evidence, safety, like we usually do. But for urologists to radiation oncologists, Nuc Med radiologists, which is great for them, brings them into our multidisciplinary team. And most importantly, for patients, this gives another tool in the toolbox to help patients to live longer, live with the disease, not succumb to the disease.

There are going to be some challenges though. There's a type of a licensure that one has to get. This is going to be administered under the purview of Nuc Med radiologists or radiation oncologists. It's a different licensure, a radio activities materials license from radium 223, for example. Maybe sites that are familiar with that will have some facility in expediting their licensure. They have to work through the nuclear regulatory commissions of their individual states, regions, countries.

And then additionally, there are some other caveats about precautions for patients after they receive treatment. It varies in some countries. I know in Germany, for example, patients, it's an inpatient procedure. In the US, it's going to be outpatient, but there are different precautions. They're a little bit more stricter than say when you give radium.

But nonetheless, I think this is great. I think that all of our colleagues who treat prostate cancer regardless of your specialty, are going to be having a really full throated conversation in 2022, and with the approval of Lutetium 617, but then others that are going to be coming along. The trial landscape is really, really rich, will keep us really busy with plenary presentations and all the major congresses.

Alicia Morgans: Oh, well, I definitely agree with that, but I appreciate you kind of helping us think through some of these practical things. Can you talk to us a little bit about how we identify patients. Biomarker selection and using PSMA PETs to help us know which patients may benefit most. And really that's how the label is written, right? We have to get a certain kind of PSMA PET to use the drug. Can you walk us through that?

Neal Shore: Yeah, that's a really important point. So the patients who were enrolled in the VISION Trial, the phase 3 that led to the regulatory approval of Lutetium 617 PSMA, had to have a gallium PSMA PET positive scan. Now I think what we're going to find at least in the US, that we have other PSMA PETs, we have the 18-FPYL, there are going to be more to come. Looking at the reviews of papers and NCCN recommendations suggest that the PSMA PET, regardless of it's 18-FPYL are gallium, is that there's an equality to that. We have multiple different companies that are doing PSMA RLT trials. Some are more flexible regarding the type of PSMA PET gallium versus 18-FPYL and more to come.

So that's a little, maybe a different consideration. The good news is in the VISION Trial, 87% of patients had avidity for the gallium PSMA PET, so nearly 90%. But because there's some potential exclusion to do another therapy, you would like to know if you're in that 13%, so maybe you'd go into a clinical trial and not maybe undergo the cost of the therapy. But the good news is as for our patients right now, certainly in the US and other parts of the world where this is available, if they've exhausted taxanes, if they've exhausted novel hormonal agents, ABI, ENZA, APA, DARO, if they're not candidates for a PARP inhibitor, they can benefit from this PSMA RLT therapy.

Alicia Morgans: Absolutely. And so, as you said, the label for Lutetium actually really seems like it's recommending a gallium PSMA PET, but as you also said, the NCCN guidelines actually incorporated in that 18-FPYL PSMA PET as well. So I think we'll see how that settles out, but that is something to think about as we're trying to use Lutetium. Are there any other words of wisdom that you could share with urologists who are trying to get this therapy to their parent patients?

Neal Shore: Yeah, I think it's so important for my urology colleagues, not just in the US, but globally, who are taking care of patients with advanced prostate cancer, work with your radiation oncologists, your nuclear medicine radiologists. I think outside the US, our nuclear medicine radiology colleagues have done incredible work to advance the field. Of course, medical oncologists have to be integral to this as well. The main goal would be to cure the disease, and we know we really can't say that, but to make this a chronic disease, keep patients out of hospital, out of the emergency department. The overall tolerability of Lutetium 617 and other PSMA RLTs, is actually pretty impressive. And these drugs are administered once every six weeks, sometimes once every eight weeks, so it's not a very onerous schedule. So for urologist, this is another great opportunity to work with a multidisciplinary team.

Alicia Morgans: Great. Well, thank you so much for your time and for sharing your expertise and experience with Lutetium.

Neal Shore: Thank you.