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Chuck Ryan: Hello. Today we are talking from ASCO 2019 in Chicago and I'm delighted to be joined by Dr. Oliver Sartor from Tulane University. Oliver, always a pleasure to speak with you. I want to talk a little bit about the lutetium studies. You're heavily involved in this. You've been a proponent and an advocate and a champion of radioligand therapy for some time, both in terms of radium and perhaps now lutetium as it's coming through clinical trials. Tell us about the state of where we are with lutetium in the United States right now, globally.

Oliver Sartor: Well, we might be further advanced than you think and I think this is a little bit interesting. It turns out, the PSMA lutetium story really predominantly broke in Germany. It was pioneered there and the initial treatments were done there and there were opportunities that developed around peculiar German laws that allowed compassionate use even of radiopharmaceuticals.

There's a whole cottage industry now of the Germans allowing compassionate use. Things like PSMA lutetium. The problem is that there really weren't any proper trials until, and I would give full credit to Michael Hoffman down at Peter Mac in Melbourne, who did a proper trial, small but important trial of looking at PSMA lutetium. Actually, it looked pretty damn good. Actually, before his trial broke, there were a series of discussions about how to really do this as a proper clinical trial.

Chuck Ryan: Right.

Oliver Sartor: Well, the first problem was that the intellectual property was not owned by any particular entity. It was sort of a diffuse set of arrangements that was actually a German subsidiary of a Japanese company that didn't know what to do with it. Through discussions with a little company called Endocyte, who is already doing some PSMA work and I was involved with them, I had a long discussion with the executive leadership and explained how to go about getting this particular compound.

Those guys pulled it off and they wrapped up the intellectual property. You cannot do clinical trials without intellectual property protection. They got it. Now subsequently, they've been taken over by the huge Swiss company, Novartis and so that's an endorsement about their intellectual property. In the meantime, we had to design the trial and the decision was going to go straight to phase three. It was called the VISION trial. The VISION trial, believe it or not, is going to be closing this summer.

Chuck Ryan: How big a trial is it?

Oliver Sartor: 750 patients.

Chuck Ryan: Amazing. I'm not surprised actually.

Oliver Sartor: Well, no. It's accruing like crazy. It's a pretty simple design built in part on the radium and part due to interactions with the FDA. Standard of care, but the eligibility requirement includes either you've had abi or enza ... Excuse me and docetaxel. You have to have gone through standard therapies and then you're randomized to standard of care, which could be pretty much anything you want to do that's FDA approved.

We did more experimental therapies obviously. Plus or minus the PSMA lutetium 177. It's a pretty straightforward trial. There's a dealer's choice when it comes down to what the physicians want to do. They can do anything they want.

Chuck Ryan: It's monthly treatment, correct?

Oliver Sartor: Every four weeks for a total of up to six. After four cycles, there are no additional cycles unless there's the perception of clinical benefit and the individuals who have clinical benefit can go on to receive two more cycles. PSMA scan selected, I need to mention that.

Chuck Ryan: Right. They have to have a positive PSMA PET scan, which basically is another way of saying they have to have PSMA expression in their tumor because that's the drug target.

Oliver Sartor: Absolutely.

Chuck Ryan: What should we be concerned about with respect to lutetium? It sounds very encouraging and I've seen people being treated and I'm a strong advocate for the trials, but anything that you think we need to be worried about?

Oliver Sartor: Well, there is always with any radiopharmaceutical, I think the potential for long-term toxicity. That's always been a concern for every form of radiation. You may end up with some bone marrow alterations. However, I'll tell you that the actual cytopenias that are seen during the course of therapies have been pretty minimal. There's been some salivary gland issues and very occasionally some lacrimal gland issues.

Chuck Ryan: Okay.

Oliver Sartor: There's some PSMA localization. If you've ever seen a PSMA scan, and I know you have, where you see the salivary glands and these lacrimal glands that will light up and there are a few changes in those glands in the trial, but not too much. If you really want to know the truth toxicity wise, we've not seen very much.

Chuck Ryan: We've only given it so far to people with advanced disease and high PSAs from my understanding. One of the concerns is, is there a risk in lower PSA disease, let's call it, where there may be lower PSMA expression and the ratio or the dose if you will, of radium to tumor may be different. Is that a concern?

Oliver Sartor: Well, it's a very significant concern. One of the things we've learned over the years is that androgen deprivation may actually increase the expression of PSMA, but it turns out, and if you go to the PSMA scans that are now being done at UCSF, UCLA, and many other places, that it turns out once you get a PSA in a recurrent setting of above one or two that virtually everybody is PSMA positive.

Chuck Ryan: Okay.

Oliver Sartor: The question is, how good are targeted ... Now, we're designing a future trial and I don't want to get ahead of myself, but there is another trial with Alliance and NRG cooperating with Alliance taking the lead, that involves the hormonally sensitive patient and using an ADT, abi and then plus or minus the PSMA lutetium.

I think that's a very, very intriguing trial concept, to bring it up to the front. One more thing on the upfront, which is interesting and has not been widely presented. It was presented last year at the EANM meeting, European Association of Nuclear Medicine in Dusseldorf. I happen to have gone. They're using a little bit in the hormone-sensitive setting and the results look quite good perhaps even equivalent of ADT.

Chuck Ryan: Oh, great.

Oliver Sartor: Yeah.

Chuck Ryan: Interesting.

Oliver Sartor: That that would be a remarkable game changer.

Chuck Ryan: Right, right, right.

Oliver Sartor: We'll see. I mean, I don't want to get the cart in front of the horse, but there's some intriguing work going on out there.

Chuck Ryan: Exciting times. It's really interesting to hear about the VISION trial, which I think nobody doubted would be a rapid accrual. We'll have to just wait and see how the data look over time and I'm sure you and I will get a chance to sit down and talk about this in the future.

Oliver Sartor: I suspect so.