But you'd have to say also we're not curing many of these people, but also, I think we're heading into a space where we're seeing diminishing returns from adding things on upfront, hence the controversy about whether we add docetaxel on top of an RP, for example. And also we're seeing a lot of new classes of drugs appearing, T-cell engagers, PROTACs, all sorts of other interesting things. How on earth do we test all of these things in the upfront setting? And actually I think the PEACE-6 trial is a very interesting example of, you don't test them all in the upfront setting, you just test them in the bad actors to see if you can intensify. And we've got trials running at the ICR at the Marsden where we're doing a very similar thing, but with SABR instead of with radioligand therapy. So I think that indicates one of the potential future directions of travel. So STAMPEDE2, currently two comparisons. There's others in discussion. And I'm going to talk about this one, which is the patients not eligible for SABR, i.e. more than five metastases. Randomization is standard of care, which is the Sinatra standard of care, which is to say you do it your way, versus standard of care plus six cycles of PSMA lutetium. Now, we would very strongly have the opinion that giving this PSMA lutetium over six cycles every six weeks, i.e extending well past six months, may be not the best way of doing this because we know the target is disappearing.
So we're looking at a more intense schedule where we give a cycle day one, day eight. So you've only got 13 weeks from shot one to shot six, starting within 12 weeks of commencing ADT. And the aim is to maximize dose delivery whilst the target is present. Linked to this, we've got dosimetry studies so that we can measure the dose, both to the tumor and to the normal tissue. One of the things we were concerned about was that we would see a tumor-sink effect and increased dose to dose-limiting normal tissue like kidneys. We've got an imaging study, dual imaging, because obviously if you image with PSMA PET, you're imaging the thing you're targeting. So that's not necessarily telling you about PSMA-negative disease. We're very keen on whole-body MRI scans as a separate way of doing this. So just highlighting a few things, because as I said, this is work in progress. I'm just giving you exemplar data. We've got around 40 patients in the imaging substudy at the moment. So we've got quite a lot of data. I can't really show you all of it at the moment. But what this shows, and this is just a random, not quite random, a patient on whom we just happen to have a nice set of graphs. And what we see is what we predict, which is the dose per lesion drops with each subsequent cycle. So one of the things we were, therefore, very interested in was, was there some sort of relationship between the dose per lesion and the PSA, i.e. Could we, for example, adapt therapy on the basis where they've had a good PSA response, we'll stop the treatment, reduce the normal tissue damage. So this is all data from one of our clinical fellows, Minal Padden-Modi, who I should have credited on this and I apologize to her. So this is a collection of early patients in the trial. Each vertical thing is the lesions in a particular patient plotted along the bottom on a log scale, you can see the PSAs.
Roughly the mean dose in gray, per lesion, anything below one is essentially background dose, we estimate. So if you project a horizontal line from a mean dose of one gray, you can see that as you get to lower PSAs, we've got a lot of lesions that are functionally getting no dose. They're just getting background blood pool circulation dose. But you can also see that even at nor 0.1, we've got lesions getting dose above the one gray line. And also quite strikingly, the patients, and again, this is a subset of something that's in progress. The highest doses per lesion are not being seen at the highest PSAs either. They're being seen in patients who are already down the path of responding. So suggesting that the response is associated with an upregulation of PSMA, and of course other people have reported this, as well. Looking at this in a slightly different way, we wanted to look at whether there was any dose present or not at a range of PSAs. And you can see that if you look at the dose absence, there are patients with really quite substantial PSAs where we can't measure any dose going into lesions. Conversely, there are patients with very low PSAs where we can nonetheless measure dose. It's a different version of the same slide that I just showed you. So the bottom line is we can't really use PSA as a way of saying whether or not patients are getting useful dose per lesion. All right. So we're also, of course, very interested in normal tissue dose. What we're doing is a phase-one trial. We've done a review of the dosimetry literature to see what the safe dose limits are for PSMA lutetium. There is essentially zero conclusive data on this. We don't know what the safe kidney dose is, for example.
What we've started constructing is nomograms of the range of doses that we see and we're plotting each individual patient onto there. So one of the things I'll highlight from this, if we look at the combined kidney dose, what we can see is that despite the dose per lesion dropping, we're not seeing an increase in dose going to the kidney. So we're not seeing a tumor-sink effect where you've got less tumor soaking up the dose, resulting in normal tissues getting a higher proportion of dose. And this has been very consistent across all of the patients that we've seen. You can also see that the liver doses are quite low. Salivary gland doses are variable. We're collecting quality of life data PROMs on dry mouth and so on. So we'll report whether this does or not correlate in due course. Again, this is relatively early data. So some of the patients, the ones on the right-hand side are still on treatment when we constructed this graph. What you can see is that we've got quite a big range of doses. Some of these patients got four cycles, some got six cycles at the point where we're reporting this. Patient one, in fact, they seem to be getting very high doses to the kidney, and actually we're getting no dose to tumor. So we actually decided on safety grounds not to give him the last two cycles. But apart from that, we're not really formally dose modifying, right? Just to whiz through some of the other things.
We've also looked at response, and of course I'm going to show you the best responses. So what you can see here is a patient getting a fantastic response from high-volume disease down to virtually a complete response. What I would highlight, though, is that this patient, nonetheless, still has uptake in his prostate. And then that's not an uncommon finding. Again, I haven't got time to go through all of this, but we've just got a tactical award from PCF, which I'd like to thank them for. And one of the things we're very interested in is the hypothesis that radiologically residual disease at best response is harboring the tumor clones that are going to ultimately kill you. And so we're going to essentially take biopsies of this and science the hell out of it to look at the radiomics of this, the correlative biological factors, integrative analysis, of all of that, and potentially we hope identify ultimately new targets that correlate with PSMA lutetium resistance. And to do that, we're going to do MRI-guided biopsies of the residual disease because the impaired diffusion lesions we know are pretty predictably cellular. This is from work done by my colleague, Johann De Bono, who uses this technology a lot in his resistant disease sites.
We've got a really well worked up pipeline for analyzing these samples, and this is my conclusion with nine seconds to go. So far, we're happy that the schedule we're using is feasible and safe. It is a phase-one trial. We've got a lot of emerging imaging and dosimetry data, which we think will inform future trial design. We've just got ethics approval to open in three European countries, hopefully in a fourth one in Italy shortly, as well. And just to highlight, we've got, well, a lot of people involved in this. STAMPEDE is a cast of thousands, just to highlight some of the key centers. Thank you for your attention.