Michael Morris: Thank you, Neeraj. It's a pleasure to be here.
Neeraj Agarwal: First of all, congratulations, Mike, for presenting the quality of life data from the phase three PSMAddition trial. Please tell us more about PSMAddition trial first before we get into the quality of life data.
Michael Morris: Sure. PSMAddition is the third registration study for Pluvicto. The first was VISION, which focused on the patients who had APMR, as we're calling it now, per prostate cancer working group four, which used to be CRPC, and that was in the post-chemotherapy context. The second registration trial was PSMA-4, which was in the pre-chemotherapy context of APMR. And PSMAddition is in the APMN or APMS, which we used to refer to as castration-sensitive disease. For those who were PSMA avid on a gallium-68 PSMA PET scan, the design of the trial was randomization on a one-to-one basis to either ADT and an ARPI, either with or without up to six cycles of lutetium-177 PSMA-617 or Pluvicto. And the primary endpoint was radiographic progression-free survival with secondary endpoints of overall survival and also patient-reported quality of life, pain, and time to SSE. So just to remind the audience today, it was a positive study for RPFS, the primary endpoint.
Those results were presented at ESMO. And the hazard ratio in favor of treating the patients with the triplet therapy of lutetium ADT and an ARPI was 0.72 in favor of the triplet. So when you have a positive finding based on an outcome like that, it's really important to know. So you've increased the duration of disease stability. What was the experience of being a patient with prostate cancer on the two arms of the study so that you can see how patients felt and functioned during that period?
Neeraj Agarwal: So in this meeting, in the ASCO GU 2026 meeting, you presented the quality of life data from the phase three PSMAddition trial, which met the primary endpoint of radiographic progression-free survival improvement in a significant fashion. So before we get into the quality of life data, what kind of tools were used to measure these quality of life parameters? Michael Morris: So we kept all of the studies as close as we could. So we used the same tools that we used in VISION and in PSMA-4. For quality of life, we used two PROs. One was the FACT-P, and the other one was the EQ-5D-5L utility score. For pain assessment, we used the brief pain inventory short form. And we really are trying to keep all of these comparable so that we can cross-compare, but we used also the same definitions of the cutoffs for a time to decline in quality of life and pain. So those were the identical tools we had presented at ESMO already the time to decline in quality of life and pain.
And I think that, to be honest, a lot of people walked away with a misunderstanding of those data. So when they were looking at those quality of life curves for especially the EQ-5D-5L utility score and FACT-P, the curves did appear to diverge in favor of the doublet versus the triplet therapy. And what I think people walked away from ESMO thinking is because those curves diverged and remained separate, that quality of life must have been consistently inferior on the triplet arm. But that is a time-to-event assessment. Those curves that were presented to ESMO reflected time. And once your quality of life erodes on a time-to-event endpoint, it's non-recoverable. So once a patient's quality of life declined at a certain point in treatment, even if their quality of life improves, it's not like those curves will come together because the endpoint was met of time to decline. So I have just heard today, in fact, on the podium, someone refer to those data and say, "Oh, look, the quality of life was worse on the treatment arm as opposed to the control arm throughout the duration of treatment." In today's presentation, it's not a time-to-event analysis. You can see the quality of life data at each successive data collection point and see that in actuality, quality of life followed longitudinally is dynamic and variable depending on where you were in treatment.
Neeraj Agarwal: So when you are giving the first six cycles of Pluvicto-
Michael Morris: Yes.
Neeraj Agarwal: ... patients may experience those side effects.
Michael Morris: That's right.
Neeraj Agarwal: But following that, better disease control may result in normalization of quality of life.
Michael Morris: And so what you actually saw, dependent on the PRO. So for the FACT-P ... First, I should say that we have good data from randomization to about 25 months of therapy. The median follow-up at this data cutoff is just about 24 months. After 25 months right now, we only have like double-digit data per arm, but at 25 months or 108 weeks, we have triple-digit data. So let's just talk about randomization to 108 weeks. What you just said about the quality of life diverging for the FACT-P is exactly right. When you're on three drugs, your quality of life is somewhat poorer than if you're on two drugs. Once that 36 week or six cycle period is over, the curves essentially reconverge, and so quality of life is really, really close to each other once everybody is on the doublet therapy once again after that initial 36 weeks where the treatment regimens are different.
I don't think we have enough long-term data, i.e., after that 25 month point to say what happens at the point of relapse, because we just don't have the data until that point. But I think that what you can say is for the FACT-P, quality of life goes down during the triplet portion versus the doublet, but once patients are all back on doublets, it's very similar. And for the EQ-5D-5L utility score, quality of life is the same throughout. And for the BPI-SF, quality of life is the same throughout. Time to SSE is the same throughout. There is this misconception, I think, from the original data that was presented at ESMO, which is as a time-to-event presentation. But when you look at the actual data, there really isn't a substantive or surprising quality of life difference between the two arms, especially after the period of where the active treatment with lutetium is being administered.
Neeraj Agarwal: So looking at the overall picture, is it a right way to summarize that patient's survival outcomes improve without compromising quality of life?
Michael Morris: I don't think we can say that yet until we get more survival data. But what I like about that question is, what is the totality of data telling us right now in terms of should we or should we not use Pluvicto in this very early clinical context? And for that totality of data, you want to be able to look at relatively mature survival data, quality of life data, and the primary endpoint of RPFS and see how they all line up. And what I would say is that right now, after 25 months, we don't have enough quality of life data, and we still don't have enough survival events to really answer that question completely or fully. So I'd say stay tuned on that. It's a trial that it's met its primary endpoint, but the question that you're asking is a clinical question, not a statistical question. And for those clinical data and those clinical endpoints to mature, we just need some more time.
Neeraj Agarwal: Well, thank you so much for explaining this so comprehensively. And again, congratulations for conducting a large phase three trial. It takes a lot to conduct these kinds of trials and for meeting the primary endpoints for radiographic progression-free survival with a drug which is already known to be effective in the mCRPC setting and now we are seeing the data in metastatic hormone-sensitive prostate cancer setting.
Michael Morris: Thank you, Neeraj. It's always a pleasure to both talk on UroToday and to talk to you.
Neeraj Agarwal: Thank you.
Michael Morris: Thank you.