Pluvicto The First Targeted Radioligand Therapy for Treatment of Metastatic Castration-Resistant Prostate Cancer FDA Approved - Charles Ryan and Alicia Morgans

March 23, 2022

Drs Charles Ryan and Alicia Morgans discuss the approval of PluvictoTM (lutetium Lu 177 vipivotide tetraxetan) (formerly referred to as 177Lu-PSMA-617). Pluvicto was approved based on the pivotal Phase III VISION trial which evaluated men who had post androgen receptor pathway inhibitor therapy and post docetaxel or docetaxel and cabazitaxel chemotherapy, who were randomized to a protocol-defined standard of care with or without lutetium-177-PSMA-617.


Charles J. Ryan, MD, President and Chief Executive Officer of The Prostate Cancer Foundation (PCF), GU Medical Oncologist with expertise in the biology and treatment of advanced prostate cancer.

Alicia Morgans, MD, MPH, GU Medical Oncologist, Dana Farber Cancer Institute, Boston Massachusetts

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Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU medical oncologist at Dana-Farber Cancer Institute. I'm so excited to talk today with Dr. Chuck Ryan, who is the CEO of The Prostate Cancer Foundation and who is here to talk about some really incredible breaking news on Lutetium PSMA 617, or at least that was its former name. Can you fill some little bit on this, Dr. Ryan?

Charles Ryan: Yeah. Hi Alicia. This is breaking as we're recording this within the hour or so of this approval coming across, and it's an important step forward for men with prostate cancer. The Prostate Cancer Foundation has its fingerprints on this a little bit and I'll talk about that in a second, but just to give the headline, Novartis is a product, which is Lutetium-177 has been approved under the trade name Pluvicto and that is the therapy Lutetium-177, and that's been approved for men with metastatic castration resistant prostate cancer who have tumors that harbor PSMA expression. And PSMA expression is detected with the scan and there has been a second approval at the same time of the Gallium-68 scan also from no Novartis and the trade name for that is Locametz. L-O-C-A-M-E-T-Z, which is a pretty clever name when you think about it for a diagnostic test that's going to help localize metastatic lesions and the PSMA PET scan would then define the tumor as PSMA pet positive, which would drive the use of the lutetium therapy.

Alicia Morgans: So thanks for walking through that. So we have new names to think about, but I just want to make sure that we emphasize the patient population for this initial approval of Lutetium PSMA-617. So this is patients who have metastatic castration resistant prostate cancer that is PSMA PET positive. The agent that's used to determine that PSMA PET positivity is not mandated, at least as far as we can see now, but there is this Gallium-68 PSMA agent, Locametz that is available for that use, if we choose to use it. And all patients who are technically approved for this treatment with lutetium, actually have to have had progression of disease after an AR targeted agent or on an AR targeted agent and docetaxel. So that's the label as we see it right now. Is that your understanding too, Dr Ryan?

Charles Ryan: That's exactly right. And this is based of course, on the vision trial, which was a phase three study. You were a participant in that study, I believe, in which patients were treated with the lutetium treatment versus the standard of care or best supportive care during that time. And that study did show a 38% reduction in the risk of death and that was a statistically significant reduction. Many patients experience objective responses to this treatment, meaning their PSAs go down, measurable tumors will shrink and so we know that it has significant anti-tumor activity. Just to put a little more detail on your comment. Also, PSMA positivity is seen in about 86% of men in this space with metastatic CRPC. So this is not a rare biomarker where we're going to only be able to treat 10 or 15% of patients. This is the vast majority of patients in this post chemotherapy, post AR targeted space and that's one of the reasons why this is such a significant improvement, because really in that space, there's almost nobody who is not eligible to receive the treatment.

Alicia Morgans: Yeah, that's a great point. And I think patients who are in that situation, patients who have already had progression on those other agents really did need, still need great treatments, but having this option for them, I think, is so important as they're trying to make these decisions and I'm glad I think we've all been waiting to have the opportunity to use this drug in this setting in an FDA approved way, not just on a clinical trial. As we think about using our PSMA imaging agents to try to identify eligible patients, because that is going to be a requirement, I think it's important too to think about how we got to where we are and think about imaging, think about the theranostics or this treatment approach. And I know the PCF has actually had a lot to do with that. Would you mind just sharing with us kind of what your perspective is being with the PCF?

Charles Ryan: Well, I don't remember the year off the top of my head and I apologize for that, but the PCF has been funding research into PSMA for over 20 years. And this is a molecule that's on the surface, as I just said, at about 85% of prostate cancers and we have had many efforts and we have funded many efforts to try to target it over the years. I will just put it out there that, this is probably not the last agent that we're going to have that's going to target PSMA and there are other opportunities to target this molecules that's on the surface of almost every prostate cancer cell. There may be immunotherapies, cellular therapies, all kinds of things coming along the way.

But the discovery of this did come in part through funding through The Prostate Cancer Foundation in the late 1990s. Many of the investigators who helped identify this are still working on this age, are still working on this target around the world and deserve a lot of credit, but it is really a wonderful achievement for the field of prostate cancer. It's a huge achievement, I think, for the field of radioligand therapy and for nuclear medicine as it enters into more and more of the daily care of patients with not only prostate cancer, but other common cancers as well. So it's a really exciting day. I have a practice, you have a practice, I'm looking forward to being able to offer this to my patients, many of whom don't have other options, especially after chemotherapy and that's one of the other reasons why it's really exciting.

Alicia Morgans: To that point, I think it's important to just acknowledge that this agent is actually really well tolerated from what we can tell from the adverse event profile and of course, I have been fortunate to have some patients on the vision trial. So in my experience, it's been well tolerated, but we should make sure that everyone's aware that we do need to watch blood counts and that there, I think there may be some best practice limitations on what we want to do in terms of minimum hemoglobin, minimum platelet count and certainly the field has already been buzzing with what some of those numbers are, but really investigating that, making sure that teams are working together as multi-disciplinary units and having the oncology team work with nuclear medicine or radiation oncology, wherever this is being delivered, to make sure that our patients are safe, because even though it is really quite effective and well tolerated, we do want to make sure that we're within safety parameters when we're using the drug.

Charles Ryan: Yeah. And just for the sake of completeness, we didn't mention it. It's intravenous, it's given every six weeks and in the trial, it was only given for six times and then the study was discontinued. To your point, it does have some properties that sound a little bit similar to chemotherapy, marrow suppression, some anemia as part of that marrow suppression, fatigue and even a little bit of nausea was reported in the clinical trials. These are all areas where we can manage those things with supportive care. And I think, compared to some of the chemotherapies we give against cancer, this is quite a bit safer, but we look forward to reading, hearing and studying more on this agent than it's a significant impact on the field.

Alicia Morgans: Absolutely. So a great day for patients with prostate cancer. Congratulations, of course, to the team that's done the work and the patients who are engaged, but I think really just such an important advance and another call for us as a field to work together in multidisciplinary care teams and really another opportunity for us to provide the best care for our patients.