Advances in PSMA-directed Radionuclide Therapy - Howard Soule

Howard Soule discusses highlights and his takeaways from the Advanced Prostate Cancer Consensus Conference (APCCC) 2019. Dr. Soule highlights the importance of coming to these conferences to understand where the gaps are in the treatment landscape and the benefit of these global conferences for clinicians from resource-limited countries. They continue on to discuss imaging, PSMA, and the VISION trial and a number of several ongoing trials with data emerging in the near future in advanced prostate cancer.

Biographies:

Howard R. Soule, Ph.D., Executive Vice President & Chief Science Officer, member of the Department of Defense Prostate Cancer Research Program Integration Panel. Most recently, he was Managing Director of Knowledge Universe Health and Wellness Group, a private investment firm focused on companies in the general areas of disease prevention and treatment. Dr. Soule has been with the Foundation for 19 years.

Alicia Morgans, MD, MPH, Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.

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Alicia Morgans: Hi. I am thrilled to have here with me today Dr. Howard Soule, who's the Chief Scientific Officer at the Prostate Cancer Foundation. Thank you so much for joining us today.

Howard Soule: It's my pleasure, and it's great to be here in Basel with a group of global physicians.

Alicia Morgans: Yes.

Howard Soule: Trying to figure out what comes next for advanced prostate cancer patients.

Alicia Morgans: Absolutely. It's really exciting here at APCCC 2019. And it's not just clinicians and physicians. There's statisticians, the basic scientist, the nuclear medicine docs are here.

Howard Soule: Yes.

Alicia Morgans: It's really exciting. And you know what? I was just mentioning, before we started filming, I keep hearing the letters PCF. Because you've really had a hand not only in supporting our understanding of the data here at APCCC, where we think about gray data, but in so much of the correlative science and the science that we're discussing here at the meeting.

Howard Soule: Well, it's a pleasure. Our foundation has been funding PSMA science for over 20 years.

Alicia Morgans: Oh my.

Howard Soule: And it is just so wonderful now to be able to double down on PSMA as an imaging agent. We have a long way to go. But the progress is palpable. But to me, even more exciting for patients is the fact that there are now treatments in Phase III trials where PSMA-directed radionuclide therapy really seems to have legs. And we're truly excited about that.

Alicia Morgans: Absolutely. So the VISION trial has come up a number of times here at the conference. And we are not yet debating the data yet, because we don't have the outcomes. But I believe that trial is closed or soon to be closing-

Howard Soule: Soon.

Alicia Morgans: If not yet there. We've tried to enroll patients certainly at Northwestern. But such excitement around that, because it's well-tolerated and looks like it's doing something.

Howard Soule: It really does. We have funded research in Melbourne, in this area, UCLA-

Alicia Morgans: Yes.

Howard Soule: And Weill Cornell. And the three groups have just come together to create a critical mass of new clinical trials for patients.

I'm actually even more excited about the Phase II trials that patients will be able to benefit from today. One in particular that we're funding in Melbourne with Shahneen Sandhu, a medical oncologist, is starting to combine PSMA lutetium with a PARP inhibitor.

Alicia Morgans: Wonderful.

Howard Soule: Another trial combining PSMA lutetium with immunotherapy. So people are really starting to think outside of the box based on strong basic science, good rationale, smart clinical trials. I am encouraged.

Alicia Morgans: Oh, I am too. And I look forward to those moving to our hemisphere at some point too, in the United States. But they are so cutting edge. And I actually commend the PCF for funding the science wherever it's happening around the world, and making sure that those treatments ultimately will find their way to the patient.

Howard Soule: Yes. I think the next exciting wave will come at ESMO.

Alicia Morgans: Yes.

Howard Soule: This ESMO ... So you're too young to remember this, but when you went to ASCO years ago, the prostate cancer session was in one little room.

Alicia Morgans: Yes.

Howard Soule: And maybe 30, 40, 50 people came. And you knew them all. Now we have plenaries at ESMO, at least two that I know of, maybe more. I don't know. But we're looking forward to hearing about the data from the AstraZeneca Olaparib trial.

Alicia Morgans: PROfound.

Howard Soule: PROfound.

Alicia Morgans: Yes.

Howard Soule: They put a press release out so it's not confidential.

Alicia Morgans: Yes.

Howard Soule: The trial was positive-

Alicia Morgans: Yes.

Howard Soule: Which means a survival endpoint was met. We look forward to seeing the data in Barcelona in a few weeks.

Alicia Morgans: Yes.

Howard Soule: That's another one. Our fingerprints, our foundation, actually funded the discovery of the biomarkers that helped to direct that clinical trial. And some of the early science by Karen Knudsen and Maha Hussain on PARP inhibition in general in patients.

Alicia Morgans: Yes.

Howard Soule: So yeah, that's another one. Patients will have more and more options, and that's a very good thing.

Alicia Morgans: Absolutely.

Howard Soule: But you know, Alicia, the trial that I'm really interested in is the one where we're funding the correlates to your darolutamide trial with Dr. Chuck Ryan, Dr. Ryan. You know, the survivorship has been a topic that we have embraced and endorsed since I first met Matthew Smith when he was a fellow with Phil Kantoff at the Dana-Farber. And the outcomes of patients depend so much on physicians that take care of the whole person, not just bombard their cancer with medicines. So the fact that you are a leader in the field now makes us very proud because we seated you and now you have a cooperative group trial, which is fantastic. So I could actually interview you about that trial, but let's just say that patients with neurocognitive defects, those side effects of medications used to treat prostate cancer will be better understood for the work you're doing.

Alicia Morgans: Thank you for saying that. And I think we are so grateful. As an oncologist, as someone who loves people with prostate cancer and who certainly takes care of them in my clinic, it is really heartening to know that the PCF values that quality of life and survivorship experience and makes it a priority. And so just very grateful that you're doing that. And we are going to dig very much into the cognitive function of these men and actually into understanding the biology because part of the problem with things that are less measurable in blood for example, or less biopsy-able, is that people don't necessarily understand what they can't see in a clear way on a figure or a slide or something like that. And so we are going to try to dig into the biology and it's the PCF that's actually funding that work beyond the clinical trial piece. So thank you.

Howard Soule: Everybody that I talked to about that trial gives a very high mark.

Alicia Morgans: Well thank you very much.

Howard Soule: Even the hardcores, you know, it's really good to see that coming along. I would say the other thing, the last point I'd like to make is that we've sort of been an overlooked indication for immunotherapy. Great advances in melanoma, lung cancer, bladder, renal, et cetera, lymphoma, prostate cancer was sort of left behind, considered a cold tumor. I don't believe any of that. And we are funding some very out of the box things to help us resolve the issue of patient responses to medications like PD1 inhibitors, CTLA4 inhibitors, et cetera. So one of the most interesting ones that we're really proud of is an investigation of an inhibitor to IL23 which is an approved drug for psoriasis and the work of Johann de Bono at the Marsden and his colleague just over the border in Italy from where we're sitting right now, Andrea Alamante showed that IL23 and the whole myeloid suppressor component that moves into prostate cancer can be inhibited by blocking this skin T-cell antibody.

It's just amazing. So it's re-purposing an FDA approved drug. That clinical trial is in its very late stages of activation at the Marsden. So that's one part of immunotherapy. Another part is supporting correlative studies around CDK12, PARP inhibition, MSI-high tumors. Trying to find a way to put this all together so that you know, each one represents a small number of patients, but when you add them up, now we're getting up around 10, 12, 14%. So I'm very optimistic about immunotherapy in the near future and the clinicals, the clinical correlative studies that we're funding, Royal Marsden, University of Michigan and other places. Chuck Drake now at Columbia University, IL8, another myeloid suppressor target. This is going to make immunotherapy work, I hope.

Alicia Morgans: Yes. Well, wonderful. You know, I have loved thinking through some of the new areas of hope with you here and I've loved seeing the presentations at APCCC 2019. If you had to sum it up in one statement just to the listeners so they understand how the PCF is thinking about this global change, what would it be?

Howard Soule: Based on this conference?

Alicia Morgans: On this conference.

Howard Soule: So the beauty of this conference, for me being a scientist and not a clinician, although I know pretty much a lot about prostate cancer, oncology, medical oncology, I come to this conference to listen, to talk to people and to understand where the gaps are. What are we missing? For example, PSMA PET. Now it was my opinion, we need clinical trials, but I had no idea that it was proliferating in Europe to the degree it is in the absence of good clinical trials.

Alicia Morgans: Yeah.

Howard Soule: That's just one example of many. How to use the new drugs, how to sequence the new drugs. You know, we can't go another decade without answering these questions and what this conference does, it's so well organized to achieve this point, is that it really lays out not what we know, but what we don't know. And that's important.

Alicia Morgans: Absolutely. We have to start from somewhere and this conference puts us all on that level playing field so we see the holes.

Howard Soule: One other unique thing about the conference this year, and I don't know if Silke remembers, but this is a global conference. Not every physician, and certainly not every patient has the benefit of going to Northwestern University, or Sloan Kettering or MD Anderson. A lot of the attendees at this meeting are from developing nations where their healthcare systems are really resource-limited. So understanding and actually having a whole session on healthcare disparity.

Alicia Morgans: Yes.

Howard Soule: In getting certain presenters completely out of their comfort zone. I mean, speakers like Ros Eeles, she does this kind of research so well at the highest level. She's a real player in the field. But having Dr. Logothetis give a talk on healthcare disparity, you can't buy that at ASCO/AACR.

Alicia Morgans: Agreed. And like he said, it allows someone who's not in it with blinders on to really take a broader view and say, "I'm learning from this and here's what I've found that's new." It really, I think, is enlightening in a whole different way.

Howard Soule: Yes.

Alicia Morgans: Yeah. So thank you so much for sharing your insights and your time. We appreciate it.

Howard Soule: Always a pleasure. Thank you.

Alicia Morgans: Thank you.