Charles Ryan: Hello from PCF 2019. I'm delighted to be joined by the leadership of the Prostate Cancer Clinical Trials Consortium, a group that has helped to develop enumerable trials and therapies for advanced prostate cancer. To my left is Howard Scher, Chairman of the Scientific Oversight Committee of the Prostate Cancer Clinical Trials Consortium. Jake Vinson, he's the CEO, and Michael Morris is the medical director. They all work out of Memorial Sloan Kettering in New York. Thank you for joining me. Howard, give us a little bit of a history on how the consortium came to be, and why.

Howard Scher: Well, the consortium essentially came to be because it was a large investment in research in the early 90s by the Prostate Cancer Foundation, and at that point in time there was really no standards on how to do clinical trials. All of us were trying to do individual site type studies, which would accrue slowly, and we really weren't getting the answers that we needed faster. Also, as physicians, we were spending a considerable amount of time on the bureaucracy that's associated with not only writing a trial, but actually getting it approved. There's contracting. Things that we never learned about in medical school and really shouldn't be spending our time on.

So, the prostate cancer started to come together as a community in the 90s as there were becoming more options and we were learning more about the disease in order to standardize the methods of how we would conduct clinical trials, and start to understand how we would collect the data. It was really the foresight of the Prostate Cancer Foundation and the Department of Defense to put out an RFA to bring sites together in order to collaborate, in order to bring needed drugs to patients faster. We had a particular interest in this area about developing this type of group, and again, with the support for the infrastructure we were able to eliminate a lot of the time and effort that goes into the mechanics of the trials, so we can focus on the science and the standardization.

So in 2005 we launched, and I still remember about 10 of us sitting around a table and saying, "Now that we have this group together, we're starting with eight sites, all of whom had major scientific programs." We've started to come together on how we would standardize how we do trials, and again, not only did this enable patients to have access to the trials in multiple centers, but it allowed each center's research agenda to be done more quickly. Also, it gave you an internal review process so that we could get our ideas vetted more quickly. I would argue that if there was no support for your study or no one had an interest in working with you, that you should probably rethink it. Then things essentially took off very quickly. One of our, I think, poster child, if you will, was this develop of enzalutamide, which started just about the time that we were beginning to consortium. Ultimately that came through as one of the fastest approvals that's been seen in this disease for patients with castrate surgery resistant disease.

Charles Ryan: Right. So for patients who are trying to understand what the consortium does, they should understand that at that time when enzalutamide, and abiraterone was a similar story, was in early-stage clinical trials. A site in California, and a site in New York, and a site in Texas could be doing the same clinical trial with exactly the same set of rules and pooling all of their data, and thus accelerating it times three.

Howard Scher: Correct.

Charles Ryan: So, that was 2005, 2008, Jake. Tell us about the scope of the consortium now.

Jake Vinson: So, with the foresight of PCF and the scientific leadership of that core group of individual members, the organization has flourished. There's been over 300 clinical trials run through the prostate consortium at this point. Over 9,000 men enrolled to those studies. We've expanded the scope at this point. We have 70 plus sites and have a reach into 13 countries now. So, we've really been able to facilitate an infrastructure that can accommodate any type of research project that our clinical scientists want to pursue. We really feel like we've gained the stability from a financial perspective to have the business side of it run very efficiently, partnering with pharma and biotech companies all over the world now to have access to what we think might be the best, most cutting edge drugs and biomarkers to really make a difference for men with prostate cancer.

Charles Ryan: That's a key point that you made. I think you said 70 sites or something like that. Which means that it's not just a core group of eight sites that have a high, high volume of prostate cancer. It's smaller sites that have an interest in being part of a bigger network, and they're able to join. Mike, tell us about the challenges you see facing the consortium in terms of the scope of the work that's being done scientifically, medically, across 70 different sites. I know you've got an effort that's international now as well.

Michael Morris: Yeah. I mean, I think that the depth, breadth, and scope of the trials that we're doing now are not so much challenges but advantages. I think the big challenges that we face are from a logistics standpoint, which Jake and his staff have really expertly navigated, but I think that from a standpoint of a patient, just think. 10 years ago, a patient would need to get on a plane and seek individual second opinions. Maybe there was a center that specialized in a specific therapy in one place, and then they'd fly across the country to get to another place that maybe had something also that was novel. Now with all of these centers and a burgeoning international presence, just like Howard was saying, it amplifies each investigator's scientific interest. Well, it disseminates that to allow for patient access.

So yeah, it provides logistical challenges to manage that. The advantages are so overwhelming for both patients and scientists alike to have that increased access of care to patients who really do want to participate in trials, but before just from either geographic or financial issues, couldn't access a novel trial of a new drug that they have perhaps read about and now can access that. Without a significant amount of travel or relocating to someplace else. It's a huge advantage and something that I think that makes all the challenges of expanding like this over the last decade well worth it.

Charles Ryan: So for those who are new to thinking about this, tell us what's the difference, Howard, between the consortium and a pharmaceutical company running a clinical trial? How do they differ?

Howard Scher: I mean, it's really as a collaboration. The beauty, one of the strengths of the consortium is that we are constantly learning more about the disease from our colleagues in the laboratory. We can take those endpoints, if you will, and targets, and develop the trials. So that is a very strong effort. We start with scientific discovery, we prioritize targets for treatment. We've also had a major collaboration with the FDA working to develop new endpoints for clinical trials so drugs can be made available much more quickly. Doctor Morris, in particular, has focused on an endpoint, which was validated as a, "biomarker," where he was able to show that if you looked at how progression of disease measured reproducibly and accurately, is a surrogate for survival, and now that is a regulatory endpoint so you don't have to wait until you see this arrival endpoint in order to enable it to be approved.

Charles Ryan: So, the standards or the rules by which we judge the success or failure of a therapy now, whether it be in clinical trials or even in standard of care to some degree, has been defined by this group to large extent through cooperation with entities like the FDA. Actually taking multiple different sponsors for clinical trials, forcing the same rule book if you will, create standardization across the field.

Howard Scher: For a sponsor, you can look at it as one-stop shopping. So, we collaborate with pharma. We know their preclinical development groups. The more that we understand the underlying science behind a particular target and drug, we actually start working with it in our laboratories before it reaches the clinic, so we know specifically how to tailor that trial to show that if it's a targeted agent, it's hitting the target. It can shorten the timelines until you understand how best to administer it safely for optimum efficacy. Then the trials can go on very smoothly. To do these one at a time takes an enormous cost, an enormous amount of effort. We essentially meet every time if there is a meeting on prostate cancer. We have monthly phone calls. We vet things with a very short summary, and that's enabled the group to be so successful.

Charles Ryan: It's been successful and now it's actually branching out of prostate cancer. There are other consortia that are forming, tapping into your knowledge and experience to try to develop similar models in other diseases.

Jake Vinson: Yeah. So, we've been very collaborative with other therapeutic areas. We've collaborated with the GI groups, lung groups, brain cancer consortium, and then most interestingly with the Veterans Administration. The Prostate Cancer Foundation has made an investment in key centers that have VA Hospital presence, to make centers of excellence. So, we're closely collaborating on infrastructure development for them to find efficiencies in developing their clinical research portfolios, making the drug, and biotech company connections to be able to support those studies. Then to bring quality clinical research to veterans as well. It's pretty exciting stuff.

Charles Ryan: Great. So Mike, this consortium has largely been a Phase I, Phase II entity. You're the PI of the first Phase III study that's being done through the consortium. What was involved in taking that leap, and is that going to be the new normal?

Michael Morris: Well for Phase III trials, I think there are multiple models that work. There's a place for the consortium, a place for the cooperative groups, a place for industry, but I think that what we have brought to the Phase III arena is that same level of expertise and consistency, and working on an international basis. Because part of that Phase III, this is the DORA trial, which is docetaxel and radium versus docetaxel alone, is that we can then bring the experts both in the US and in Europe to bring to bear and deliver to industry a trial that is done by the top prostate cancer investigators over the world.

I would say that not every Phase III needs to be done through the consortium, but there is a place for a Phase III in which you really do need specific expertise brought to bear, especially in Phase IIIs that we're trying to build a lot of biomarkers around. There is nothing like a good Phase III with a clinical endpoint to validate your biomarkers. Industry isn't necessarily the best vehicle for that, but what we can do to bring in into a Phase III that the consortium, is experts in both tissue, liquid-based, and imaging biomarkers, build it into the trial so that whether the trial is positive or negative, we learn something as a field that we wouldn't have done otherwise. I would say that our Phase III is a marriage between academia and industry, and that's really the ideal model where we bring the science, they fund the clinical aspects of the study, and at the end of the day we have a much more informative Phase III study than most Phase IIIs that are done.

Charles Ryan: Well I'll say for my own part, I've been involved in the consortium since I was a very junior investigator. I would say that I'm a pretty good example of somebody who's benefited from that participation, at my prior institution and at my current institution. I think that one of the things that I'll say, because it wasn't said yet, is it's also a great way for people to launch their careers who are maybe at centers that don't have the high volumes that used to be needed for getting these types of trials done. Integrating translational science into the clinic. So that's another piece that's really important. I'm just amazed that we're sitting here talking about 70 centers now participating in the Prostate Cancer Clinical Trials Consortium. It's a tremendous legacy for all three of you and the work that you've done, and of course all of that on behalf of prostate cancer patients. Maybe other cancer patients as we serve as a model for how to develop new therapies in this disease. So, thank you all for joining me. Really informative, and thank you for all your hard work in the consortium.

Howard Scher: Thank you.

Jake Vinson: Thanks, Chuck.

Michael Morris: Thanks for having us.