The Caris Precision Oncology Alliance™ - Chadi Nabhan

January 4, 2023

Chadi Nabhan joins Charles Ryan to discuss The Caris Precision Oncology Alliance™ (POA), which focuses on precision oncology to optimize clinical care and outcomes of patients with cancer. The Precision Oncology Alliance gathers real-world data from patients that undergo molecular tumor profiling across the spectrum of solid malignancies and feeds the data into a large database that can be accessed with clinical outcomes. The Caris Precision Oncology Alliance provides access to this data to Precision Oncology Alliance investigators and institutions, to identify predictive and prognostic markers to further advance the integration of molecular profiling into all aspects of cancer care and to identify therapy options and clinical trial opportunities based on the unique molecular characteristics of a patient’s tumor.


Chadi Nabhan, MD, MBA, FACP, Chairman, Precision Oncology Alliance, Caris Life Sciences

Charles J. Ryan, MD, the President and Chief Executive Officer of The Prostate Cancer Foundation (PCF).

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Charles Ryan: Hello from San Francisco, we are at ASCO GU 2022. Great to be back here in San Francisco. I'm delighted to be joined by Chadi Nabhan, who is the Chairman of The Precision Oncology Alliance, which is within Caris Life Sciences. Chadi, thank you so much for joining us.

Chadi Nabhan: Chuck, thank you so much. It's so good to be here in person, and back again.

Charles Ryan: Yes, it's great to be back. Before I joined PCF, I was working with you, we were working quite a bit on the Precision Oncology Alliance and we were leading the GU Program within that Alliance. I was really impressed by what we were doing, there are a lot of people getting involved. I think the world should know a little bit about this. So tell us about this program that you have and some of the results you are seeing.

Chadi Nabhan: So, really the Precision Oncology Alliance is a research enterprise within Caris Life Sciences, and really that research entity relies on collaboration between Caris Life Sciences and the scientific platform that we have, and academic centers and healthcare systems across the country and around the globe. This collaboration between all of these sites and Caris Life Sciences relies on the data capability that we have of molecularly profiled patients linked with outcomes. So we really designed the Alliance in a way that we try to ask pragmatic questions across various disease groups, not just GU. GU, GI, breast, GYN, all of these disease groups. These pragmatic questions, hopefully, could have an output that is relevant to how we care for patients. So you've been involved in the GU group and pretty much the Precision Oncology Alliance GU group is going to meet actually today.  We are taping this on Thursday and we have research projects that we really produce over the year, and we are very happy to present several of them during this meeting.

Charles Ryan: So, just for those who aren't familiar too much with Caris, you are taking the community to acquire... samples that are taken from biopsies, prostates, organ biopsies, genomic sequencing, you do that as part of your commercial enterprise, but the data is being fed into a larger database that can be accessed with clinical outcomes. And that's sort of the key unique facet of this. Have I pretty much got that, right?

Chadi Nabhan: Yeah. So really the uniqueness of this is... think of it as real-world data. I think we all can agree that real-world information differs vastly from what happens in clinical trials. So what we wanted to do is try to better understand what happens in the real world and research that in a pragmatic way. So we have real-world data from patients that undergo molecular profiling for clinically approved indications across the country. These molecular profiled data are linked to outcomes and all of the information is de-identified. So there is no PHI, there is no identifiable information. And we provide access to this data to Precision Oncology Alliance investigators and institutions, to answer or to ask questions that we can answer. The data that we have are available for research. We believe conceptually in data democratization, because if you really don't take advantage of the data and make use of it to help patients who are unfortunately diagnosed with cancer, what is the use for that. So that is really what we try to do, and as I've told you, we do that across the spectrum of solid malignancies.

Charles Ryan: So let's talk about some of the examples of the data that's been generated through the POA. I was on a few abstracts last year, I think I'm on a few this year as well. And what's been really fun is we can generate questions around the prevalence and the frequency and the associated outcomes of various mutations and things like that. So tell us if you will, let's start with prostate, just a couple of the abstracts that are here. We can just talk in broad strokes about what type of data you are presenting.

Chadi Nabhan: I think to back up just a little bit, I think one of the nice things about data like this is you can start asking questions about rare tumors and rare cancers. Because we have a lot of data now and in clinical trials, some of these are very difficult. So currently we stand at 275,000 molecularly profiled patients linked with outcomes, so we can start to mine that data and ask rare questions. One of the abstracts actually that is being presented at the ASCO GU meeting this year is by Dr. Nazha. And it's really talking about penile cancers. These are very rare tumors, in fact, we are probably reporting on the largest series, about a hundred plus, about 108 patients.

And the question was if we take these cancers, can we actually differentiate between the subset that is linked to HPV positivity and the others that are HPV negative. Is there really a difference in the molecular signature, between squamous cell carcinoma of penile cancers, or HPV positive versus HPV negative? And maybe by exploring this, we will have some therapeutic implications.  And, sure enough, we are actually... I do identify different signatures and hopefully, this has therapeutic applications. And this abstract is going to be an oral presentation.

Charles Ryan: Congratulations, that's great.

Chadi Nabhan: Yeah. Congratulations to the authors and to the folks who really came up with the idea. Another thing that we are looking at is an abstract that is led by Dr. Rana McKay from UCSD. And she really has the idea of looking at renal cell carcinoma, metastatic disease, and trying to identify molecular signatures between primary tumors and metastatic disease. But more importantly, whether the site of metastasis has also a different signature, as you know some renal cell cancers that have a different site of metastases but have a different survival than the other. So, these are things that are very difficult to do in randomized controlled trials, but they are important and they ask important questions so we are very happy to do that. And I'm very delighted to see your role, and really, congratulations on everything that the PCF is doing, it is really amazing.

And in the Precision Oncology Alliance, in the GU group, we are really looking forward to finding opportunities to work with PCF, because we have a common vision. Your vision is to find these opportunities to hopefully fund researchers that are really asking questions to help patients. And our vision is, we want to provide the data to answer these questions. So we are both rowing in the same direction. So I'm very excited about this, and I'm really looking forward to finding that, what can we do together to help patients?

Charles Ryan: Yeah, I appreciate you saying that.  Our vision at the PCF now is that we can broaden our scope in the battle against prostate cancer, by education, communication, funding research, and helping patients a little bit more directly than we have in the past. And one of the ways that we want to do this, is we want to communicate to patients that we want them to know what is going on with the genomic sequencing of their tumor, as they are getting therapy and when therapeutic questions arise between them and their clinician.

And so the understanding that these data are being used to identify patterns across the country, to identify subgroups of prostate cancer and other cancers, is I think tremendously valuable. And I think to your point about the democratization of data, you are doing something that we can help encourage in the PCF, which is that the acquisition of this data, the use of this data not only helps you, the individual patient who is having genomic sequencing performed, and helps you and your clinician, but you are also feeding into the greater whole. And, that is something that is a big part of what we would like to do, to end this suffering and death from prostate cancer over time, which is really our mission at the PCF.

Chadi Nabhan: Absolutely. And one of the things that you learn when you look at these real-world data, is you see the differences across tumors and who undergoes sequencing and who doesn't. So to your point, about prostate cancer in our dataset, we have just a little bit, about over 7,000 patients with prostate cancer that have undergone molecular sequencing, while in non-small cell lung cancers, we have 47,000 and so on. So when you think about this, maybe it should be in the middle, and there are probably opportunities to really better understand who should undergo genomic sequencing? Why? And then what do you do with the information? And short of really doing this together is impossible. And as we always say it, Chuck, "It takes a village." And we can't do it alone. The Precision Oncology Alliance literally was formed because simply we need the collaboration, we need to work together and the PCF also feels the same. So I think we could do a lot of good things together.

Charles Ryan: Me too, and I just want to make one final point about that village. This is another huge part of what we do at the PCF, as we try to cultivate junior investigators, young investigators, we have a very strong Young Investigator Award Program, where we take people who are just coming out of their postdocs, they are coming out of their fellowships, and we are showing them that a career in prostate cancer is meaningful. There is a great community, there's great science. And hopefully, we can say that the POA is one avenue through which our young investigators can acquire data that they can analyze.

Chadi Nabhan: Absolutely. I can tell you, as the Chairman of the Precision Oncology Alliance, one of the things I really love the most is when there is a fellow or a junior faculty who is presenting at one of our meetings, an idea, a concept, a question, and we are there to provide the support for that investigator. We've all been junior investigators at some point in our lives, and we always were trying just to find a project or two that we can dabble within research, but hopefully meaningful. And that is what we try to do, we want to really diversify the ability of investigators to get in. And our goal is to support these young investigators who are hungry, who want to make a difference.

And we want to be a part of their journey. And another abstract, we talked about the penile cancer one, the kidney cancer one... But I'd love to mention also to your viewers and to your listeners, the one we did last year, actually you probably led this Chuck. I don't know if you remember or not, but you were very influential in it. And you looked at the ATM mutant prostate cancer tumors and tried to understand the prognostic significance of that. And the most interesting part of your abstract last year, Chuck, what I found is that it really did have a therapeutic implication to it. And I think that's really what I love to see and what we all want to see.

Charles Ryan: We did this analysis because we saw that patients with ATM mutations, weren't responding to PARP inhibitors. And we said, "Well, how does the rest of the genomic profile look in ATM mutated prostate cancer compared to BRCA1 and BRCA2?" And what we found, is that they were very different. And the co-occurrence, for example, of TP53 alterations, was very different in the ATM mutant group versus the BRCA1 and BRCA2. So they're just independent of the DNA repair aspect of things. ATM mutations tend to travel in a higher mutation, a higher risk prostate cancer cohort if you will. So that could not have been done by a single center. It had to be done... we did it really quickly, in other words. And we were able to pull data from all the community sites and we had a nice abstract for what is essentially a rare mutation within the process.

Chadi Nabhan: That is really the value of collaboration. And one of the most valuable things that I'd like to mention again is, whenever you look at these rare mutations, I mean, ATM is not that common in prostate cancer you need large samples to be able to answer a question that is going to mean...and what's important about this, it may not be that common when you look at all prostate cancer patients diagnosed in a given year, but for that one patient that has that one mutation, it is 100%.

Charles Ryan: 100% exactly.

Chadi Nabhan: And that's what matters.

Charles Ryan: Well, congratulations on all the results that you are presenting at ASCO GU this year, I know there will be other abstracts coming up at other meetings. So it's good to see the Precision Oncology Alliance in full force and moving forward. And yes, I look forward to working together with PCF and Caris in the future. Thank you for your time today, Chadi.

Chadi Nabhan: Thank you, Chuck. Congratulations, looking forward to working with you.

Charles Ryan: Thank you.