Rich McCormick: Hi, I’m Rich McCormick, Vice President of Oncology at Vial. Vial is a next generation tech-enabled CRO that delivers faster and meaningful cheaper trials through an end-to-end technology platform. Today I have the pleasure being joined by Dr. Nathan Pennell from the Cleveland Clinic. Welcome Dr. Pennell.
Would you like to give an introduction?
Dr. Nathan Pennell: Yeah, thanks Rich. Nate Pennell. I’m a medical oncologist specializing in treating lung cancer patients at the Cleveland Clinic Taussig Cancer Institute in Ohio. I’ve also been running clinical trials in patients with lung cancer for most of my career.
Rich McCormick: Great. Awesome. Welcome. Also, knowing that you have a vast experience in working with these oncology trials specifically in lung cancer, can you tell us what treatments are currently available for patients with lung cancer and mesothelioma and what’s lacking in these treatments?
Dr. Nathan Pennell: The, treatment has changed so much over the last 15 years. When I first started my career really everyone with lung cancer and mesothelioma as well really was treated the same way as though it was just one disease. And everyone got chemotherapy. And it worked for some people, but for most people it didn’t. And we didn’t really understand why. And even clinical trials done 15, 20 years ago, every drug was more or less given to everyone, indiscriminately just added to the standard treatment, and hoped that it would work without a whole lot of rational. What’s changed since then is we’ve been able to harness our understanding of the biology of lung cancer and mesothelioma, and now split it out essentially into multiple different diseases that can be identified with things called biomarkers.
That you can do on newly diagnosed patients and now do trials in enriched patients where it’s much more likely the treatment’s gonna work for those patients, which also spares the side effects and the cost to all the people that it’s not likely to benefit. And today what we’ll do for a newly diagnosed lung cancer patient is do a series of genetic and other biomarker tests, and then they’ll either get a targeted treatment directed at a particular genetic alteration such as an EGFR mutation, for example.
Or they may get something called immune checkpoint inhibitors with or without chemotherapy based upon something called PD-L1 levels. Essentially everyone has a better chance of getting their cancer under control and living longer than they did 15 years ago. And this is even permeated across different stages of disease.
What’s really lacking despite all of this excitement is one, we’re still not really curing anyone with advanced disease, even though people are potentially living much longer than they used to. And two, we’re still only probably bringing these targeted advancements to somewhere half of people with lung cancer and, mesothelioma.
And so we really need to continue to expand this to get everyone else.
Rich McCormick: Thanks to that information, Dr. Pennell. So you mentioned lung cancer and mesothelioma being split into separate I guess we could say indications. Can you maybe elaborate on mesothelioma and why it’s so difficult to treat?
Dr. Nathan Pennell: Sure. So pleural mesothelioma, which is the most common kind is, tends to be treated by the same doctors that treat lung cancer, but it actually is a cancer that emerges from the lining around the outside of the lung called the pleura rather than the lungs themselves. So it’s very heavily associated with asbestos exposure rather than what most people think of with lung cancer as being associated with tobacco smoke. Mesothelioma is challenging and in many cases considered incurable because really of where it is. So if you think of your lungs as a room, If you have a lung cancer in your room, which is say a chair, you can take the chair out, you can cut out the cancer, and then you can cure it.
But if you think about the mesothelioma being the paint of the room and having to try to remove every last little bit of paint from the walls of the room and ceiling and floor of the room, it’s really almost impossible to physically do that. And despite the fact that there often is not distant spread of mesothelioma and it’s almost impossible to cut it out and cure it.
So we’re stuck with having to give systemic therapy. And traditionally that’s been chemotherapy for patients with mesothelioma. The other thing that has made it very difficult to treat is that it’s quite rare now, which is thankfully because asbestos is no longer used all that much in the last few decades, but we still see probably a few thousand cases in the United States per year.
Probably enough patients at any one time with mesothelioma to have one big major clinical trial going on. And so you have to pick the right one and the right drug and the field just doesn’t move forward as quickly as it does in lung cancer. [00:05:00] The other thing that makes it hard is it’s a very heterogeneous disease and there are different histologies.
Some patients have disease that moves very slowly and in lay over a slow a long period of time. And some people have incredibly aggressive disease and they don’t live very long at all. So you can’t really extrapolate what you learn about some patients with mesothelioma to every patient with mesothelioma.
And then finally it’s a, cancer that tends to strike older individuals who tend to be very ill when they present, which makes it even harder to enroll them to clinical trials. So put that all together and it ends up lagging behind it’s big brother of lung cancer and oftentimes the advances we make in lung cancer later on get applied to what we what we do in mesothelioma.
Rich McCormick: Sure. So we’ve mentioned research a couple times. Could you maybe talk to us a little bit about lung cancer and mesothelioma trials and what makes them so difficult to recruit? What are some of the common challenges you’re seeing in the space.
Dr. Nathan Pennell: Yeah, clinical trial recruitment is a problem that’s not really unique to lung cancer and mesothelioma.
It’s, really a a national problem. We know that probably in the range of 5% to 8% of cancer patients are getting enrolled to clinical trials in the US at any one time, and that certainly is not better in the thoracic cancer space. It’s incredibly disappointing too, considering how much cancer is advancing, and these days clinical trials are so much more rational that patients have a much better chance of responding and benefiting from a clinical trial than they would have a decade or longer ago. Oftentimes patients come in and they aren’t even offered a clinical trial. I think the biggest barrier to a patient being offered a clinical trial or participating in a clinical trial is actually having a clinical trial and it being offered to them.
Many practices are simply not choosing to participate in clinical trials. They’re complex. They take a lot of expense and personnel to open and to maintain. And we know that right now we’re going through one of the biggest challenges in staffing of clinicians, nurses, and that absolutely is applying to clinical research as well.
It’s making it really complicated for sites to participate in clinical trials. It’s much easier just to go ahead and treat someone with standard of care. We also know for physicians who would be offering these trials, they have a lot of pressure on them to see as many patients as possible try to improve their productivity.
And offering clinical trials takes time. It takes much longer to discuss the pluses and benefits and risks of a clinical trial than it does to just offer guideline directed therapy. So right now clinical trials are only being offered by people who really have a passion and believe in the importance of clinical trials, even when clinical trials are available, many places don’t have a good match between the trials they have open and what their are patients they’re seeing, so they, more or less have to guess at what trials they want to open without having a good understanding of what kind of patients that they see. And even if they do have a trial that is matched with the type of cancer, the stage of cancer that they see in front of them, they wanna offer it.
Oftentimes, clinical trials have such restrictive eligibility criteria that only the very minimal disease, healthiest patients are making it on to the trials if. You could read my friend Mikkael Sekeres’ new book called Drugs in the FDA that he just published, he comments that it’s, it takes an Olympic athlete to qualify to get on a clinical trial these days.
And that’s something that we really need to change because more people can benefit from this. So there’s lots of potential in the space to improve this. We have to match our patients better to clinical trials. We have to be able to open and conduct them at more places, not just at big centers that have an academic mission, but everywhere where the patients are seen, and then we actually have to bring it to the patients so they don’t have to travel away from where their, home is. Have to make the trials less complex, less restrictive, and a lot less expensive if we’re gonna bring these advances and trials to more patients.
Rich McCormick: Thank you for that. I love that quote. So Vial works with a lot of small biotech companies. So let’s assume we have a new biotech that has a new oncology treatment and they’re gearing up for their first clinical trial, and they’re looking for you for advice. They have to make key decisions around protocol design. And their selection, CRO selection key sites to work with. What advice would you offer that executive team to help them make those decisions and start on the right track.
Dr. Nathan Pennell: Yeah. There’s a lot to unpack in, in that when you’re working with new companies that are developing drugs, it depends a lot of course on what, phase of development they’re looking at. So if you’re looking for a, say a [00:10:00] first in human phase one, you wanna work with the company about what, based on the biology of their drug, what patients do they think it’s gonna fit best? What sort of cohorts do they wanna open? You wanna make sure that they tailor their trial so that they can prove that it’s effective and that it’s safe. But you also wanna make sure that the trial is not so burdensome, that sites won’t be willing to open it and that it’ll fail because no patients accrue.
You’d be shocked at how many companies have brilliant scientists and incredible drugs and not the slightest bit of understanding of how feasible it is to get a giant hunk of tissue on every patient before they start on their treatment. Clinician coming in can really have a lot of benefit to that early phase of design for later phase studies that are going for FDA indications.
Some of the biggest things that we talk to them about are are you designing your trial in the right space, in the right indication for a major unmet need. Are you picking the right comparator arm for your standard of care arm in a randomized trial? And are you picking the right endpoint that’s gonna lead to an FDA approval?
And so lots of interesting discussions that go on, but of course, many of these sponsors. Companies already have a protocol written and ready to go, and they wanna start opening it. So the more mature companies often have networks, especially of early phase sites that they have good experience with.
They know that they can work well with them. Contracting is easy and they can put lots of patients on, but smaller companies, especially ones that are coming from outside the US and trying to break into the market, don’t necessarily do that. And they really are gonna rely on picking a CRO that has a network of sites that they can work with.
And so it’s really critical that CROs have a good track record of selecting sites to open trials. The amount of investment and time that goes into selection of a site and opening a trial is just so much time and manpower that goes into that. And then if they don’t accrue of any patients, because nobody bothered to check that they had competing studies or that they don’t have the personnel available at that time to actually put someone on, and suddenly you’ve wasted all those resources and trials fail because they don’t accrue in an appropriate period of time. The other thing, of course, is when you’re working with them about picking CROs, is you want CROs that have a good reputation working with sites. Sites, believe it or not, keep lists of CROs that they don’t wanna work with and when you start to do what’s called a feasibility analysis for a new study, that comes up.
And if you’re like, hey, this CRO we had a lot of difficulty with, they take three times more of our personnel’s time answering queries and trying to figure out adverse event reporting. And their monitors are really hard to work with. And we choose not to participate sometimes based on that. Lots of ways that CROs can work with sites to make things a lot more smooth, you can ensure obviously that your data is, has high quality and is well monitored and, being conducted appropriately while also minimizing the burdens on site. So that’s something that I think needs to improve dramatically going forward.
Rich McCormick: Yeah, that your response really hits home in terms of Vial’s mission. So two of the things that you mentioned one has to do with the site, the sites that are being selected for these studies. So we are currently expanding our, early phase oncology network to allow clients quicker access to, like you mentioned, like contracting, feasibility information. And then the second piece, the inefficiencies. So our technology platform that we’ve developed and are actively using is meant to make these trials more efficient, not just for the sponsor, but mainly for the sites. So that they’re able to get through get through the trial quicker than than we’ve seen before.
So a question for you, looking into the future, 10, 15 years down the road. How do you see the space evolving and, technology’s involvement being a significant role in that?
Dr. Nathan Pennell: Yeah, it’s actually frustrating to conduct clinical research, knowing what potential there is for technology in other areas of our lives that seems to work so well.
Right now, to find a patient for a clinical trial, it’s almost completely analog and completely up to individual people thinking of what trials they wanna open. Thinking to match a patient that they’re seeing with a trial that they may or may not have open at that time. Thinking about that they might be eligible, but not really knowing that for sure.
And then having to put them through protracted screening processes, which they may fail or maybe not even understand it well enough. And then the, to explain it to the patients that they should participate. We have these, Wonderful electronic medical record systems, which as much as we complain about them, are so much better [00:15:00] than they used to be. And they have such untapped potential and so much data. If they could more efficiently tell the investigators what patient populations they have so that they know what trials they need to open, if they could integrate trial data into the EMR so that some software was able to somehow pre-screen patients and pull out, say, “Look, I’m seeing this patient today.”
This trial is available to them and I’ve already looked through all of their eligibility criteria based on what’s there and they likely are available. Once you open the trial, if the technology was able to pull out their staging, their pathology, their genomic data to match them to a study, and then even when they’re on trial, be able to pull like efficacy data from their scan reports, toxicity data from the notes and from the labs and whatnot. You could essentially, seamlessly run the trial and it would make monitoring really easy, there would be fewer deviations and it would allow us then to also open studies and provide them to people that currently can’t participate in trials.
Sites that right now just feel like they don’t have the resources. It’s too much time, too much investment or, patients that are in rural areas that don’t wanna drive to some place where there’s a major academic center. You can imagine patients, let’s say in rural West Virginia, who might want to drive four hours to see me, but just can’t do that for their standard treatment.
Could get a biopsy locally that could get plugged into, let’s say a genomic testing provider that could immediately plug into some sort of national system that would alert their provider that there were three trials available that were a perfect fit for this patient. They’d already integrated with the patient’s EMR, looked and said that they likely are eligible, and then they could immediately open that trial.
Using something like a just in time mechanism where the trial could open within a few weeks. Everything could have been pre-done ahead of time. They could ship smart technology to the patient at home where they could plug in to monitor their vitals. They could do their visits over virtual Zoom something like this, or use smart devices to record PROs and other things.
We could ship them the drugs which could have a smart bottle that could tell whether they were compliantly taking it, all of their scans could be done with their local doctors. This is already exists. The ability to do this. We just can’t because everything is still so stuck in the 20th century and how we practice medicine..
Rich McCormick: Yeah that’s a great answer. And, just to make you aware, Vial currently has access to over 75 EMRs at this point. So we’re growing our ability to do exactly like you said, to be able to find those patients and connect them with trials.
Dr. Pennell, thank you so much for your time today. We look forward to working with you in the future.
