Scientific Leader Spotlight: Ari VanderWalde

The People of George Clinical

Profiles in Passion

Nothing defines the unique character of George Clinical more than the people who do the important work of researching treatments and clinical practices that will shape medical policies and practices in every corner of the world. While our Scientific Leadership Team members are a diverse group from many countries and therapeutic areas, one thing they all share is a passion for making an impact on the treatment, and thus the lives, of the patients they serve. These are their stories.

Ari VanderWalde, MD, MPh, MBioeth, FACP

Dr. VanderWalde is the Vice Chair of the Precision Oncology Alliance as well as the Global Chair of Clinical Trials at Caris Life Sciences. An internationally recognized cancer researcher, Dr. VanderWalde was previously the Director of Research at West Cancer Center and Research Institute in Memphis, TN, where he is still a member of the research faculty. He held a dual appointment with the University of Tennessee Health Science Center as Associate Vice Chancellor of Clinical Research and Associate Professor in Hematology/Oncology. He has been a Senior Medical Director at George Clinical since 2014. His primary research has been in melanoma, immunotherapy and targeted therapy including combinations of therapy and mechanisms of resistance.

What inspired you to have a medical career and more specifically to focus on oncology?

Everybody expects there to be an aha moment when you when you figure out what you want to do with your life. I’m not sure I had that moment, but I definitely had some inspirations. My dad is a pediatrician, and growing up we lived in a pretty tight community. On Saturdays, people would knock on the door, saying—my kid has an earache or stomachache or something like that. My dad would stop whatever he was doing and tend to whatever it was, so they didn’t have to go to urgent care or the emergency room. And I always remembered that—that my dad being a doctor wasn’t just something that he put down at the end of the day—it was something that was more infused in him. And that’s who he is even now at 75 and still in practice. I always admired that in him.

Why oncology? From the start I’ve always had one foot in science and one foot in patient care—and I’ve moved between those two since I was in medical school. I did a fellowship in oncology, got a degree in biomedical ethics and even a master’s in public health. And when I had to make a choice during my residency between primary care doctor or specialist, I wanted the more exciting path—a way to actually make a difference for patients. Listening to the attending physicians speak to patients about cancer, the idea of care just became really exciting for me, and it’s something that has kept its excitement throughout my career. And from the science point of view, if I hadn’t gone into oncology, I wouldn’t have been at the forefront of some of these amazing discoveries that have been made over the last 10–15 years. So, I’m really glad I made the decision.

You’ve treated cancer patients, done clinical research, been in academic settings, worked with big pharma—done it all. How has this broad exposure shaped your viewpoint?

There are definitely a lot of different ways to approach cancer. A lot of physicians and scientists don’t know much about the patients—they just hate cancer. And there are some doctors who love the patients but don’t really understand what happens in terms of cancer—they just know the drugs that work. As a scientist—a researcher—it would be easy to take the “I hate cancer” approach and not think about patients. But if you take care of patients with cancer, it teaches you that cancer doesn’t fit into a box—that people don’t fit into a box—that every person has a different journey and different priorities in terms of what they need—that it’s not as simple as giving them a drug to extend their life or make them feel better. You see the unfortunate side effects that many cancer treatments can have, and you try to calculate the risk and benefit ratio for all the therapies you use. Although scientists working in the lab with mice are the ones who have made all the major advances for cancer therapy, they don’t get this perspective.

Having a foot in both worlds has made me both a better scientist and a better physician. I think it’s important that my research career really started with looking into the patient experience. In my early days as a fellow at City of Hope, I focused on older adults with cancer—determining whether or not they were able to tolerate therapy. I think that was a good entryway into research—to be thinking about it from the patient’s perspective first and from the scientific perspective after.

So, with whatever I do, I need to be in the space where the patients and the science meet. And that can shift your outlook. For example, patients are not “cancer patients”— they are people who happen to have cancer. And neither having cancer nor being a patient defines them. I’ve focused on clinical research, which is the intersection of what happens to patients with new therapies or with new interventions. It’s based on what the individual patient is experiencing. Clinical research tells you that a drug that looks like it’s really good at killing cancer can also kill the patient. And it’s no good to be able to heal the body if you can’t also spare the soul.

You have spoken in the past about the process of clinical research in oncology—saying it is a labor of love that requires “stick-to-itiveness,” focus on one question at a time and real training. Having worked with big pharma can you speak to the process of taking a drug to approval—the pathways and challenges?

Rather than focus on the hardest part of drug development,which is in the lab and is basically a lottery, I’ll focus on the drugs that actually get into patients. Safety is really the most important thing that we end up defining. It’s also the most important thing—the thing that regulatory groups like the FDA end up looking at—and if it’s not approved by the FDA, you can’t give it to patients. So, safety is the biggest first step of drug development. 

After we demonstrate an acceptable level of safety, which is its own science, we move into phase II trials with a larger group of patients and start looking at whether the drug is efficacious—actually works. And that’s hard to do. We’re still looking at safety and getting a broader sense of possible side effects. This is also where we see whether or not it’s worthwhile to go to a very broad group of patients. Clinical research can cost up to half a billion dollars, so we need a signal to continue forward.

The end piece is the phase III trial—the registrational trial—that compares the active agent or drug to either the best available second drug or to placebo if there’s nothing that is standard for those patients in that stage of their cancer. The purpose is to be able to demonstrate efficacy good enough to convince the regulators to approve that drug, and that is difficult. It’s expensive—costs of clinics, CROs, pre-filing and regulatory submissions, all the internal monitoring—and you’re going through this complicated process while you’re also racing two clocks.

The most important clock is this—for every minute it takes to get the drug that is showing it works onto the market, lives may be lost and cancers may have grown. In addition, the clock is racing because the patent on that drug expires at some point, and the drug company wants to move quickly. But you want to do things right—make sure you get meaningful endpoints that will determine whether or not the drug really works—is effective. It’s a real challenge. The hardest part of doing clinical research is the clinical research. One piece is not harder than the next. But making realistic timelines and sticking to them is extremely important.

How important is it in this complex process to have scientific leaders involved throughout the entire trial?

For every phase of a clinical trial, you need to have a doctor who takes care of patients with cancer actually looking at that trial. The drug company knows the drug better than anybody else in the world. They know if it’s going to work—they know why it should work. They do have doctors in the drug companies who are able to look at it, but it’s not the same as having a physician who is an expert in the cancer that is being treated to look at the protocol asking if the drug does what it needs to do for patients, and is it going to actually accrue patients in a timely manner.

It’s very important and something that George Clinical really excels at—making sure that there’s a physician who looks at all of the protocols and is giving guidance. They ask the right questions along the way. What are they trying to do? Are they actually going to do it? Are they asking too many questions to get important answers, or are they asking one question they can get a definitive answer for? So having a clinical trialist who’s done this before—is a physician who has treated cancer patients and also has the perspective of a CRO to say if they can actually accrue the trial in the timeframe that is expected—is a real value that George Clinical brings.

Give me a synopsis of what we’re going to see in cancer care in the next 5–10 years.

We’re going to start seeing more targeted therapy and also more immune therapy, which is recognizing that cancer is able to grow because it’s able to hide from the immune system. What we’ve developed in the last 10–15 years is a variety of different ways to be able to show the immune system—“Hey, look, there’s cancer here, you should start attacking it again”—and that’s been extremely effective. And there are alterations in cancer that actually can tell you whether immune therapy is more likely to work or not likely to work, just as it can be for targeted therapy.

We’re beginning to see new immune therapies that can be used in cancers that have not been that responsive to those we currently have. Those cancers are the ones we’re really going to find out about in the next few years. We’re also looking at tumor infiltrating lymphocytes (TILs) that have just been approved for melanoma, where we take tumors out, expand the number of T-cells that are able to be produced, and infuse those back into the patient. Those definitely work in melanoma. George Clinical actually helped in the development of TILs.

I would say to a cancer patient—it’s important to realize that the overwhelming majority of people with cancer don’t have a death sentence hanging over their head. It used to be that there was a very high likelihood, even for an early-diagnosed cancer, the patient was potentially dying. But now, particularly if you have an early-stage cancer, don’t give up hope. There’s a lot that can potentially be done. Even with metastatic cancer, the goal is that patients live with cancer, not die of cancer—to make cancer a chronic disease for these patients. Don’t give up. There’s a therapy that’s going to potentially work, and if it stops working, we’ll move on to another therapy that hopefully will work for a time. And just keep going—taking the next step after the next step, because we’re discovering more and more every day.

How would you sum up the most impactful way to balance the patient-science equation?

I want to point out again that the intersection between patient care and clinical trials is very, very important. And it’s one of the reasons that I continue to do work with George Clinical. I’ve done full drug development and molecular diagnosis and clinical trials—but George Clinical is where the rubber meets the road. I can provide information about what the patient with cancer would benefit from—how the process of being in a clinical trial could potentially be meaningful for that patient. I can make sure that the trial is well designed and that the trial answers the questions that it wants to answer.

From a certain perspective, it’s an ethical question. You don’t want to do a clinical trial that wastes patients’ time and their gift to the scientific world. You want to make sure that when you do a clinical trial, it’s with a drug that is most likely to work, have a good side effect profile and going to answer the question that will get that drug to other people. If you don’t ensure these things, you’re wasting the sacrifices and gifts that those patients are giving. It’s really important when you’re developing a protocol to ensure that every perspective is being taken into account. And George Clinical does an excellent job of that.

What do you do to refresh your mind, unwind, reset for the next challenge?

I’ve got four kids. Two are getting to college age, and that ends up being a lot of work and angst. My twins are in seventh grade, and their problems are the biggest that you could possibly have in the entire world. I don’t know that that necessarily resets my mind, but it certainly redirects it a little bit. One way I reset is a lot of traveling, both for work and for pleasure. It’s always great to be able to go see and interact with other people in this remote world we live in. And I really like to ski. Point me down a hill. I can usually get to the bottom still standing up.

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