Dr. Vivek Subbiah on Pioneering Precision Oncology and Global Clinical Trials | OncoInfluencers #13

Ravi Karra: Good day, everyone. And welcome to this episode of Onco Influencers.

I am Ravi Karra, VP of Oncology at Advanced Clinical, a clinical research services organization headquartered in Chicago. I’m also an editor with OncoDaily. We are very excited to have Dr. Vivek Subbiah as our guest today. Dr. Subbiah is currently the Chief of Early Phase Drug Development at Sarah Cannon Research Institute, Nashville, Tennessee. He obtained his MD from India. He completed two clinical fellowships, one in pediatric hematology and oncology and another in adult oncology at MD Anderson Cancer Center.

He worked several years at MD Anderson Cancer Center, rising to become the Executive Director of Oncology Research before moving to his current position. He is a prolific investigator, having conducted over 100 Phase I and II trials as the principal investigator and over 200 clinical trials as a co-investigator. He’s an expert in tumor agnostic precision oncology and has been at the forefront of practice-changing BRAF and tissue agnostic studies that led to approval by FDA, European Medicines Agency and other agencies across the world.

We are very thrilled to have you. Thank you for your time.

Vivek Subbiah:  Thank you so much, Dr. Ravi Kara for the generous introduction. It’s a pleasure and honor to meet you and thank you.

Ravi Karra: Please can you tell our viewers about your early years where you were born and raised?

Vivek Subbiah: Thank you so much for that question. So, I was born and raised in the southern Indian city of Chennai. It used to be called Madras before.

It was one of the major metropolitan cities in India and my dad was in banking. He moved to so many places, including Indonesia, but my parents made sure that my sister and I had continuous education. So, we stayed in the same place in Chennai and I went from kindergarten to 12th grade in the same school in Chennai.

I attended medical school in Chennai as well. Again, Ravi, you and I are from Chennai. Chennai, the world may not know, but it’s a beautiful beach town.

Home to the world’s second longest beach called Marina Beach and has a unique culture in a modern city. Early on, my mom had a master’s in education and a master’s in economics and she motivated me to be a public speaker, inspired me to read a lot right from my first, second grade, write a lot at the time. My parents really influenced my upbringing and helped me develop an independent thinking process and that process that served me through school and into my career.

There were no doctors in my family. My dad was a professor and agricultural scientist and then he moved into banking after getting an MBA. I was inspired mainly to think again about the world, to think about service, inspired by my grandfather.

My grandfather was an academic, a renowned scholar. He studied at Oxford, traveled widely, wrote more than 120 books. So he was instrumental in making me think about scholarly work, scholarly activities, service and need to contribute to society.

I used to spend a lot of time, especially the holidays with him walking on the Chennai Marina Beach. He would talk about fascinating things that had been a part of his scholarly work around the world, from world history, English literature. He again made me read Shakespeare, Milton and almost all Greek literature.

So again, you know that Marina Beach is studded with statues of world-famous personality scholars. So I read about all these scholars, read about all these personalities. It was inspiring to learn firsthand from many people who were there in that area and inspiring to talk to my grandfather.

He was a well-connected person. He knew several great personalities and he helped again, most importantly, he helped thousands of people with their careers, getting them education, getting them jobs, helping them with their lives. And I thought to myself like at around eighth or ninth grade, again, I can probably help people with their jobs or career like my grandfather, but it would be better again for me to save lives.

What else I can do better, right? Again, I can give livelihood and jobs, but saving lives I thought would be the next, you know, service to society. Again, that started my thought process.

And then I, again, in India, you can go from high school to medical school directly. So that started the thinking process for me to go to medical school. So once I finished my medical school in India, I moved to the United States.

I completed a combined residency in both internal medicine and pediatrics, but both certified in both in Cleveland, Ohio. And again, I met several mentors at Case Western and Cleveland Clinic and National Cancer Institute where I did some rotation there in NIH who inspired me to focus on oncology. Oncology is a fascinating science driven specialty that combines the research opportunities with clinical care of our most vulnerable patients and combined all of the specialties that I was really interested in because I was really interested in endocrinology, infectious diseases, and oncology had everything, right?

Research, clinical care, endocrinology, infectious diseases, thought process, thinking, you know, service to patients. It’s an evolving nascent discipline. And with my interest, you know, turned to clinical trials, I thought I could truly, truly, truly make a difference here.

And needless to say, today, I think it was the best decision I made to move into oncology and oncology research. So since then on, you know, post residency, I moved, I was able to get a fellowship at MD Anderson. I did a combined, again, a unique you know, a fellowship with in combined a pediatric hemonc and medical oncology.

Again, there was no set combined fellowship, but a unique place like MD Anderson can make it happen, right? So again, I did a, you know, fellowship in pediatric hemonc and a medical oncology. And I met several people there who inspired me to where I am right now.

Three people, I think I would, I should say, at MD Anderson during my formative years, Dr. Emil Freireich, who everyone knows is the godfather of oncology clinical trials. And Dr. Razel Kurzak, who is a world-renowned leader in drug development. And Dr. Pete Anderson, you know, who was a compassionate physician who specialized in medicine and pediatrics, a sarcoma physician. So it was so nice to have these early influences in my career. And again, to think about something unique, something novel. So again, that led to where I was in terms of my faculty at MD Anderson.

And then it continued on. It was a special privilege to be there. And I led, you know, I started there at MD Anderson as faculty.

So again, I think that that should be enough for my early life until I became faculty. Please ask further questions from now on.

Ravi Karra: Excellent. Excellent. Thanks.

That seems like a very brilliant journey. Now, what drove you towards clinical trials initially?

Vivek Subbiah: Again, I would say my mentors, right? Again, Dr. Freireich and his mentee, Dr. Kurzak had a major influence on my career. She formed this unique department at MD Anderson called the Drug Development Department or the Department of Investigational Cancer Therapeutics, treating patients independent of histology in clinical trials.

And, you know, talking to, you know, Freireich, Dr. Kurzak, Dr. Pete Anderson, and several others, I’m like, I should focus on a career in drug development and clinical trials. Again, new drugs, novel drugs, so that we can contribute for the, you know, next generation of research. Dr. Freireich, I got to really know him well because I was the chief administrative fellow running the graduate educational lecture series when he was a chair.

He’d invite famous speakers on who’s who in oncology. I used to interact with them behind the scenes, Nobel Laureates, you know, before their talks to introduce them. Freireich was sort of a grandfather figure to me, who inspired me and focused my thought process toward drug development and career in clinical trials.

And later, after like seven or eight years, I became the chair of the same graduate medical education committee that Dr. Freireich was chairing, and it was a special privilege. And again, you know, we used to discuss and bounce off a lot of ideas together. And since then, once I became faculty, it was an exciting time when genomic sequencing entered clinic, and there was an explosion of genomically targeted therapies and immunotherapy options that was coming to the pipeline.

And I was drawn to the concept of doing something different to benefit our patients rather than offering the same standard of care chemotherapeutic agents developed even before I was born. So again, since then, I’ve designed and led several first-in-human clinical trials, many precision oncology studies, starting with one of the first ever basket studies to be published in the New England Journal of Medicine. That led to the FDA approval of BRAF inhibitors in Erdheim-Chester Disease and a rare disease called Langerhans Cell Histiocytosis.

Since then, we designed a basket study called the ROAR basket study, rare oncology agnostic research. That led to the approval of dabrafenib and tremetinib for anaplastic thyroid cancer. Again, that was one of the most lethal cancers known to us.

And, you know, with a data set of 26 patients, we were able to get a drug approval. Again, subsequently, the same trial and same combination led to the first ever tissue agnostic approval in BRAF V600 positive tumors. Since then, I also led the RET inhibitor clinical trial right from the first human patient enrolled in the universe, I would say, led the FDA approval for both the selective RET inhibitor studies, selpercatinib and pralsetinib for lung cancer, thyroid cancer, medullary thyroid cancer, and a tissue agnostic approval for Selpercatinib as well.

Again, as you mentioned, you know, Prince PI designed several studies, PI over 100 studies, several practice-changing studies like lorbenectadine for small cell lung cancer, pemigatinib for FGFR-altered cancers. One of the, you know, main things Dr. Freireich used to say that we can conduct all kinds of studies. Many people do clinical trials for the sake of clinical trials, but we need to answer the right questions so that what we do in terms of clinical trial research benefits patients and is impactful in the real world.

How can we move the needle in the real world? The late Dr. Norman Jaffe used to say that randomized studies might get you a high-impact paper and may push you in career. That’s about it.

It’s just for your personal agenda, randomized controlled trials, but they are not really going to help that patient, especially, you know, doing placebo-controlled studies, especially in those arms receiving placebo. These quotes, you know, still really stuck in my head and inspired me to design studies, precision oncology studies that can really help patients and pushing the needle forward.

And now my, again, after leading all these FDA-approved, you know, therapies that can impact patients in the U.S., you know, again, I started working with all these companies to get these drugs approved, not just in the U.S., but across the world. But once the beginning is in the U.S. and then we need to get it approved across Europe. And, you know, my thought is towards global harmonization. We need to make sure that we need to think locally and act globally.

So, again, I do a lot of work, you know, helping seeing how we can improve access by getting approvals of these drugs globally.

Ravi Karra: Excellent. Excellent. Thanks a lot for that.

I quote you, research should be standard of care and standard of care should be researched. Please elaborate this for our viewers. Again, thank you so much.

Vivek Subbiah: So the thing is that right now, on an average, less than 5%, again, the literature may go back and forth, less than 5% of patients with cancer are enrolled in cancer treatment clinical trials. The quintessential paradigm of, you know, practice change for a disease is learned from the world of pediatric oncology, right? You know, that pediatric pre-BCL-ALL was once a deadly disease.

And it all started with treating patients on combination studies from Dr. Freireich’s time. Dr. Freireich designed the first ever study with combination agents, right? Eventually over time, you know, in the 70s, 80s, every pediatric patient was enrolled on a clinical trial nationwide.

So almost 80 to 90% of patients were enrolled in clinical trials that moved the needle. The whole village, the whole pediatric oncology community got together to move the needle for cancer. Right now in 2024, almost 96 to 97% of the patients with leukemia, pediatric leukemia cure.

How did this happen? It didn’t happen by fluke. It was a conscious decision by every doctor, every parent in that generation to volunteer for clinical research.

The whole community got together to move the needle forward. So there was incremental studies being done. And today we have that result.

So with less than 5% of patients being enrolled in cancer clinical trials, how are we going to meet the, you know, cancer needle in medical oncology? I think we can all do better. I think the whole, we need to have an all-hands-on-deck, all-stakeholder approach for moving the needle for cancer treatment clinical trials.

The only way is standard of care should be research and research should be standard of care. Again, we think about standard of care and research as two different silos. Again, before the COVID pandemic, the lay person, the lay people did not understand what clinical trials are.

Every day, you know, they were showcasing in all the, you know, news outlets about clinical trial, the clinical trial data being presented from the COVID clinical trial. So the lay public know what clinical trials are. So they understand the value of clinical trials.

So I think right now is a time that even if we can increase the enrollment of patients with cancer from say 5% to 10% or 15%, you know, we will be closer to our goal of curing cancer. Again, someone said cancer is not one disease, right? It’s hundreds and thousands of diseases.

Even if you think about lung cancer, it’s thousands of diseases. Colorectal cancer is thousands of diseases. Someone calculated that it’s going to take 1,200 years to cure cancer by this pace, you know, the same pace, if you are going to do research and trials.

So I envision a future where, you know, we can assault, you know, cancer in the early disease course. And that can happen only if everyone comes together, right? When standard of care becomes research and research should be viewed as standard of care.

Not just the oncologists, right? You need the whole healthcare team, patients, the caregivers, patient advocates, academic institutions, community centers, community hospitals, industry, industry makes the drugs, you know, CROs, contract research organizations, like everyone needs to come together, right? All stakeholders, the government, the FDA, all the regulatory bodies, the HTA bodies in Europe and others here.

Everyone needs to get together with an all hands on deck approach to move the cancer needle. People may think this is impossible. But let me tell you, during the COVID pandemic, with all hands on deck approach, and a program like Operation Warp Speed, this was possible.

When a virus in an unprecedented global pandemic, in a post-risk to the lives of humans, everyone got together. Within nine months of a pandemic, global pandemic, a vaccine, a drug was discovered, the virus genome was, you know, unraveled, a vaccine was discovered, phase one, two, three trials were done in nine months. And we were able to get the vaccine in nine months with an all hands on deck approach.

I think this is unprecedented. So I think, you know, personally, I think that cancer should be viewed as a public health emergency, just like COVID-19. You know, we all remember that time in the initial time of the pandemic, that every news media outlet used to show in the screen, the number of COVID cases, the number of deaths, and public got to know that it was a deadly disease.

I think we should start putting that for cancer. Patients are dying, millions of patients are dying every year with cancer. Cancer is a all hands on deck approach, just like COVID.

It’s going to take the same 1,200 years to cure cancer.

Ravi Karra: Thanks for that. Fully, fully agree with you that research should be the standard of care. And again, going back to the 5% of the population of patient population that’s participating to the clinical trials, just doubling that from five to 10, I think it’s going to make a huge impact.

Yes. Now, historically, what have been the biggest challenges that you have encountered when enrolling patients into first human clinical trials?

Vivek Subbiah: And again, the challenge is, you know, the first step is referrals, right? Referring patients to, you know, clinical trials. So that itself should start right from the first-line therapy, right?

Again, clinical trials are viewed as last-line option in most patients. It should be viewed differently. Right now, we have genomically targeted therapies, immunotherapeutics, antibody drug conjugates, and beyond.

I think all these drugs will work earlier and earlier in the disease course, right? In oncology training, we need to, you know, enshrine upon the young oncologists and the future oncologists that they should start thinking about clinical trials right from the first line of therapy, right? NCCN guidelines say that the best treatment or best care of patients is always in a consider clinical trials.

But, you know, to be honest, real world, there are no pathways for clinical trial reference, right? So again, it should be enshrined in the workforce. You know, first our workforce should be oncogenomic savvy, right?

80% of the workforce is not oncogenomic savvy. So we need to make sure that the workforce is oncogenomic savvy. Workforce is clinical trial savvy.

I think we need to have basic education of clinical trials for all oncologists and all healthcare team members so that they can think about clinical trials right from the get-go, right? Number one. Number two is access to clinical trials, right?

Clinical trials, at least in the U.S., are relegated to niche boutique centers, academic centers. So again, most of the patients, vulnerable patients with cancer, have to travel long distances to seek clinical trials. So one of the reasons why, personally, I moved to an institution like Sarah Cannon, as you know, is one of the world’s leading oncology research organizations conducting clinical trials.

And, you know, SCRI recently, a year ago, a year and a half ago, they had a giant venture with U.S. oncology research. And, you know, they are developing programs across an organization, a research network of more than 1,300 physicians in more than 250 locations in 24 states. So that, again, this, you know, gives us an opportunity to see how we can move and provide access to clinical trials to where patients are, not vice versa.

You know, we all think about, day to day, think about ordering something in Amazon Prime, right? I’m thinking about something like Amazon Prime, right? Amazon Prime is everything comes to you.

Right now, the patients have to go to clinical trials. I envision a future where clinical trials come to patients, right? I think that’s a bottleneck, right?

We don’t, patients, number one, is our workforce is not adept in clinical trials. They are not oncologically savvy. Number two is there is no access to clinical trials, first access to clinical trials.

Even if there are clinical trials, they are only in need centers. So there are many clinical trial deserts across, even in the U.S. If that is the state of affairs in the U.S., one of the most developed countries for clinical trial research, think about the rest of the world. Think about Latin America.

Think about Africa. Think about India. Think about many other countries, right?

That do not have access to these novel therapies. Many times, access to novel therapies is only through clinical trials, cutting edge clinical trials. So that’s that access to clinical trials.

And then granularly, the eligibility criteria. Eligibility criteria are so designed in such a way that, you know, only the fittest patients can get on clinical trials. We need to be pragmatic.

We need to be really pragmatic when we, especially a patient with cancer, is enrolled on a clinical trial to see how it can mirror the real world. And, you know, there are several initiatives by the FDA, EMA, and ASCO, ESMO, to see how the clinical trial ecosystem can design studies in a pragmatic way so that, you know, clinical trials do represent a real world and real life patients. I think those are the three major bottlenecks in the, you know, challenges in clinical trials enterprise.

Ravi Karra: Excellent. Thanks a lot. I think these are the three that we have also encountered as my role in running clinical trials across the globe.

I think not just in any particular country, but most often, these are the three recurring problems across the board, across the globe. Now, what drives you to do what you do every day?

Vivek Subbiah: I think that’s a great question. I think to, again, we are all, you know, temporary individuals in the world. If you think about that, if you think about the vast span of time, we are a dot, less than a dot in the universe, temporary people.

Again, in this temporary time, we can need to think beyond what we can do for ourselves and our family. Think about how we can contribute to something and see how we can contribute even in a small way. Right?

If I’m not asking everyone to be Mahatma Gandhi, Mother Teresa, or Martin Luther King, right? But everyone, each and every individual can contribute in their own way. And the pathway that has led me here is I’ve been trained in clinical trials and clinical trial research in one of the major academic centers, number one cancer center in the U.S., if not the world, if not the universe. How can I, myself, with my knowledge of the clinical trial, contribute to the society, right, in the community? Again, how can I marry that? How can I marry all that knowledge?

How can I take the knowledge to impact patients at a larger scale in an unprecedented way? So I think to myself, if not me, who? If not now, when?

So that’s what drives me to do what I do. Again, beyond the U.S., again, thinking about talking to so many of our colleagues across the world, seeing how we can harmonize clinical trials and drug access of these new medicines across the globe. I think that’s another thing I work on is that.

And I think this is the best time to be in oncology, right? Again, we have unprecedented advances in oncology. 20 years ago, they said we cannot sequence a human genome.

We took $3 billion to sequence a first genome. Right now, we can get it done for $1,000 in the U.S. Colleagues in India, China, Singapore, they say that they can get it down to $1 in the next decade, right? So any human being can be sequenced.

That’s number one. And then we have drugs to go after that. We have immunotherapeutics to go after that.

We have so many, so many different drugs. And I think we can use all this knowledge to move the field and advance the field forward. So again, this is the best of times to be working as an oncology drug developer.

And again, contribute even in a point, one way in advancing care for patients with cancer. I think that I can sleep better if I know that I contributed that.

Ravi Karra: Excellent. That was really brilliant. It was not only philosophical, but it also based on what really happened with the facts, for example, the Human Genome Project and so on.

So that was wonderful. Thanks a lot for your time. And it was very nice to meet and talk with you and get to know you.

Thanks a lot. Thank you so much, Dr. Ravi Karra.

Vivek Subbiah: Again, it was a pleasure and honor.

Previous episodes of OncoInfluencers

Episode 1: OncoInfluencers: Dialogue with Françoise Meunier

Episode 2: OncoInfluencers: Dialogue with Dean Crowe

Episode 3: OncoInfluencers: Dialogue with Nagashree Seetharamu

Episode 4: OncoInfluencers: Dialogue with Julie Gralow

Episode 5: OncoInfluencers: Dialogue with Lillian L. Siu

Episode 6: OncoInfluencers: Dialogue with Douglas Flora

Episode 7: OncoInfluencers: Dialogue with Pasi Jänne

Episode 8: OncoInfluencers: Dialogue with Tony Mok

Episode 9: OncoInfluencers: Dialogue with Fadlo R. Khuri

Episode 10: OncoInfluencers: Dialogue with Julie Ross

Episode 12: OncoInfluencers: Dialogue with Andrea Pola Eidelman