Advancing Cancer Care: The Novel Cancer Therapeutics Center

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic directing the Taussig Early Cancer Therapeutics Program and co-directing The Cleveland Clinic Sarcoma Program. Today I'm very happy to be joined by Dr. Wen Ma, Director of the Novel Cancer Therapeutics Center. He's here today to talk to us about the Novel Cancer Therapeutics Center here at Cleveland Clinic. Welcome Wen.

Wen Wee Ma, MBBS: Thank you, Dale. Thank you so much for the opportunity to come to your program.

Dale Shepard, MD, PhD: Absolutely. Give us a little bit of a background, what you do here at Cleveland Clinic, just to start things off.

Wen Wee Ma, MBBS: Yes, so I'm a medical oncologist. My focus is on GI cancer types, and I'm also involved in the early phase drug development program, as well.

Dale Shepard, MD, PhD: Excellent. We're going to specifically talk about the Novel Cancer Therapeutic Center. Give us a little bit of an idea of what does that means? What are we trying to accomplish with the center here?

Wen Wee Ma, MBBS: Yeah, that's a fantastic question. Curing cancer and treating cancer is a very important endeavor that we do at the Cancer Institute. We're always looking at what's the latest treatment that's available, and in this country that would involve a lot of clinical trials. Given the audience, we know that the treatment that becomes promising will go into phase one clinical trial development. That historically has been the situation where we have drug treatment, you go into phase one trial and then move on. But the landscape really became very complex over the last 10 to 15 years. No longer is a pharmaceutical agent focused endeavor. It's becoming a multidisciplinary enterprise. Just for example, we have immune checkpoint inhibitor, but then after that we have antibody drug conjugate, and then, given that there is proof in principle that immune system can be leveraged as an anti-cancer modality, then we start seeing CAR T-cells, or modified cell therapy.

Then we start seeing theranostic, where radioisotopes, radioactive sources tack onto a target-seeking construct that is injected into patients. From all those modalities, we're starting to look at treatment that would really need a multidisciplinary approach, nuclear medicine, radiology, and also traditionally a non-oncology-based specialty, such as endocrinology, rheumatology, to really help us help manage the survivors from immune checkpoint inhibitor treatment. Given that changing landscape, there's really a need to have a concerted effort to bring those treatments to our patients. That's where really the role of Novel Cancer Therapy Center really focus on, is really to help the cancer enterprise, Cancer Institute to really coordinate and help grow that capability so that we can really bring the latest complex treatment to our patients.

Dale Shepard, MD, PhD: Just to backstep a little bit. Clinical trials, really, really important. We don't get new drugs available unless we do these clinical trials. Historically, what are some of the barriers to enrollment? Why don't more people enroll in these trials?

Wen Wee Ma, MBBS: That's a good question. I think the first thing that we really need to think about is the barrier for patients to get in. A lot of times, we need the information. Even if we're doing great work, if the information doesn't get out such as what daily are doing, really getting the information out, that's a very important part of it, getting that information out. That information is going out to not just patients, but also to our colleagues in oncology. Having to help inform and educate our colleagues about what's available in early phase trials, that'll be fantastic. I appreciate the opportunity to come to your program today.

The other piece in early phase trials is really it's a very dynamic landscape. For those of us who have worked in phase one trials or been involved in that, we understand there's this concept of slot availability, which means that the study is available, but we have to wait for the slots. In this day and age, slots can be competitive from other institutions in the country or from institutions outside of the country. We're competing for the slots for our patients for that particular treatment. There's a lot of moving parts for early phase trials and dosing comes together to present quite a barrier to bringing those early phase trials to our institute.

Dale Shepard, MD, PhD: Then the other thing, and you mentioned the new things like ADCs and different types of treatments, but the trials themselves have changed so much. A few years ago, we were mostly thinking about chemotherapies and things and something you expect to work on a wide wide range of tumors. We had these wide inclusion criteria and now they're very, very focused. What are your thoughts in terms of the pros and cons of how specific these trials have become?

Wen Wee Ma, MBBS: That's an interesting question because you have a similar experience. When we first start out where we feel like it's a sledgehammer, when we're doing chemotherapy, we kind of sledgehammer and then we have a randomized trial which is non-selected. We ask ourselves, "Are we doing more harm than doing good?" Around the same time, we started using this molecular technology so that we can actually further define the biological processes in those cancer types. Then we suddenly realized that we can actually do a lot for a small, specific group of patients. That's where, really, the complexity comes in, where we're going after cancer based on their biology, recognizing that we can help a small group of patients very well, but we need to know who they are and what kind of characteristics to look for.

Then that resulted in clinical trials that are very specific for a specific population. In that regard, you become a barrier and challenge in terms of finding the right patients and needing more sites. There's recognized across the board, as you know, they are in early phase development and you are the director of our early phase cancer program, that you know that it's very competitive to try to get those trials. At the same time, we need to find those grown patients and even if it's just benefiting one patient, we should really think about opening those trials. That can be very challenging for our programs.

Dale Shepard, MD, PhD: We have this Novel Therapeutic Center. How logistically are we setting this up to get those right patients in, get the right trials in? What does this look like?

Wen Wee Ma, MBBS: Yeah, that's a good question. A lot of times I would imagine myself as a cancer patient seeking care. A lot of times we look at, "How can I get all the information in the most efficient way?" The other way to look at it is one-stop shopping. One-stop shopping with a seamless experience. If I'm a cancer patient seeking care to understand what kind of early phase trials are available, I want to be able to step into the Cancer institute and have all the information in front of me.

From that regard, and Dale, you have been instrumental in setting up our Novel Therapeutics Clinic, is really to provide that experience where patients who needs this kind of services and this kind of treatment options be able to step into the Novel Therapeutics Clinic and have a one-stop experience where the providers come to them, where the study coordinator comes to them with all the information so that we can help the patient understand the process, understand the options, and then help also to link them back with their primary oncologist so that everyone can have an informed discussion about what's the right strategy and what's the right clinical trial for that patient.

Dale Shepard, MD, PhD: How are we working within this center to incorporate things that, primarily we focus on solid tumors at this point, how are we incorporating things like novel cellular therapies and those things that are maybe traditionally been more hematologic and not as much early phase solid tumor?

Wen Wee Ma, MBBS: Yeah, that's a fantastic question. Again, Dale, you and I, we went through a period of time where we think that there should not be any more cancer treatment given to inpatients. There's a period of time where we think that as a solid tumor doc, I will be in the clinic. But you know what? With the ADC bispecific, and with the immune checkpoint inhibitor treatment, with the T-cell engagers, with the cell therapy, we are having to deal with cytokine release syndrome, which can be best managed and safely in a hospital setting. That's where the cell therapy in this modality brings the challenge of working seamlessly between the outpatient clinic and also the hospital service, when traditionally solid tumor docs, we don't deal with that very well. That is the focus for the center, where we're looking at what can we do in a collaborative manner to really build a seamless experience for the patients who need this kind of treatment where they come to the Novel Therapies Clinic and they understand the process, seamlessly get the treatment in the hospital, and then coming back to the outpatient setting to continue their management.

It sounds straightforward, but Dale, you've being involved in it, it's not that straightforward. I think there's an area of opportunity for our clinic enterprise to really go into and also an opportunity if we do it well, patients at Cleveland Clinic would definitely benefit from that.

Dale Shepard, MD, PhD: Because we've been able to work toward collaborating with our more traditional hematologic colleagues too, as you say, a patient comes in and they may see us as solid tumor docs. The therapies might be related to cellular therapies.

Wen Wee Ma, MBBS: Exactly, Dale. Traditionally, this kind of therapy is managed very well by our colleagues in hematology, malignancy, BMT, leukemia. It's really bringing us back together to really look at how we take care of solid tumor patients.

Dale Shepard, MD, PhD: Within the center, we're looking at these very early cancer therapeutics and we're looking at these more cellular therapies. One area that as we have these newer therapies is the reactions, people's adverse effects. You mentioned getting involved in things like endocrinology and things like that. How is that being incorporated into this center?

Wen Wee Ma, MBBS: Yeah. You bring up a very important question that we are starting to need to deal with. It used to be a pediatric problem, where pediatric cancer gets cured, but they have to deal with long-term side effects. But in adult solid tumor, it's starting to happen. With the immune checkpoint inhibitor therapy, melanoma, lung cancer patients who are suffering from side effects from immune treatment such as autoimmune diseases, their survival is starting to lengthen to the extent that it is important to help patients manage those side effects. To a certain extent it's a survivorship. A lot of these processes, diseases and conditions related to immunotherapy are starting to fall outside of our expertise, what we are trained for. How do we manage autoimmune diseases, how do we taper immune suppressants with the newer agents? Those are questions that, as oncologists, we are new to.

But you know what? Our colleagues in other subspecialties such as rheumatology, endocrinology, gastroenterology, dermatology, they actually have a lot of experience in that. I think there's a good opportunity where we come together with a multidisciplinary approach to really take care of the patient in a good continuous spectrum rather than patient come to see oncologist and they stick with oncologists because gone are the days where actually the patients are having longer benefit that we need to involve more of our colleagues in this management.

Dale Shepard, MD, PhD: Really having solid support in a lot of other disciplines strengthens the clinic.

Wen Wee Ma, MBBS: Exactly, exactly.

Dale Shepard, MD, PhD: Another type of therapy you touched on was biomarker driven therapies, what might be considered genomic therapies. We do gene testing and there's trials that might be linked to that. There are bioinformatics issues and how are we incorporating those trials and the data we get from that testing into trials?

Wen Wee Ma, MBBS: Right, right. You get back to the point where we discussed before, whereas we know more we can help more patients, but the patient population starts shrinking. It is challenging to then mesh those clinical trials with those [inaudible] patients. I think at our institute, we are actually doing a fantastic job with all the resources available. We are having innovative engagement with clinical trial sponsors in really bringing the concept just in time activation on clinical trials. What it is that if we do find a rare mutation, and then with our partners in the pharmaceutical companies, if we do identify appropriate trial, we can actually activate it within one to two months. Dale, you have experience, and I think we have a record of about 40 something days to activate a trial for a patient who needs that trial. I think we're making a lot of strides in that regard by thoughtful and deliberate and strategic partnership.

Dale Shepard, MD, PhD: One thing when you talk about barriers to clinical trials, people's access to get to a center that has trials, the rigors of some of these early trials in terms of testing and things like that, what kind of work is being done or anticipated to be done in terms of how we logistically do trials and make it easier for patients to participate?

Wen Wee Ma, MBBS: Yeah, I think in order to execute a clinical trial, it's a very complex endeavor. We need a lot of research staff, and a lot of doctors like you and me to really be involved. Really, we are in the process of really looking at an experience where the patients will come in and they wouldn't even notice there's a research staff there. It's a process where we need to think about how we streamline study conduct so that we are there to help in the background and the focus is really between the discussion of the clinic doctor, and provider, and the patient. Then in a process where we have our research staff really helping in the background to get those processes done, get those studies to the patients.

Dale Shepard, MD, PhD: I guess we learned during COVID to be flexible. Maybe the ability to push companies to allow us to do labs in the patient's hometown or things like that could be helpful.

Wen Wee Ma, MBBS: Yes, exactly. Dale, you brought up another point. That current challenge is very difficult for many different reasons for patients to come to our campus to receive care. The other focus in the center is really how do we bring the clinical trials and care to the patient. Like what you described from the pandemic experience, we learn how to do virtual care. Definitely it's a process, whereas we develop out the infrastructure, we are looking at how to bring those clinical trials to the patient closer to their home.

Dale Shepard, MD, PhD: Within our own Cancer Institute here on main campus, our regional practices, our local community providers, education is huge. A lot of patients are being, really, most of our patients here in the Cleveland Clinic are seen in the region, not here on main campus. How are we getting those providers, those patients engaged, know what we're doing here, offer them those same trial benefits?

Wen Wee Ma, MBBS: Yeah, so that's a good question. You bring into focus of what our institute have been doing, strategically building up the clinical trial infrastructure in our regions in the east, west, and also south as well, in providing the resource of the clinical trial coordinators, also, the research pharmacy support, and also to help engage and educate our colleagues in the regions as well. Definitely in oncology, all of us are very interested and supportive of clinical trials because we understand that is really the best way to get the latest treatment for our patients. I think with that kind of background and interest, I'm very sure that we'll be able to engage our colleagues, wherever they are, really to bring the early phase trials to the patients.

Dale Shepard, MD, PhD: As the director overseeing this clinic, this center, you've made great changes so far. What are you most proud of so far?

Wen Wee Ma, MBBS: What I'm most proud of so far, I think we have a good team. I think that's important. It cannot be stressed more that it is very important for our team to function very well. I'm very proud to say that we have established a process and a team dynamic that I think will bring us to the next step to really making a success here.

Dale Shepard, MD, PhD: That's fantastic. Of course, we need new therapies, better tolerated, better efficacy. This is the way that this happens. I appreciate your support in making this happen and your insights.

Wen Wee Ma, MBBS: Yeah. Thank you, Dale. Thank you for your time today, and I'm glad to be here.

Dale Shepard, MD, PhD: To make a direct online referral to our Taussig Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You'll receive confirmation once the appointment is scheduled.

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