Our Industry Voices series showcases our clients’ innovative work and breakthrough therapeutics in oncologic indications and other critical areas of medical unmet need.
In this article, we are delighted to share an interview with Kurt Gunter, M.D., Chief Medical Officer of Cell Medica in which he discusses his work, his views on the key advancements in oncology development, the unmet needs yet to be overcome, and the importance of strategic biostatistics input to his organization. Read on, or click here to download a copy of the article to read offline.
Can you tell us about your role and your work at Cell Medica?
Cell Medica is focused on cellular immuno-oncology, using cellular therapy to treat various types of cancer. As the Chief Medical Officer, I’m responsible for regulatory affairs, clinical operations, and medical affairs. That entails designing development programs and clinical protocols to allow the company to achieve its objectives. Namely, to demonstrate the safety and efficacy of all of our products in various cancers.
What do you see as the key opportunities in oncology development today?
Clearly, there’s been a lot of progress in the treatment of cancers even looking back over just the last five years. If you look back over the last several decades, the progress has been tremendous. But in spite of that, there remain major unmet needs. For example, there’s been limited development of new therapies for patients with small cell lung cancer. And while there are some products under development in acute myelogenous leukemia (AML), patients still do poorly in general, and elderly patients often cannot receive full treatment due to toxicities. So, there are still significant opportunities for improving the delivery of care to oncology patients.
Where might there be opportunities to overcome those continuing challenges?
It’s increasingly difficult to find patients for clinical trials. There are a lot of drugs being developed in oncology, and there is a great deal of competition between sponsors to find appropriate patients for their studies. To give some context, at any given clinical center, there might be ten or twenty different pharmaceutical companies sponsoring different studies, and often investigators have the option
of enrolling patients into several different ones. In the end, enrollment decisions can boil down to which study has the most academic interest for the investigator, making it much more challenging to recruit patients for studies. This results in pressure on sponsors to get more done with less; to demonstrate your clinical objective with fewer patients. This challenge drives innovative clinical trial design.
"Cytel has been very valuable for me and for our company because we’re a small organization. We don’t have any in-house biostatisticians, but when we need one we really need one badly! "
Immunotherapies need distinct clinical trial designs. What are some of the key aspects to consider?
There’s no doubt that the gold standard for outcome measure in cancer studies still remains survival, and that will probably not change. However, the difficulty with survival studies, especially within longer-term oncologic illnesses is the duration and the need for a large sample size. They can be confounded
by crossover. So there is a need for other endpoints that lead to outcomes more quickly, and allow sponsors and physicians to make decisions about the trial earlier. For example, progression- free survival in many studies is considered to be a valid measure of the clinical impact of the therapy. However, the problem with that is how you measure tumor progression. In the past, with solid tumors and the use of a standardized RECIST measure, you simply did a CT scan and measured the size of the tumor. If the tumor shrunk, that represented an improvement, and if it got bigger, that was progression.
With immune therapies, which don’t act directly on the tumor, but instead bolster the immune response to it, patients’ courses can actually improve without the observation of a direct tumor shrinkage effect. This means new tumor imaging protocols for immune therapies are needed to account for this. It’s an area that I don’t think the field has effectively grappled with yet, although there are some provisional new measures available for lymphoma and for solid tumors.
What value do you find that statistical collaboration can bring to your development planning and decision making?
Cytel has been very valuable for me and for our company because we’re a small organization. We don’t have any in-house biostatisticians, but when we need one we really need one badly! Cytel has always been there for us when we needed biostatistics help. Often, we seek help not only with the nuts and bolts of number crunching and calculating sample sizes, but also more strategic input. We have already discussed some of the pressures in conducting clinical trials nowadays, and the need to extract more data from smaller sample sizes due to the competition for patients. Without infinite financial resources, we need to get the most value that we can from a clinical trial, and so having effective strategic biostatistics input early on, even at the protocol synopsis design phase is very important to us. Also, in my view, there’s a distinct move away from traditional approaches. Instead of individual Phase 1, 2, and 3 trials, there is a drive to combine studies, where based on an interim analysis at an early stage you make a decision whether or not to move forward in the same study. These are sometimes referred to as expansion cohorts, and in some oncology indications, a Phase 1/2 trial with large expansion cohorts can actually lead to product approval, especially in the US. We need solid decision-making criteria to help determine whether or not we should move to expansion cohorts or to identify which patient cohorts to expand. Having biostatistics input in setting up good prospective decision-making standards in a clinical trial is helpful, and Cytel has been very useful to us in helping us develop these.
"One problem with conventional approaches is that often patients receive extremely low doses that are unlikely to have potential benefit. "
How does biostatistics input help you specifically in early phase development?
We are working with some novel therapies that have never been tested in people before, so we want to be extremely careful and above all not cause toxicity. Therefore, we generally start at very low doses and gradually escalate. One problem with conventional approaches is that often patients receive extremely low doses that are unlikely to have potential benefit. A traditional dose escalation approach in oncology is a 3 + 3 design, where you treat at least three patients at every dose level, perhaps more if you see toxicity. If you have ten dose levels that you have to treat sequentially, then in a 30 patient study it could take you two years to get to an effective dose. There are ways to accelerate dose escalation using sophisticated biostatistical approaches that minimize the number of patients treated at low dose levels if no toxicity is seen. That’s another area in which Cytel has been, and will be very important to us.
There is a lot of attention at the moment on basket trials as a particularly promising strategy in oncology development. Can you tell us about what you see as the opportunities and barriers in the use of basket trials?
There are different kinds of basket trials, and we are interested in one particular type. At Cell Medica, we’re developing several different targeted therapies, and one paradigm for drug development that we’re interested in pursuing is a tissue agnostic approval. If there is a marker X, that is expressed in a number of different malignancies, and you have a therapeutic that’s active against marker X, then rather than conduct separate studies in each of the malignancies, it’s possible to conduct one big study enrolling only patients that are positive for marker X, and then analyzing those patients as a group. That’s the kind of basket trial in which we are interested. A problem with that type of design is that it leads to potentially very large studies. So we need a way to analyze the study at interim points and decide whether to continue with the entire study, or move forward only with subsets of patients. Again, that’s where a biostatistics-based rationale and decision-making can be very useful.
What impact do you hope your work will have?
That’s a simple question to answer, but on a practical level may be more difficult to realize. Our goal at Cell Medica is to transform patients’ lives through cellular immunotherapy. If we can save one patient’s life, I’ll be thrilled. If we can save more than that, I’ll be even more thrilled. Ideally, we’d like to play a role in the continuing advancement of immunotherapy. I believe that in the next decade, the textbook of cancer treatment will relegate chemotherapy and older therapies to historical context, and such methods will be discussed primarily in terms of their severe side effects and limited efficacy. The main body of the cancer treatment textbook will be devoted to therapies that manipulate the immune system to tip the balance in favor of patients, with much lower toxicities. We want to be a part of that textbook.
Many thanks to Kurt Gunter, M.D for sharing his experiences and work with us.
Interested in learning more about innovative oncology trial designs in practice? Click the image below to download our recent eBook.
About Kurt Gunter
Dr. Kurt C. Gunter, M.D., Ph.D., FASCP, has been Chief Medical Officer of Cell Medica since March 2013. He served as Vice President for Clinical Development at Hospira Chicago, USA until March 2013. He has previously held leadership positions at ViaCell, Transkaryotic Therapies and the US FDA, all in the fields of cellular and gene therapies. Dr. Gunter is a member and past President of the International Society of Cellular Therapy. He is also a member of the American Society of Clinical Pathology, American Society for Hematology, American Society for Clinical Oncology, International Society for Stem Cell Research, American Society for Blood and Marrow Transplantation and the American Association of Blood Banks. He is board-certified in Clinical and Anatomical Pathology and Transfusion Medicine. Dr. Gunter has an M.D. from the University of Kansas School of Medicine and a B.S. from Stanford University.
About Cell Medica
Cell Medica is committed to transforming patients’ lives through developing the significant therapeutic potential of cellular immunotherapy for the treatment of cancer. In collaboration with its strategic partners, Cell Medica is developing a range of products using three proprietary technology platforms including activated T cells, chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs). Cell Medica’s lead product is CMD-003 being tested in an international Phase II trial for the treatment of cancers associated with the oncogenic Epstein Barr virus. Cell Medica is working with the Baylor College of Medicine and the University of North Carolina to develop next- generation CAR-modified NKT cells including an off-the-shelf product. In the field of engineered TCRs, the company is collaborating with University College London to develop the Dominant TCR technology platform.
Cell Medica is headquartered in London with subsidiaries in Zurich and Houston.