Merging Clinical Trials With the Clinic: Bladder Cancer Therapeutic Advances With Dr. Brad McGregor

Dr. Brad McGregor is the Director of Clinical Research at the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute and the latest Section Editor for the Muscle Invasive Bladder Cancer (MIBC) knowledge hub for GU Oncology Now. With a distinguished career that began with an unconventional path through military medicine, Dr. McGregor has become a leading figure in GU oncology. His work has contributed to significant advancements in the field, including his involvement in the pivotal EV-201 trial, which led to the FDA approval of enfortumab vedotin (EV) for metastatic urothelial carcinoma (mUC). Dr. McGregor’s innovative research continues to shape the future of GU oncology, particularly through groundbreaking studies like the DAD trial, which explores the potential of combining different antibody-drug conjugates (ADCs) in the treatment of bladder cancer.

To get to know Dr. McGregor, GU Oncology Now sat down with him to discuss his journey, from his early influences and mentors to his current role at Dana-Farber. In this conversation, Dr. McGregor shares insights into his day-to-day responsibilities, the exciting developments in the MIBC space, and the challenges facing the field of GU oncology. He also offers valuable advice for aspiring oncologists, emphasizing the importance of setting clear goals, being open to opportunities, and maintaining patience and perseverance throughout one’s career.

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Let us start with your career journey leading up to your current role as the Director of Clinical Research for the Lank Center of Genitourinary Oncology at Dana-Farber Cancer Institute.

Brad McGregor: It is hard to believe I have been at Dana-Farber for 8 years now; I joined in 2016. My career path has been somewhat unconventional from an academic medicine standpoint. My father was in the Air Force, so we moved around a lot during my childhood. When it was time to consider medical school, I enrolled in the Health Professions Scholarship Program, which is essentially the ROTC program for doctors, where the Air Force helps with medical school tuition. I attended Tufts for both my undergraduate and medical school education. Through the scholarship, when it came time to choose a residency, I was assigned to the military, and I completed my residency in San Antonio. I then went on to fellowship and served 6 years as an active-duty physician, working in Texas and California. I even spent a brief period in Afghanistan.

As my time in the military was coming to an end, I was practicing as a general oncologist. I realized that while I could be a very good general oncologist, it is difficult to be an expert in every area of oncology; it is challenging to stay on top of all the data from every clinical trial and to feel truly confident administering all the different treatments. This led me to specialize, and GU oncology felt like a natural transition. It allowed me to narrow my focus from a wide range of diseases to just 3 or 4. Over time, I was hired initially as a clinician, but my role evolved into that of a clinical trialist, with much of my research now focused on bladder and kidney cancer.

Were there any early experiences during your medical school journey, or any particular mentors, who played a significant role in guiding you towards GU oncology?

Brad McGregor: There were certainly influences from my childhood that led me to oncology. When I was 10, my dad was diagnosed with acute lymphoblastic leukemia, and he was actually cured through aggressive chemotherapy regimens. It is a small world; the nurse leader at the hospital where I did my fellowship was the same nurse who treated my dad. As for choosing GU oncology specifically, it is difficult to pinpoint any key factor. I have had many mentors along the way who have significantly shaped my oncology career and helped me get to where I am today.

My move into GU oncology was somewhat serendipitous. I was looking to relocate to the east coast and interviewed for a position in GU oncology at Dana-Farber. It felt like a natural transition for me. During that time, there was a gap in our group when it came to bladder cancer specialization. I had the opportunity to lead the EV-201 trial at our site, and we became the lead accrual site internationally for that trial. By staying open to opportunities as they arose, I have been able to advance my career to where it is today.

Let us talk about your current role. On a day-to-day basis, how would you describe your responsibilities? Could you break it down in terms of how much time you spend on clinical care versus research versus administrative duties?

Brad McGregor: To be a clinical trialist, it is essential to maintain a clinical practice. You cannot be effective in clinical trials without seeing patients regularly. I am in the clinic at least 2 days per week, often with additional visits here and there. If I am away for a meeting, I will still make time to see patients. So, 2 days per week are dedicated to clinic work.

The rest of my time is divided among various roles. I have administrative responsibilities at the institute, where I oversee clinical trial operations for our group. This involves working closely with our research managers and the regulatory team to determine which trials we want to invest in and how to allocate resources to continue advancing care in GU oncology. At any given time, we have over 20 trials open, which requires significant coordination.

Beyond the administrative side, I am also deeply involved in research. This includes leading my own clinical trials, writing investigator-initiated trials, and collaborating with industry partners to ensure we have the right trials available at our site.

You mentioned the EV-201 trial as a significant milestone in your professional life. With 20 ongoing trials that you are coordinating, along with your own research, I would love to hear your thoughts on what you consider to be the 2 or 3 most impactful studies or contributions you have made to the field of bladder cancer.

Brad McGregor: Being a part of the EV-201 trial, which led to the FDA approval of EV for mUC, was incredibly exciting. We were using this game-changing drug years before it received FDA approval, so it was no surprise to see the promising results emerge. That experience was fascinating.

Another impactful study I have had the privilege to help lead is our Double Antibody Drug Conjugate (DAD) trial. This was the first trial ever to combine two different antibody-drug conjugates (ADCs), not just in bladder cancer, but in any malignancy. We demonstrated that combining EV with sacituzumab govitecan (SG) could be done safely with granulocyte colony-stimulating factor support, achieving a remarkable objective response rate of 70%. Although the sample size was small, the results were impressive, and I have several patients who have been off therapy for over 1 or 2 years without any disease progression.

This trial really offers a paradigm shift: can we effectively combine ADCs? It laid the foundation for our ongoing DAD-IO trial, where we are adding pembrolizumab to EV and SG. What is exciting is that this work has sparked interest beyond bladder cancer. I have received calls from investigators in lung cancer and other fields, asking about the rationale for combining different ADCs. The potential for rational combinations of ADCs with distinct targets, different payloads, and non-overlapping toxicities is enormous, and I am thrilled to think about the next steps in this area.

The MIBC space seems poised for significant advancements over the next few years, perhaps even within the next year. Could you discuss what key questions need to be answered, the therapies being developed to address them, and the timeline for achieving these solutions?

Brad McGregor: Urothelial carcinoma has experienced a revolution in advances after decades of negative trials. Last year, we saw a standing ovation for the data on EV plus pembrolizumab at ESMO, which is indicative of the excitement in this field. The breakthroughs we have seen in the metastatic setting are beginning to transition into the perioperative space.

Just in the past year, we have seen data showing that pembrolizumab, when used after surgery in high-risk disease, improves relapse-free survival. Similarly, the data for adjuvant nivolumab, after 1 year of follow-up, indicated not just a trend toward improved relapse-free survival but also overall survival, which is fantastic. This evidence is shaping our understanding and suggests that immune checkpoint inhibitors likely have a role in the adjuvant space.

There are also several ongoing trials aiming to transform the entire perioperative approach. For example, a recent press release from the NIAGARA trial indicated that adding durvalumab to cisplatin-based chemotherapy improved overall survival, and this was observed in the first analysis, which is significant. We have had years of follow-up for adjuvant nivolumab, and now we are seeing an OS benefit in the first analysis with durvalumab. We look forward to seeing more detailed data at future meetings.

In addition, trials involving cisplatin-gemcitabine combined with nivolumab and pembrolizumab are underway. Moreover, the EV plus pembrolizumab trials are particularly exciting because they offer an option for patients who cannot tolerate cisplatin. Currently, if a patient cannot receive cisplatin in the perioperative setting, we typically proceed with surgery and then reassess. However, if the EV plus pembrolizumab data translate well into the perioperative space, we could be curing more patients because we will be able to offer therapy to a broader patient population before surgery. This could be a major game-changer, not only by improving outcomes if the trial is successful, but also by providing a new treatment option for patients who otherwise would not be eligible for therapy.

I believe we are on the cusp of a very exciting time. My hope is that these advances will continue to progress, and while the developments in the metastatic setting are crucial, they may become less so as we aim to cure more patients in the upfront setting, potentially reducing the need for metastatic therapy altogether.

There is often a lot of discussion about the current state of GU oncology and where the field is heading. In your opinion, what are some of the most pressing issues or challenges currently facing the GU oncology field? Is it a lack of manpower, accessibility or availability of therapies, or something related to clinical trials? What do you see as the largest issue today?

Brad McGregor: We are very fortunate in the GU oncology field because it is a highly collaborative community. When we come to these meetings, it is not just about hearing the latest data; it is also about meeting in person, collaborating, and sparking new ideas. I think post-COVID, the return of in-person meetings has been incredibly valuable in reigniting those conversations and driving the field forward. This collaborative aspect of academic medicine and oncology is something I find extremely rewarding.

In terms of challenges, I do not think there are issues that are unique to GU oncology compared to oncology in general. A significant challenge is ensuring that clinical trials continue to progress and that we have the necessary infrastructure to support them. For a long time, the infrastructure—such as research coordinators and other support staff—was understaffed. Although this is improving, it is essential to recognize that successful clinical trial operations involve more than just the doctor and the patient. It requires a whole team, including researchers, research coordinators, regulatory teams, and data entry staff.

It is crucial that we build and maintain this infrastructure, not just at major academic centers but across the country, so that patients everywhere have access to clinical trials. COVID taught us that telemedicine has a role, and it is pushing us to think differently about how we conduct clinical trials. This could be key in improving accessibility and addressing the underrepresentation of underserved populations in clinical trials. Applying trial data to these populations can be challenging, so as a field, we need to continue our efforts to enroll a diverse spectrum of patients in clinical trials, not just in GU oncology, but across all areas of oncology.

In your position, one of the roles you take on—perhaps something that does not necessarily appear on your CV—is that of an educator and mentor to many people. What advice would you give to aspiring GU oncologists who are just entering the field today?

Brad McGregor: When I reflect on my own career, 1 of the key pieces of advice I received early on during my fellowship training was from Dr. Mike Oswald, who was my program director in the military. I remember presenting a case to him, and he stopped me mid-presentation to ask, “What are your goals? What are you hoping to achieve for this patient?” He emphasized the importance of always having a clear goal, whether it is curative or palliative, and what you are aiming to accomplish.

This advice has stayed with me, not just in patient care, but in shaping my career as well. I believe it is crucial for anyone entering this field to think about their own goals. What do you want to achieve in 5 years? Ten years? When I first interviewed at Dana-Farber, I was applying for a clinical position, and I told them that while I wanted to be a good GU oncologist, my 5-year goal was to become a clinical trialist. At the time, they advised me to focus on the clinic, but having that long-term goal in mind was important.

It is essential to set goals, even if they seem unrealistic or if others might not immediately see their potential. Work toward them, and be open to the path you might take to get there. My journey was not the traditional path for academic medicine, but I arrived nonetheless. Having a clear goal and an open mind is key.

Early in your career, do not make “no” your default response. You cannot say “yes” to everything, but it is important to be open to opportunities because you never know where they might lead. If you enter a position with a narrow focus, it can be difficult. It is often easier to find a niche than to create a niche. By being open to unmet needs and looking for ways to fill them, you will have a much more successful run. This approach helps avoid competition and allows you to carve out your own unique path.

Finally, be patient. Success does not happen overnight, but it does happen if you stay focused on your goals and remain open to the opportunities that come your way.