First person profile: Robert L. Ferris, MD, PhD

Abstract

Early in his oncology career, Robert L. Ferris, MD, PhD, was talking with one of his mentors about his research on cellular therapies and challenges to making immunotherapy work, specifically in head and neck cancers—his specialty. The mentor was Olivera (Olja) J. Finn, PhD, founding chair of the Department of Immunology at the University of Pittsburgh, where Dr Ferris had started his oncology career 5 years earlier. It was 2006, and cetuximab had just been approved. “We knew cetuximab benefitted about 15–20% of patients, but we couldn’t figure out who they were or why they benefitted,” he says.

That conversation sent him on a new track to find out. He became one of the first adopters of developing neoadjuvant trials to understand the immune mechanisms of action of immunotherapy agents in what he calls “reversing direction” from his prior research attempts. His former research focused on making immunotherapy and dendritic cells work by taking an active agent in the clinic and elucidating its mechanism of action. His initial “splash,” as he refers to it, was to show that cetuximab has immune mechanisms of action in a set of patients via natural killer cells, dendritic cells, and lymphocytes.¹

Years later, he continues to be part of the now vibrant community of physician–scientists who are using the neoadjuvant operative platform to more quickly and efficiently understand the mechanisms behind why some immunotherapy agents work in some patients and not in others. The approach harnesses his surgical practice and drives his laboratory work.

His laboratory is extending this work into looking at why some patients with recurrent metastatic head and neck cancer benefit from the anti–programmed death 1 (PD-1) monoclonal antibody nivolumab, as demonstrated in the pivotal phase 3 CHECKMATE 141 trial,² of which Dr Ferris was the lead author. The trial was the first positive phase 3 trial showing a benefit of immunotherapy for head and neck cancer and led to the US Food and Drug Administration’s approval of nivolumab for head and neck cancers.³

More recently, his laboratory has been trying to figure out how combining PD-1 with other agents may improve responses and develop biomarkers. In a current trial that has accrued approximately 80 patients and is looking at immunotherapy as a single or double antibody, he and his team are finding that different immunotherapies use various pathways and mechanisms to arrive at the same destination—getting the immune system’s cells to a similar final activity level. “The neoadjuvant approach is helping us obtain a really sophisticated and elegant insight into the tumor microenvironment where there are 30-40 cell populations being modulated and interacting in a way that we would not understand without this approach,” Dr Ferris says.

In October 2024, Dr Ferris took on a new position as the executive director of the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center and as the UNC system chief of oncology services. It is his first career change away from the University of Pittsburgh Medical Center (UPMC), where he established himself as a physician–scientist in immunotherapy in 2001. Beginning in 2017, he served as director and associate senior vice-chancellor for cancer research at the UPMC Hillman Cancer Center, and he was a founding codirector of the Tumor Microenvironment Center. Under his leadership, the center obtained or renewed three National Cancer Institute (NCI) Specialized Program of Research Excellence research grants in head and neck, skin, and ovarian cancers and multiple principal investigator grants. This, in turn, spurred a 29% increase in peer-reviewed cancer research funding and a 53% increase in NCI funding.

His return to UNC is a homecoming of sorts. He earned his undergraduate degree in chemistry at UNC, where he completed an honors thesis in blood clotting and thrombosis. From there, he moved to Baltimore, Maryland, where he earned his medical degree and PhD in immunology from Johns Hopkins Medical School. This is where he also completed his residency in otolaryngology and head and neck surgery. He chose to specialize in head and neck cancers via his initial interest and doctoral work in the immunology of HIV as a PhD student; his laboratory work focused on developing an HIV vaccine. That training transferred “beautifully,” he says, to working on how the immune system recognizes cancer antigens that are handled similarly to virus antigens, just as a viral etiology was being identified in head and neck cancer.

He calls it a “natural bridge” to then apply his immunology training to head and neck cancers in view of the discovery, during the same time and at the same institution (Johns Hopkins Medical School), of the connection between human papillomavirus (HPV) and head and neck cancer through the work of Maura L. Gillison, MD, with whom Dr Ferris later collaborated on the CHECKMATE 141 trial.

During Dr Ferris’ ongoing work in HPV-related head and neck cancer research, he has served as the lead investigator of two prospective randomized trials. One examined the potential for surgical intensification via a reduced radiation dose in patients with HPV-positive oropharyngeal cancer treated with transoral robotic or laser surgery (ECOG 3311). The second used a molecular biomarker of “high-risk” HPV-negative cancer to compare adjuvant radiation alone with a combination of cisplatin and radiation in patients with disruptive or nondisruptive p53 alterations (ECOG–ACRIN 3132).

Dr Ferris will continue his funded research from the National Institutes of Health and clinical practice at UNC, but most of his time will be devoted to his leadership role in developing and overseeing the Lineberger Comprehensive Cancer Center. He also hopes to launch and lead a comprehensive oncology service line across the Research Triangle and eventually the entire state of North Carolina for the UNC health system.

Dr Ferris’ career path has been forged by unexpected twists and serendipitous turns that accompany and often govern high achievement. The twist from HIV to cancer came in the early 1990s and was fueled by his strong interest in immunology. “When I look back on it, somebody would have to be crazy to throw their career at something that did not work,” he says, referring to the sentiment at the time within oncology about immunotherapy. However, he made the leap of faith, and now 30 years later, immunotherapy “is truly the fourth modality and has improved survival outcomes and quality of life” in patients with cancer, he says.

The serendipitous turn came with the discovery of HPV-related head and neck cancers at the same time and institution where Dr Ferris decided to switch from virus-focused immunology to cancer-focused immunology. “I think luck does favor the prepared mind,” says Dr Ferris.

Returning to his alma mater in UNC, Dr Ferris finds it “surreal” to be back. In another chance turn, he will be hosting the 35th reunion of the UNC class of 1990, of which he was class president, at the same time as UNC will be playing the University of Pittsburgh.

Ever the diplomat, he intends to keep his cheering neutral but, as he did in Pittsburgh, will wear a Pittsburgh T-shirt and a UNC hat and switch them at halftime.