A new collaboration between two Western New York cancer research leaders will help oncologists learn whether Black and white cancer patients respond differently to a game-changing immunotherapy treatment. It seeks to improve the safety and effectiveness of these newer drugs in diverse populations.
Funded by a two-year, $2.08 million grant from the National Cancer Institute (NCI), with the possibility of additional funding after the initial phase of the project concludes, the UR Medicine’s Wilmot Cancer Institute , and Roswell Park Comprehensive Cancer Center are working together to fill a major gap in the science around immune checkpoint inhibitors (ICIs).
Checkpoint inhibitors — such as nivolumab (Opdivo) and pembrolizumab (Keytruda) — have become standard care for 16 different types of cancer, both early and advanced-stage. They work by blocking signals in the immune system, clearing a path for the body’s natural T cells to kill cancer. Since their approval in 2011, the use of these drugs has skyrocketed and is believed to be partly responsible for a significant drop in U.S. cancer deaths.
Still, there are many opportunities to improve the care of patients who may benefit from ICIs. For example, few people of African ancestry participated in the original clinical trials to evaluate these treatments. Researchers plan to collect data to investigate side effects, toxicities, and outcomes among people of African ancestry who take immune checkpoint inhibitors.
“Our project is designed to get the full 360 picture of Black patients who receive immunotherapy,” said Co-Principal Investigator Charles Kamen, Ph.D., M.P.H., assistant professor of Surgery and a member of Wilmot’s Cancer Prevention & Control research program. “Not only are we measuring their response to treatment, but we’re also looking at factors like discrimination by providers and health care systems and how often treatment is stopped, so that we have a better understanding of equity and access to high-quality care.”
The project is the first large, national study of diverse patients treated with ICIs.
Gary Morrow, Ph.D., M.S., dean’s professor of Surgery at the University of Rochester Medical Center and another co-investigator on the project, will work with the team to leverage Wilmot’s position as a hub for the National Community Oncology Research Program (NCORP). Morrow is co-principal investigator for the NCORP program, which is supported by a $29 million NCI grant. The NCORP network provides access to hundreds of community oncology clinics in the U.S., where researchers can carry out the immune checkpoint study. The team also plans to enroll study participants in Western New York.
The trial, known as the DiRECT Cohort, will seek to enlist 600 Black patient volunteers and 1,200 white cancer patients of European ancestry.
“The National Cancer Institute Community Oncology Research Program (NCORP) Research Base we have had at Wilmot for three decades is ideally suited to help direct a large often nationwide study like this,” Morrow said. “We’re eager and proud to actively participate in this important research with our longtime colleagues and friends from Roswell.”
The research builds off discoveries from Roswell Park that helped to explain why standard treatments are less effective in patients of African ancestry.
“Checkpoint inhibitors have largely not been studied in Black cancer patients, but our recent findings show that there may be a particular benefit to these immunotherapies for cancer patients of African ancestry — across a variety of cancer types,” says Christine Ambrosone, Ph.D., Chair of Cancer Prevention & Control at Roswell Park and a co-investigator on the study.
Researchers will conduct genetic analyses, for example, of the percent African ancestry in each Black patient, as well as social determinants of health, such as access to healthcare, as a predictor of treatment response and toxicities. They will also evaluate treatment delays due to severe side effects, and the short- and long-term treatment outcomes.
“Because Black cancer patients tend to have a prevalence of what we call ‘exhausted,’ nonfunctional T cells, we realized they may be more likely to do well on immune checkpoint inhibitors, which target the exhausted T cells to revive them and restore their ability to fight cancer cells,” said Song Yao, Ph.D., professor of Oncology at Roswell Park and co-principal investigator on the study. “But we can’t know this without further study, and this new project will tackle that knowledge gap in a large and diverse patient population.”