3 NCI grants support expanded collaboration with University of Rochester, Kaiser Permanente Division of Research

Three competitive National Cancer Institute (NCI) grants totaling $13.5 million will support the Roswell Park Comprehensive Cancer Center team leading a multi-institutional effort aimed at improving the potential of immune checkpoint inhibitors (ICIs) — a promising and relatively new type of cancer immunotherapy credited with bringing about the largest decline in cancer deaths in a single year, from 2016-2017. Working in close collaboration with experts from the University of Rochester’s Wilmot Cancer Institute and Kaiser Permanente Northern California Division of Research, Roswell Park will expand on work to understand differences in how cancer patients of different races may respond to common immunotherapies.

Immune checkpoint inhibitors work by “releasing the brakes” on the immune system to mount a stronger attack against cancer. The FDA approved the first ICI in 2011, and today they have become the standard of care for more than 20 types of cancer.

“Immune checkpoint inhibitors can make some very lethal cancers more manageable, so patients survive longer,” says Song Yao, MD, PhD, Vice Chair and Professor of Oncology in the Department of Cancer Prevention and Control at Roswell Park.

But not all patients benefit equally, and it’s not clear why. Very limited data exist on how minoritized racial and ethnic groups — including Black Americans — do on ICI therapy. Two years ago, Roswell Park and the University of Rochester’s Wilmot Cancer Institute took the first step toward answering those questions with a prospective study, the Disparities in REsults of immune Checkpoint inhibitor Treatment (DiRECT) Cohort. The DiRECT Cohort aims to find out whether Black and white cancer patients respond differently to ICIs and whether the drugs’ safety and effectiveness can be improved for all populations.

“We hope our findings can provide information about how Black patients are doing with these new treatments, because we really don’t have a lot of data,” says Dr. Yao. “Our hypothesis is that people of African ancestry may particularly benefit from immune checkpoint inhibitors, and if that’s true, these drugs may help reduce cancer health disparities.”

In 2021 the NCI awarded the partner institutions a UG3 grant to determine the feasibility of the study, with additional funding contingent on their progress toward enrolling a total of 1,800 cancer patients, including 1,200 white patients and 600 Black patients.

“We have enrolled 1,100 patients after one and half years, which is fantastic progress. We’re enormously grateful to all those who’ve opted to participate in this work,” notes Charles Kamen, PhD, Associate Professor of Surgery and Psychiatry at Wilmot, who, with Dr. Yao, co-leads the DiRECT Cohort as a multiple principal investigator.

Details on the three new NCI grants and the work they will enable:

A UH3 grant of $9,567,094 for the second, research-focused phase of the DiRECT Cohort, which will collect data on patient response to ICIs given either as a monotherapy or in combination with other cancer therapies.

Gary Morrow, PhD, MS, a Dean’s Professor of Surgery at Wilmot Cancer Institute, serves as a senior investigator, Roswell Park’s Christine Ambrosone, PhD, Senior Vice President for Population Sciences and Chair of the Department of Cancer Prevention and Control, is senior investigator and Lori Sakoda, PhD, Research Scientist with Kaiser Permanente Northern California Division of Research, serves as the subcontract principal investigator. Dr. Morrow is also co-principal investigator for the National Community Oncology Research Program (NCORP), which will enable the team to conduct the study at hundreds of community oncology clinics in the nationwide NCORP network. Through the participation of study co-investigator and clinical co-chair Igor Puzanov, MD, MSci, FACP, Senior Vice President of Clinical Investigation at Roswell Park, cancer patients at member sites in the Roswell Park Care Network also will have access to the study.

With an administrative supplement award of $150,000 from the NCI, investigators will survey patients enrolled in the DiRECT Cohort study about their use of cannabis/cannabinoids.

“That has become a common way for patients to deal with pain, insomnia and stress after a cancer diagnosis and treatment,” says Danielle Smith, PhD, MPH, Assistant Professor of Oncology at Roswell Park, who co-leads this supplement project with Luke Peppone, PhD, Associate Professor at Wilmot. “But some evidence suggests that cannabis use can compromise response to immune checkpoint inhibitor therapy. We hope these questions will help us better understand the prevalence of cannabis use among these patients and how it impacts their treatment response. Our DiRECT Cohort is the perfect platform to look at this question.”

An NCI R01 grant of $3,860,785 will fund a multi-institutional study, Advanced cancer Survivorship after Checkpoint inhibitors: ExamiNing Durable responses (ASCEND), which will examine the physical and psychological challenges of patients with metastatic cancer who have survived a year or more after treatment with ICIs.

“Patients with stage 4 metastatic cancer are living longer with ICIs,” explains Dr. Sakoda. “It is important that we learn more about the challenges they face, and the long-term side effects they may experience, so that we can finds ways to intervene and improve their quality of life.”

That study, which aims to enroll 1,200 people with lung cancer, kidney cancer or melanoma over four years, will be directed by multiple principal investigators: Dr. Kamen at the University of Rochester; Dr. Sakoda at Kaiser Permanente Northern California Division of Research; and Dr. Yao at Roswell Park.