Rapid Research Autopsy Trial leads to new precision cancer medicine treatments
A Pelotonia-funded Rapid Research Autopsy Trial that is helping OSUCCC – James scientists understand why certain cancers spread and evolve by studying tissues collected within hours of a patient’s death is guiding therapies in a new clinical trial for current patients. Principal investigator for both studies is Sameek Roychowdhury, MD, PhD, whose lab team discovered through its Rapid Research Autopsy Trial— launched in 2016—that FGFR gene mutations (alterations) can affect whether a patient’s tumor responds to targeted therapies.
The team has developed a phase II clinical trial that examines how well a drug called infigratinib works in treating solid tumors that have spread to other places in the body in patients with FGFR gene mutations. All patients involved in the study have FGFR gene mutations, but their cancers manifest in different parts of the body. The drug infigratinib may stop the growth of these tumor cells by blocking FGFR proteins in the tumors. “This way of looking at cancer, called precision cancer medicine, reveals potential treatment options based on specific molecular features of a cancer versus disease site. This is a radically different way to target therapy that has the power to produce more effective treatments for our patients,” Roychowdhury says.
To monitor how well patients are responding to treatment, this trial is supported by another Pelotonia-funded Idea Grant that Roychowdhury received in 2019 titled “Liquid Biopsy for Rapid Detection and Real Time Monitoring of FGFR-Altered Cancers.” This Idea Grant has led to a new grant from the NCI to develop a blood test to monitor FGFR gene mutations in the blood. One patient who has benefited from this work is Pam Matthews. When an ultrasound revealed uterine cancer, she was referred to a gynecologic oncologist in Cincinnati for a hysterectomy followed by chemotherapy and radiation. The treatment kept the cancer from advancing for about six months before she developed a secondary cancer in her lungs that required surgery. Despite trying numerous treatment options, including a clinical trial in Cincinnati, Matthews kept experiencing cancer recurrence. Her Cincinnati oncologist, Paula Weisenberger, MD, referred her to the OSUCCC – James for a trial led by gynecologic oncologist David O’Malley, MD. She joined a new trial, but the cancer persisted. Then in April 2020, she met Roychowdhury and learned about his team’s phase II clinical trial that gave her access to a new oral drug therapy that targeted her tumor’s mutation in the FGFR (fibroblast growth factor receptor) gene. More than a year-and-a-half out from her initial clinical trial treatment, Matthews has stable tumors, and no additional tumors have developed. The clinical trial that is helping Matthews and others reflects the value of the Rapid Research Autopsy Trial.
Study seeks to understand effectiveness of COVID-19 vaccination in cancer patients, survivors
A large study at the OSUCCC – James is evaluating how vaccination against SARS-CoV-2, the virus that causes COVID-19, impacts the immune system of cancer patients. Project leaders believe the study—supported by funds from Pelotonia and the OSUCCC – James—will advance the scientific community’s understanding of how effective the SARS-CoV-2 mRNA vaccine is in preventing COVID-19 infection, determine whether the vaccine is less effective in cancer patients receiving certain therapies and shed light on how long immunity lasts. Many cancer therapies impact the immune system, which can leave it temporarily or permanently more susceptible to infection.These therapies could result in higher susceptibility to infection, more severe infection and a higher chance of death from COVID-19 infections.
Co-principal investigators for the study, which is known as SIIREN (Study of Infections and Immune REspoNse), are Peter Shields, MD, deputy director of the OSUCCC – James, and Zihai Li, MD, PhD, director of the Pelotonia Institute for Immuno-Oncology (PIIO) at the OSUCCC – James. When the study began, the researchers noted that there was no peer-reviewed published data on how cancer therapy affects the efficacy of the COVID-19 mRNA vaccine because cancer patients receiving active therapy were excluded from vaccine trials. “This is a complicated study that our team developed in record time; from concept to our first patient was about eight weeks,” says Shields, a professor in the Division of Medical Oncology at Ohio State and member of the Cancer Control Program at the OSUCCC – James. “This was hard work from more than 20 faculty and staff who were wellsupported by leadership at all levels. Special credit also goes to the Ohio State Wexner Medical Center vaccine staff at the Schottenstein Center who made this happen with no slow-downs for overall vaccine patient flow.” “Our study will provide data to confirm how effective the current COVID-19 vaccines are for preventing infection and transmission to others, which is a critical public health and economic question, especially for this high-risk population. It is also one of the largest prospective clinical trials to examine the immune response of cancer patients to the COVID-19 mRNA vaccines,” says Li, a professor in the Division of Medical Oncology at Ohio State and member of the Translational Therapeutics Program at the OSUCCC – James.
Researchers will enroll up to 450 cancer patients and 100 healthy volunteers aged 18 or older who are undergoing COVID-19 vaccination at the Ohio State Wexner Medical Center. The investigators will focus on how infection susceptibility and immunity change, based on each patient’s stage of disease and treatment regimen. “Getting shots in arms to reach herd immunity so that—as a country—we can get back to some sense of normalcy is critical,” Shields says. “Science has helped us rapidly mobilize to develop COVID-19 vaccines that are safe and effective at reducing severe illness and death in the adult general population, but there are substantial knowledge gaps we need to fill to provide the best protection to higher-risk populations, including the more than 17 million cancer survivors in the United States.” To learn more about participating in the SIIREN study, visit cancer.osu.edu/SIIREN.