New Clinical Trials Set for Pancreatic Ductal Adenocarcinoma
Clinical researchers at Washington University School of Medicine in St. Louis have been awarded a Specialized Programs of Research Excellence (SPORE) grant from the National Cancer Institute (NCI) to continue clinical trials and research aimed at advancing pancreatic cancer care. Awarded in July 2023, it marks the second time that Washington University researchers at Siteman Cancer Center have received the prestigious grant.
The more recent award — $10.9 million over five years — builds upon research from a previous pancreas cancer SPORE grant, as well as other research conducted at Washington University and adds new therapeutic targets specifically for the treatment of pancreatic ductal adenocarcinoma (PDAC), considered to be the deadliest form of pancreatic cancer. The current survival rate for PDAC is less than 10% after five years.
“We think we can change the outcome of patients with pancreatic cancer with the research and clinical trials happening here at Siteman Cancer Center,” said principal investigator David G. DeNardo, PhD, a Washington University professor of medicine and Siteman Cancer Center research member. He is a leading researcher in the national, multi-institutional effort working to identify more effective pancreatic cancer treatments. “Already, research has contributed to improved survival rates for subsets of pancreatic cancer patients, but we think we can do much better.”
Washington University researchers have recently identified a specific anti-inflammatory drug compound, ATI-450, that disrupts a specific molecule, MK2, known to help tumor cells survive pancreatic cancer chemotherapy treatments. Washington University medical oncologists Kian-Huat Lim, MD, PhD, director of GI Oncology, and Patrick Grierson, MD, PhD, found in those earlier studies that the combination of ATI-450 plus chemotherapy weakened cancer cells, reduced tumor size by more than half, and improved survival rates in an aggressive pancreas tumor mouse model. Equally important, ATI-450 appeared to lower the intestinal damage on mice receiving chemotherapy, which could mitigate side effects such as nausea, diarrhea and colitis for patients.
Three New Clinical Trials
The new SPORE grant supports three clinical trials that get under way later this year and early in 2024. All focus on immunotherapy — how to get a patient’s own immune system to recognize and then attack cancer cells, thereby beating the cancer.
One expands the exciting research into the use of MK2 inhibitors. “We are starting an early Phase 1 clinical trial that combines ATI-450 with already approved FOLFIRINOX chemotherapy in patients with advanced pancreatic cancer,” said Dr. Lim, who is a principal investigator of the new clinical trial along with Gregory Beatty, PhD, a renowned physician-scientist specializing in pancreas cancer care and research at the University of Pennsylvania. Dr. Lim added, “We hope to see that the combination therapy will lead to improve treatment response and show some evidence of anti-tumor immune response. If the results are promising, we will move into Phase II/III trials with introduction of immunotherapeutic agents in the future.”
Another clinical trial will continue the research into the use of neoantigen DNA vaccines and add synthetic long peptide (SLP) vaccines to treat PDAC. Earlier clinical trials found that such vaccines can induce robust immune responses. Ongoing research, led in part by William Gillanders, MD, and Robert Schreiber, PhD, will focus on identifying and eliminating the mechanisms of resistance to such vaccines.
The third clinical trial, overseen by Dr. DeNardo and Katrina Pedersen, MD, will test an innovative strategy to prevent entry of immunosuppressive myeloid cells into the tumor, thereby allowing preservation of T-cell immunity that can be further unleased with checkpoint immunotherapy regimens.
“Yes, these are early phase clinical trials, but they are based on solid and innovative science that have high promise of clinical success,” noted Dr. Lim. “We have a tremendous team of clinicians and researchers who have been studying pancreas cancer for years. The only current approved second-line chemotherapy treatment for pancreatic cancer was developed in part by the research here at Washington University. We have changed practice across the country and strive to do so in the future.”
“Research here at Washington University has the potential to change the outcomes of many patients, both in our area and around the globe,” added Dr. DeNardo. “By increasing our understanding of how this cancer interacts with the immune system, we can improve survival for our patients. For patients who are eligible to participate in these trials, they have access to the latest breakthroughs. We have always had great support from the community to identify and enroll patients in our clinical trials and we are grateful, because their participation every step of the way enables us to move the needle on finding an effective treatment for PDAC.”
To view the list of active clinical trials at Siteman, go to siteman.wustl.edu/clinical-trials.