Grant: Project Grant

Cancer immunotherapy (IO) enables immune cells to recognize and kill melanoma cells improving the lives of patients. While IO is now the standard-of-care to treat melanoma, melanoma remains the leading cause of skin cancer-related death in Canada, and most patients with advanced melanoma experience disease progression despite treatment. Finding new ways to improve the benefit of IO is urgently needed. Bacteria in the human gut-the gut microbiota-may contribute to potential IO benefits. Safely changing the gut microbiota to improve the benefit from IO is the focus of our research. The most well-studied way to change the gut microbiome is by transplanting stool from healthy donors and is approved to treat infection of the large bowel that does not respond to antibiotics. This technique has been studied in mice and in patients with melanoma treated with IO with promising results. Three studies, including ours, found that performing a stool transplant before IO was safe and resulted in more patients experiencing shrinkage of their tumors compared to results from previous trials of IO without transplant. Building on this research, we propose a larger 128-patient randomized trial of IO +/- stool transplant to further investigate whether stool transplant prior to IO improves progression-free survival. Patients randomized to transplant consume capsules prepared from stool of healthy donors using a Health Canada-approved process. Capsules will be swallowed by the patient while observed by a healthcare professional one week prior to starting IO. Stool samples will be collected to measure changes in the microbiota to correlate with patient outcomes. Our proposed study would be the largest to date testing whether this method of changing the microbiome improves outcomes of patients living with melanoma receiving IO. If results are promising, they will inform the design of a large, potentially practice-changing phase III randomized controlled trial employing stool transplant.