Cancer immunotherapy has revolutionized the treatment of patients living with melanoma. It unleashes the immune system to recognize and kill melanoma cells, improving patients’ lives. These drugs are now the standard of care ifor melanoma patients. Despite these new medicines, melanoma remains the leading cause of skin cancer-related deaths in Canada, and more than 50% of patients treated with immunotherapy experience melanoma progression. Finding new ways to enhance the immune system and improve the benefits of immunotherapy is therefore an urgent unmet need.
Researchers in Montreal and Toronto have shown that the trillions of bacteria living within the human gastrointestinal system, known as the gut microbiome, could be essential for a melanoma patient to respond to immunotherapy. An increasing body of research demonstrates the significance of having a healthy gut microbiome before starting immunotherapy. As a result, efforts are focused on finding safe methods to alter the gut microbiome to improve the potential benefits of immunotherapy.
Thus far, the most extensively studied and direct method to change the gut microbiome is through a fecal transplant, also known as a fecal microbiota transplantation. Fecal transplant is approved for the treatment of patients with severe infection of the large bowel that do not respond to antibiotics. Stool from healthy donors is transplanted into the patient by processing the feces of a healthy donor and making capsules for the patient to swallow. The capsules are triple-encapsulated and are completely odourless and tasteless. The night before the transplant, the patient must complete bowel preparation by drinking fluids to flush out the microbiome. This is important to prepare the patient’s gut to eliminate harmful bacteria and create an environment for good bacteria to thrive.
The transplant is performed under the direct observation of research staff one week prior to the first immunotherapy treatment. This technique has been studied in mouse cancer models and in patients with melanoma and other cancers treated with immunotherapy, yielding promising results. Three studies have shown that performing a fecal transplant before initiating immunotherapy treatment is safe, and more patients experience shrinkage of their melanomas compared to results from previous immunotherapy studies.
Based on these preliminary findings, a larger randomized trial is being planned to determine if a fecal transplant before starting immunotherapy can control (reduce the risk of progression) melanoma longer compared to standard-of-care immunotherapy. Capsules will be administered and prepared from healthy donors using a Health Canada-approved healthy donor screening and capsule preparation program. The clinical trial plans to enroll 128 patients with advanced melanoma who have not previously received immunotherapy. Half of the patients will be randomized to receive a fecal transplant in addition to standard immunotherapy, while the other half will receive standard immunotherapy alone. Researchers will also collect stool samples from both groups and analyze connections between the gut microbiome and response at different time points.
This study would be the largest to date testing this method of changing the microbiome for melanoma patients. It will provide insights into how the gut microbiome can be altered and whether this can improve the outcomes for melanoma patients receiving immunotherapy. If results are promising, this trial will inform the design of large, potentially practice-changing phase III randomized controlled trials employing the microbiome targeting approaches.
We anticipate this trial will start in early 2024, with the clinical trial locations spread widely across Canada. Information will be available on our website, and we will notify you when the trial is recruiting, or you can visit https://www.canadiancancertrials.ca or our Clinical Trail Finder: As always, please speak to your oncologist to determine if this might be appropriate for you.
