Fecal Transplants with Immunotherapy Extend Survival in Advanced Melanoma Patients

Patients with advanced melanoma who received fecal microbiota transplants using healthy donor stool alongside standard immunotherapy survived more than four years, according to final results from an early phase 1 trial.

The research, led by John Gordon Lenehan, M.D., and Saman Maleki Vareki, Ph.D., both of Western University and published in the Journal for ImmunoTherapy of Cancer, followed 20 patients with stage III or IV melanoma and who had not received prior immunotherapy for advanced disease. Participants received a single oral fecal transplant followed by standard immunotherapy with either Opdivo (nivolumab) or Keytruda (pembrolizumab). Treatment continued for up to 24 months.

The median overall survival was 53 months, and the median progression-free survival was 30 months. At the time of data analysis, eight patients were alive, with the longest at 62 months, and seven remained without disease progression. No patients continued receiving immunotherapy, and only two required additional cancer treatments. The survival outcomes exceeded those seen in randomized trials of immunotherapy alone, where median overall survival ranges from 30 to 40 months.

“The gut microbiome influences the response to [immune checkpoint inhibitors], and microbiome manipulation with oral [fecal microbiota transplantation] capsules in this small cohort was safe and appeared to improve clinical outcomes and possibly avoid primary resistance,” the study authors wrote. “A study is under way to characterize the actual benefit, if present, of this combination therapy.”

Not all patients treated with immune checkpoint inhibitors benefit, and other research has pointed to the role of the microbiome in resistance to checkpoint inhibitors, as well as to the immune-related adverse events.

Other studies have also looked at the impact fecal microbiota transplants can have on cancer patients receiving immunotherapies. A meta-analysis published in BMC Medicine in June 2025 examined 10 studies involving 164 patients with solid tumors and found that combining fecal transplants with immune checkpoint inhibitors resulted in an objective response rate of 43%.

In the melanoma study, the objective response rate was 65%, with four patients achieving complete responses. The one-, two- and three-year estimated survival rates were 95%, 74% and 53%, respectively. The median time patients stayed on treatment was a year, and the median time to response was three months.

Eight patients experienced gastrointestinal side effects specifically related to the fecal transplant, occurring between the transplant and the first immunotherapy dose. All were grade 1 or 2 in severity. These eight patients were all responders to treatment, and they showed significantly better progression-free survival compared to those without fecal transplant side effects: 53 months versus 16 months. The median overall survival for patients with these side effects was 54 months compared to 25 months for those without, although this difference only approached statistical significance.

Microbiome analysis revealed that patients with fecal transplant side effects harbored bacteria associated with favorable responses to immunotherapy. In contrast, patients without these side effects showed higher levels of bacteria linked to poor gut health.

The study authors suggest that mild gastrointestinal side effects following fecal transplant may indicate successful engraftment of beneficial bacteria and immune system activation, potentially contributing to better treatment outcomes.

The organization sponsoring the research, Canadian Cancer Trials Group, is now conducting a randomized phase 2 trial to test whether fecal transplants improve outcomes when combined with various immunotherapy regimens for advanced melanoma. That study will include patients receiving anti-PD1 alone, anti-PD1 plus anti-CTLA-4, or anti-PD1 plus anti-LAG-3, with or without fecal transplant.