FMT + Nivolumab Shows 20% ORR in 10 ICI-Refractory GI Cancer Patients

This open-label, single-arm, single-center phase I study (NCT04130763) assessed the safety and efficacy of combining fecal microbiota transplantation (FMT) from healthy donors with anti-PD-1 therapy in patients with advanced gastrointestinal (GI) cancer resistant to anti-PD-(L)1 treatment. The study enrolled 10 patients with histologically confirmed, unresectable, or metastatic GI cancers (8 gastric, 2 colorectal) who were refractory to prior anti-PD-(L)1 therapy. The treatment regimen consisted of an initial FMT via 60 oral capsules, followed by a combination phase where maintenance FMT (10 capsules per treatment) was paired with nivolumab at 3 mg/kg every 2 weeks for six cycles. Serial biomarker assessments were performed using fecal and blood samples. Results indicated the combination was well tolerated with no serious adverse events reported. The objective response rate was 20% and the disease control rate was 40%. Clinical benefits were associated with colonization of donor-derived immunogenic microbes and an activated immune status reflected in peripheral immune cell populations. Furthermore, microbial signatures for anti-PD-1 responsiveness were identified and validated in an independent cohort. The study concludes by demonstrating the feasibility and safety of this approach and notes the preliminary efficacy signals and identified microbial signatures generate hypotheses for future trials investigating microbiome-based strategies to enhance immunotherapy efficacy.

When immunotherapy stops working for advanced stomach or colon cancer, patients often have few options left. This small, early-stage study tested a new idea: what if we could 'reset' a patient's gut bacteria to help their immune system fight back? Ten patients whose cancers had become resistant to standard immunotherapy received a transplant of healthy donor gut bacteria, taken in capsule form, alongside continued immunotherapy treatment. The most important finding was that this combination was safe, with no serious side effects reported. In terms of early results, two out of the ten patients (20%) saw their tumors shrink, and four patients (40%) had their disease stop growing for a period. The researchers saw that patients who benefited seemed to have new, helpful bacteria from the donor take hold in their gut, and their blood showed signs of a more active immune system. They also identified specific patterns of gut bacteria linked to a better response to treatment. This is just a first step, but it shows that combining a gut bacteria transplant with immunotherapy is a safe and feasible path to explore for patients who have otherwise run out of effective treatments.