Cambridge, Massachusetts-based Seres Therapeutics (Nasdaq: MCRB) reported early clinical data suggesting that SER-155, its oral live biotherapeutic, may resolve diarrhea associated with immune checkpoint inhibitor-related enterocolitis without requiring systemic immunosuppression — a finding that, if confirmed in larger studies, could address one of the more clinically consequential adverse reactions limiting cancer immunotherapy use. The data, from a 15-patient Phase I investigator-sponsored trial conducted at Memorial Sloan Kettering Cancer Center, showed that 80% of participants achieved an immunosuppressive-free clinical response at Day 15, the primary endpoint.
In the single-arm Phase I study, 12 of 15 patients (80%) achieved the primary endpoint of at least a one-grade improvement in diarrhea without systemic immunosuppression by Day 15, while one-third achieved complete remission. Biomarkers of gastrointestinal inflammation also improved, and no serious treatment-related adverse events were reported.
The trial was single-arm and open-label, enrolling 15 patients at a single center, which substantially limits interpretation. The absence of a control arm means the observed response rates cannot be attributed to SER-155 with certainty, and the small sample size precludes conclusions about durability or patient subgroup effects. The study was sponsored by Memorial Sloan Kettering rather than Seres, and is designed as an exploratory study to inform further development rather than as a registration-enabling trial. Efficacy data beyond Day 43 were not reported.
SER-155 is a defined, cultivated multi-strain bacterial consortium administered orally; it is designed to engraft in the gastrointestinal tract and restore microbiome homeostasis, targeting mucosal epithelial barrier integrity and immune regulation at the gut-immune interface. Current standard of care for moderate-to-severe irEC requires halting checkpoint inhibitor therapy and initiating systemic corticosteroids, with infliximab (Remicade) or vedolizumab (Entyvio) used in steroid-refractory cases. Both agents carry systemic immunosuppressive effects that may blunt anti-tumor immunity — a concern that underpins the rationale for a microbiome-based approach.