Biotherapeutic Shows Benefit in Reducing Immunotherapy-Related Enterocolitis

Treatment with SER-155, a cultivated multi-strain live biotherapeutic, resulted in a high rate of clinical response to diarrhea associated with immune checkpoint inhibitor (ICI)-related entercolitis (irEC), according to topline results from a phase 1b trial.¹

In the investigator-sponsored open-label trial (NCT06801067) at Memorial Sloan Kettering (MSK) Cancer Center, 80% of recipients achieved an immunosuppressive-free clinical response at day 15 in patients with moderate-to-severe irEC.

Unmet Need for Diarrhea Management

ICIs including PD-1/PD-L1 and CTLA-4 inhibitors are used to treat various types of cancers, but irEC affects approximately 25% of all patients receiving immune checkpoint inhibitors (ICI) in the United States and represents a clinically significant management challenge. Current standard of care for immune-related diarrhea may require halting ICI cancer therapy and initiating systemic corticosteroids and/or biologic immunomodulators, which carry risks including systemic immunosuppression, increased infection, metabolic complications, and potential interference with antitumor activity. A nonimmunosuppressive approach that could allow patients to continue ICI therapy represents a substantial unmet need.

SER-155 is an oral live biotherapeutic being investigated to treat disruptive conditions of the gastrointestinal tract. In a previous phase 1b placebo-controlled study (NCT04995653) in patients receiving allogeneic hematopoietic cell transplant, SER-155 showed a 77% relative reduction of bloodstream infections, with evidence of improved intestinal epithelial barrier integrity and modulation of systemic inflammatory responses.²

Trial Design and Patient Population

The phase 1 trial, led by principal investigator David Faleck, MD, of MSK, enrolled 15 patients with grade 2 to 3 irEC who were naive to immunosuppressive therapy. Participants received microbiome conditioning with oral vancomycin on days 1 and 2, followed by 2 daily oral capsules of SER-155 for 12 consecutive days.¹

The primary efficacy end point was the proportion of patients achieving immunosuppressive-free clinical response at day 15, defined as at least a 1-grade improvement in diarrhea symptoms without use of immunosuppressive therapy. Patients in the study were receiving a wide range of ICI types, including PD-1 inhibitors (pembrolizumab [Keytruda], nivolumab [Opdivo], retifanlimab [Zynyz]), PD-L1 inhibitors (durvalumab [Imfinzi], avelumab [Bavencio]), CTLA-4 inhibitors (ipilimumab [Yervoy], tremelimumab [Imjudo]), the LAG-3 inhibitor combination nivolumab/relatlimab (Opdualag), and combinations of these agents.

Efficacy Results

At day 15, 12 of 15 patients (80%) achieved the primary end point of immunosuppressive-free clinical response. Of those 12 responders, 8 (67%) achieved a 2-grade or greater improvement in diarrhea without immunosuppressive therapy. Additionally, 5 of 15 patients (33%) achieved immunosuppressive-free complete clinical remission, defined as total resolution of diarrhea to grade 0, at day 15.

At day 43, 5 of 15 patients (33%) maintained immunosuppressive-free clinical response, and 2 of 15 (13%) maintained immunosuppressive-free complete clinical remission. All 12 patients with immunosuppressive-free clinical response at day 15 had the same or better diarrhea grade at day 43; 7 of the 12 received non–systemically acting gastrointestinal-targeted immunosuppressives after day 15.

Pharmacology and Safety

Fecal calprotectin and fecal albumin, which are translational biomarkers of gastrointestinal inflammation and mucosal epithelial barrier integrity, respectively, were elevated at baseline and showed statistically significant reductions by day 43, supporting SER-155's mechanism of repairing mucosal epithelial barrier function and reducing gastrointestinal inflammation. Bacterial strain engraftment was robust, with kinetics, magnitude, and durability comparable to prior clinical studies.

SER-155 was well tolerated through day 43, with no serious adverse events assessed as related to the study drug and no bloodstream infections reported. Two patients each experienced 2 nonserious adverse events assessed as possibly related to vancomycin and SER-155; all were moderate in severity and resolved.

“These results suggest SER-155 may offer a promising, novel approach to managing irEC, with the potential to reduce reliance on systemic immunosuppressive therapies, while also helping patients continue ICI treatment,” Faleck stated in a news release. He said that full trial results are planned for presentation at a future medical conference.

SER-155 has received breakthrough therapy and fast track designations from the FDA. Seres Therapeutics indicated it is engaging with potential partners to advance a phase 2 study of SER-155 in allogeneic hematopoietic cell transplant and other trials.

REFERENCES

1. Seres Therapeutics announces early clinical data showing potential for SER-155 in immune checkpoint inhibitor-related enterocolitis (irEC), a frequent adverse reaction that forces many patients to halt cancer treatment. News release. Seres Therapeutics. July 8, 2026. Accesed July 9, 2026. https://tinyurl.com/549t3ktx

2. Seres Therapeutics presents expanded SER-155 exploratory biomarker data at 2025 ASCO Annual Meeting. News release. Seres Therapeutics. May 28, 2025. Accessed July 9, 2026. https://tinyurl.com/4729z4ht