Seres Therapeutics (MCRB) Study result summary

Study background and unmet need

• Immune checkpoint inhibitor-related enterocolitis (irEC) is a serious complication affecting about 25% of patients on immune checkpoint inhibitors, often requiring immunosuppressive therapy that interrupts cancer treatment and increases infection risk.

• Current standard of care involves systemic corticosteroids or immunosuppressants, which carry significant side effects and may compromise anti-cancer efficacy.

• There is a significant unmet need for non-immunosuppressive therapies to manage irEC and allow patients to continue ICI therapy.

Study design and patient population

• Investigator-sponsored, open-label phase I-B trial at Memorial Sloan Kettering Cancer Center enrolled 15 participants with moderate to severe (Grade 2 or 3) irEC who had not received prior immunosuppressive therapy.

• Participants had a range of underlying cancers and prior ICI regimens, with most at advanced stages; most had stage 3-4 disease and 60% had severe Grade 3 diarrhea at entry.

• Treatment involved 2 days of vancomycin conditioning followed by two oral SER-155 capsules daily for 12 days.

• The primary endpoint was immunosuppressive-free clinical response at Day 15, defined as at least a one-grade improvement in diarrhea without corticosteroids or biologics.

Efficacy results

• 80% (12/15) achieved immunosuppressive-free clinical response at Day 15; 33% (5/15) achieved complete clinical remission (Grade 0 diarrhea) without immunosuppressive therapy.

• Most responders showed improvement by Day 8, with 67% of responders improving by two or more grades by Day 15.

• All Day 15 responders maintained or improved their response by Day 43; some required only GI-targeted, non-systemic immunosuppressives.