The purpose of this study is to find out whether SER-155 may be a safe first treatment that causes few or mild side effects for people due to irEC.

Inclusion Criteria:

• Age > 18 years
• Receipt of ICI (single-agent or combination) within the 180 days preceding screening.

Concurrent treatment with cytotoxic chemotherapy or other tumor-directed agents is permitted.

• Grade 2 - 3 diarrhea (i.e., increase of at least 4 bowel movements a day above baseline during the screening window), deemed by the treating provider as likely related to ICI therapy, with or without concomitant symptoms of grade 1 - 2 colitis (e.g.

abdominal pain, bloody or mucoid stools)

• Able to swallow oral medication
• Individuals of childbearing potential willing to use a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) for 30 days after the last dose of SER-155.
• Willing to provide written informed consent, comply with the protocol, and understand the potential risks and benefits of study enrollment and treatment.

Exclusion Criteria:

• Active GI infection, including untreated viral, bacterial or fungal cause(s) of diarrhea.
• Received immunosuppressive therapies for suspected or confirmed irEC, including systemic corticosteroids (either oral or intravenous) and/or infliximab, vedolizumab or ustekinumab
• Grade 3 colitis symptoms, i.e. severe abdominal pain or peritoneal signs
• Admitted to the hospital for irEC
• Prednisone (or steroid equivalent) dose > 10 mg a day for a non-GI irAE at time of screening
• Pre-existing inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis) or microscopic colitis
• Pregnant or lactating women
• Any condition that requires ongoing prophylactic or therapeutic antibacterial antibiotics
• Severe neutropenia, as defined by an absolute neutrophil count (ANC) < 500 cells/mm^3, at time of screening
• Treatment with investigational medications used for diarrhea/colitis treatment and microbiome therapeutics within 30 days prior to enrollment
• Known allergy or intolerance to oral vancomycin
• Unable to comply with the protocol requirements
• Any condition that in the opinion of the investigator may increase the risk of study participation and/or may interfere with the interpretation of study results

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.