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