A Study of SER-155 to Treat Diarrhea in People on Immunotherapy

Inclusion Criteria:

• Age > 18 years

• Receipt of ICI (single-agent or combination) within the 180 days precedingscreening.

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 abovebaseline during the screening window), deemed by the treating provider as likelyrelated 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 ofcontraception (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, andunderstand the potential risks and benefits of study enrollment and treatment.

Exclusion Criteria:

• Active GI infection, including untreated viral, bacterial or fungal cause(s) ofdiarrhea.

• Received immunosuppressive therapies for suspected or confirmed irEC, includingsystemic corticosteroids (either oral or intravenous) and/or infliximab, vedolizumabor 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 ofscreening

• 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 antibacterialantibiotics

• Severe neutropenia, as defined by an absolute neutrophil count (ANC) < 500cells/mm^3, at time of screening

• Treatment with investigational medications used for diarrhea/colitis treatment andmicrobiome 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 studyparticipation and/or may interfere with the interpretation of study results