Probiotics for the Prevention of Immunotherapy Induced Colitis in Patients Receiving Immunotherapy

Inclusion Criteria:

• Male or female age ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

• Histologically confirmed solid malignancy

• Will be starting on ICIs

• For cohort 1: Ipilimumab with or without anti-PD-1/PD-L1 including but notlimited to pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, ordurvalumab

• For cohort 2: Anti-PD-1/PD-L1 described above with or without chemotherapy

• Absolute neutrophil count (ANC) ≥ 1000/mm^3

• Platelet count ≥ 75,000/mm^3

• Hemoglobin ≥ 9.0 g/dL

• Creatinine ≤ 2 x upper limit of normal (ULN)

• Serum glutamic-oxaloacetic transaminase (SGOT) [aspartate transaminase (AST)] ≤ 2 xULN

• Albumin ≥ 3 g/dL

• Willing and able to provide research stool and blood samples

• Negative serum pregnancy test done ≤ 7 days prior to enrollment, for women ofchildbearing potential only

• Capable of providing valid informed consent

• Willing to return to enrolling institution for all study visits (blood draws, etc)

Exclusion Criteria:

• Requires prolonged systemic antibiotic therapy for other condition and recentsystemic antibiotic within the past 2 weeks

• Fecal microbiota transplant (FMT) within the past 6 months

• FMT with an associated serious adverse event related to the FMT product or procedure

• Co-morbid systemic illnesses or other severe concurrent disease which, in thejudgment of the investigator, would make the patient inappropriate for entry intothis study or interfere significantly with the proper assessment of safety andtoxicity of over-the-counter probiotics

• Immunocompromised patients including patients known to be HIV positive or those onchronic steroids > 20 mg prednisone a day or prednisone-equivalent Note: Must be offsystemic steroids at least 90 days prior to enrollment. However, topical steroids,inhalants or steroid eye drops are permitted

• History of inflammatory bowel disease (IBD), e.g., ulcerative colitis, Crohn'sdisease, or microscopic colitis

• History of chronic diarrhea

• History of celiac disease

• Currently has a colostomy

• Intraabdominal surgery related to gastrointestinal tract within the last 60 days

• Evidence of active, severe colitis

• History of short gut syndrome or motility disorders

• Requires the regular use of medications to manage bowel hypermotility

• Active autoimmune disease that has required systemic treatment in the ≤ 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressivedrugs) prior to randomization. Note: Replacement therapy (e.g., thyroxine, insulin,or physiologic corticosteroid replacement therapy for adrenal or pituitaryinsufficiency) is not considered a form of systemic treatment. Patients withvitiligo, Graves' disease, or psoriasis not requiring systemic treatment within thepast 30 days are not excluded