Role of Gut Microbiome and Fecal Transplant on Medication-Induced GI Complications in Patients With Melanoma or Genitourinary Cancer

PRIMARY OBJECTIVES:

I. To compare the difference in stool microbiome pattern between patients who develop
immune-checkpoint inhibitor (ICPI)-related colitis and patients who don't develop
ICPI-related colitis.

II. To compare the difference in stool microbiome pattern in patients who developed
ICPI-related colitis before and after colitis medical treatment.

SECONDARY OBJECTIVES:

I. To identify and characterize immune profile and genetic factors associated with onset of
ICPI-related colitis in blood and colon tissue.

II. To identify and characterize immune profile and genetic factors in blood and colon tissue
that are associated with quick response of ICPI-related colitis to medical treatment.

III. To characterize the endoscopic and histologic features of ICPI-related colitis before
and after medical treatment.

IV. To assess stool microbiome features that are associated with good response to fecal
microbiota transplantation.

V. To assess the factors in genetic/immune profile obtained from blood and colon tissue that
are associated with good response to fecal microbiota transplantation.

VI. To characterize the endoscopic and histologic features of ICPI-related colitis before and
after fecal microbiota transplantation.

VII. To assess the adverse events related to fecal microbiota transplantation.

EXPLORATORY OBJECTIVES:

I. To identify and characterize immune profile and genetic factors associated with onset of
ICPI-related colitis in inflamed colonic mucosa and its matched normal mucosa.

II. To characterize the immune profile and genetic factors from the colon tissue in these
colitis patients among different histological subtypes.

III. To assess the pattern of stool microbiome that is associated with good tumor response to
ICPI treatment.

IV. To assess the association between stool inflammatory markers (i.e. lactoferrin and
calprotectin) and the severity of endoscopic/histologic inflammation.

V. To assess the sensitivity and specificity of stool inflammatory markers (i.e. lactoferrin
and calprotectin) as an indicators of ICPI-relate colitis response to treatment.

VI. To assess the microbiome pattern that triggers the infections on immunosuppressant
treatment for ICPI colitis.

OUTLINE:

PROJECT 1: Patients receive standard of care and undergo collection of stool and blood
samples.

PROJECT 2: Patients receive prednisone, infliximab, or vedolizumab per standard of care and
undergo standard of care endoscopy 2 months after treatment. Patients also undergo collection
of stool, blood, and tissue samples.

PROJECT 3: Patients undergo fecal microbiota transplant (FMT).

After completion of study, patients are followed up periodically.

Inclusion Criteria:

- Diagnosis of any stage melanoma or genitourinary (GU) malignancies.

- Treatment with any ICPI agent.

- Ability to understand and willingness to sign an informed consent form.

- Life expectancy > 4 months.

- PROJECT 1: ICPI-related diarrhea/colitis of any grade with or without concurrent non
GI toxicity as the toxicity group.

- PROJECT 1: Patients with no organ toxicity as the control group.

- PROJECTS 2 AND 3: ICPI-related colitis of grade 2 or above as GI toxicity without
involvement of non GI toxicity.

- PROJECT 3: ICPI-related colitis with ANY of the following characteristics: (1)
refractory to treatment of steroid and two doses of non-steroidal immunosuppressants
e.g. infliximab and/or vedolizumab; (2) contraindication for immunosuppressive
treatment; or (3) recurrence after successful initial treatment.

Exclusion Criteria:

- Positive GI infection at the onset of ICPI-related GI toxicity.

- History of inflammatory bowel disease, and/or radiation enteritis or colitis.

- Pregnant and breastfeeding women.

- Women of child-bearing potential who have positive urine or serum pregnancy test or
refuse to do pregnancy test.

- PROJECT 2: Patients who have a contraindication for immunosuppressive treatment.

- PROJECT 2: Patients who develop concurrent or only non GI toxicity.

- PROJECT 3: Patients with active bacterial or fungal infection.