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

Inclusion Criteria:

1. Diagnosis of any stage melanoma, Non-Small Cell Lung Cancer or genitourinary (GU)malignancies (Project 1).

2. Diagnosis of any cancer type (Projects 2 and 3)

3. Treatment with any ICPI agent

4. Ability to understand and willingness to sign an informed consent form and ratesurveys

5. Life expectancy > 4 months (Project 3)

6. ICPI-related diarrhea and/or colitis of any grade with or without concurrent non- GItoxicity as the toxicity group (project 1)

7. Patients with no organ toxicity as the control group (project 1)

8. ICPI-related colitis and/or diarrhea of grade ≥ 2 as GI toxicity (initial episode orrecurrence) receiving standard treatment of immunosuppressive agents (steroid,infliximab, vedolizumab, or ustekinumab) any time during the colitis disease courseuntil sustained resolution of GI toxicity, or one- year time point after enrollment (Project 2)

9. ICPI-related colitis and/or diarrhea of grade ≥ 2 as GI toxicity without involvementof non- GI toxicity within 45 days prior to FMT (Project 3)

10. ICPI-related colitis and/or diarrhea of grade ≥ 2 within 45 days prior to FMT withANY of the following characteristics (project 3):

(i) refractory to treatment of steroid and two doses of non-steroidalimmunosuppressants e.g. infliximab, vedolizumab or ustekinumab,

(ii) contraindication for immunosuppressive treatment,

(iii) recurrence after successful initial treatment,

(iv) recurrent symptoms once steroid is tapered down/off or diarrhea/colitissymptoms are steroid dependent, or

(v) patients with a history of refractory ICPI-related colitis and/or diarrhea tomedical treatment, even if they have improved symptoms from supportive care within 45 days prior to FMT

11. No concern for active concomitant GI infection for the ICPI diarrhea/colitis work upat the time of protocol therapy initiation as confirmed by stool tests or as per thetreating physician based on clinical presentation (project 3)

12. Patient who has been cleared for enrollment by Infectious Diseases consultant ortreating physician if positive infection workup or screening tests (e.g. lifelongpositive T-spot due to BCG inoculation, chronic colonization) prior to initiation ofdiarrhea/colitis treatment (project 3)

Exclusion Criteria:

1. Age younger than 18 years

2. History of inflammatory bowel disease, and/or radiation enteritis or colitis withactive disease status at the time of study treatment initiation

3. Pregnant and breastfeeding women

4. Women of child-bearing potential who have positive urine or serum pregnancy test orrefuse to do pregnancy test unless last menstrual cycle was > 1 year prior toconsent and/ or clear documentation states that patient is peri- or post-menopausalor there was recent supporting objective evidence of 'no pregnancy' status (e.g.blood or imaging) within 30 days prior to date of study treatment

5. Patients who develop concurrent non- GI toxicity at the time of FMT treatment (project 3)

6. Patients with active bacterial or fungal infection (Project 3)

7. Donors at risk for monkeypox infection and/ or exposure as determined by aquestionnaire (Project 3)

Withdrawal Criteria

1. Patients may withdraw from the trial at any time

2. Patients who develop GI perforation or toxic colitis that require surgery from ICPIcolitis

3. In project 3, if the first 30% of cases fail the fecal transplant treatment, thenproject 3 will be terminated