Treatment of Immune Checkpoint Inhibitor-related Diarrhea and/ or Colitis With Ustekinumab in Cancer Patients

Primary Objectives:

To assess the efficacy of ustekinumab for clinical remission/response of immune-related diarrhea and/or colitis

To assess the efficacy of ustekinumab in reducing fecal calprotectin levels

Secondary Objectives:

To assess steroid free IMDC remission by week 4 and 8

To assess the IMDC recurrence by week 4 and 8

To assess the time duration to IMDC recurrence and overall survival

To assess the efficacy of ustekinumab to achieve endoscopic remission of immune-related diarrhea and/or colitis

To identify immune signatures related to GI irAEs and those specific to responsiveness to ustekinumab

To identify pro-inflammatory immune signatures in serum

To assess patient symptom and QOL

Inclusion criteria

• Patients who receive any type of ICI therapy
• Patients with ≥ grade 2 immune-related diarrhea and/or colitis according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 within 45 days prior to enrollment in study
• Patients with ability to understand and willingness to sign informed consent
• Patients with a diagnosis of any type of solid tumors on ICI systemic therapy
• No concern for active concomitant GI infection for immune-related diarrhea and/or colitis work up at the time of protocol therapy initiation as confirmed by stool tests or as per the treating physician based on clinical presentation
• Patient who has been cleared for enrollment by Infectious Diseases consultant or treating physician if positive infection workup or screening tests (e.g. lifelong positive T- spot due to BCG inoculation, chronic colonization) prior to initiation of diarrhea/colitis treatment and/ or imaging (e.g. CXR, CT CAP etc) confirms the absence of active infections (e.g. TB) within 60 days prior to initiation of protocol therapy
• Concurrent or prior cancer therapy (non-checkpoint inhibitors) that are not deemed as a significant contributor of the GI adverse event can be allowed in the study.
• Patients can be on the steroid treatment within 45 days before Ustekinumab
• Patients with non- GI immune-related adverse events (irAEs) can be enrolled if there is no contraindication to the use of ustekinumab in the treatment of the non-GI irAEs present
• Patients with a new index event of . grade 2 immune-related diarrhea and/or colitis may be enrolled if previous IMDC event was . 1 year ago with successful treatment and clinical remission

Exclusion criteria

• Patients younger than 18 years of age
• Patients with persistent gastrointestinal infection confirmed with positive testing despite completing 5 days of antibiotics
• Patients with history of inflammatory bowel disease and/or radiation enterocolitis with active disease status at the time of study treatment initiation
• Pregnant and breastfeeding women
• Women of child-bearing potential who have positive urine or serum pregnancy test or refuse to do pregnancy test unless last menstrual cycle was > 1 year prior to consent and/ or clear documentation states that patient is peri- or post-menopausal or there was recent supporting objective evidence of 'no pregnancy' status (e.g. blood or imaging) within 30 days prior to enrollment in study
• Patients who develop concurrent non-GI toxicity (irAEs) at the time of study treatment initiation, with contraindication to the use of ustekinumab in the treatment of the non GI irAEs present
• Patients have already received other biologic treatment for IMDC such as infliximab, vedolizumab, EXCEPT if these drugs were used in a previous IMDC event that occurred ≥ 1 year earlier at which time there was complete resolution of the disease