Ustekinumab for immune checkpoint inhibitor-related diarrhea and colitis in cancer patients

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

This will test whether ustekinumab can control immune-related diarrhea and colitis in adults receiving immune checkpoint inhibitors for solid tumors.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: Ustekinumab, infliximab, vedolizumab, radiation
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06807593 on ClinicalTrials.gov

What this trial studies

This phase 2 interventional trial gives ustekinumab to cancer patients who develop grade 2 or higher immune-related diarrhea or colitis while on immune checkpoint inhibitors. Primary outcomes include clinical remission/response and reduction in fecal calprotectin, with secondary outcomes such as steroid-free remission, recurrence timing, endoscopic remission, patient symptoms and quality of life, and overall survival. The study also collects blood and tissue to identify immune signatures linked to GI immune-related adverse events and response to ustekinumab. The trial is sponsored by M.D. Anderson Cancer Center in collaboration with Janssen and enrolls at MD Anderson in Houston, Texas.

Who should consider this trial

Good fit: Adults with solid tumors receiving any immune checkpoint inhibitor who develop grade 2 or worse immune-related diarrhea or colitis within the past 45 days and who have no active gastrointestinal infection are the intended participants.

Not a fit: Patients whose diarrhea or colitis is due to active infection, non-immune causes, or who have only mild (grade 1) symptoms are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, ustekinumab could reduce GI inflammation from immunotherapy, help symptoms resolve faster, and reduce the need for prolonged steroids that interrupt cancer treatment.

How similar studies have performed: Limited case series and retrospective reports suggest ustekinumab or other IL-12/23 blockers can help steroid-refractory ICI colitis, but large randomized evidence is still lacking.

Eligibility criteria

Inclusion Criteria:

1. Patients who receive any type of ICI therapy
2. 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
3. Patients with ability to understand and willingness to sign informed consent
4. Patients with a diagnosis of any type of solid tumors on ICI systemic therapy
5. 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
6. 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
7. 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.
8. Patients can be on the steroid treatment within 45 days before Ustekinumab
9. 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
10. 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:

1. Patients younger than 18 years of age
2. Patients with persistent gastrointestinal infection confirmed with positive testing despite completing 5 days of antibiotics
3. Patients with history of inflammatory bowel disease and/or radiation enterocolitis with active disease status at the time of study treatment initiation
4. Pregnant and breastfeeding women
5. 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
6. 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
7. 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

Where this trial is running

Houston, Texas

• The University of Texas M. D. Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Yinghong Wang, MD,PHD — M.D. Anderson Cancer Center
• Study coordinator: Yinghong Wang, MD,PHD

Conditions Cancer