Early Vedolizumab as First-Line for Immune-Related Colitis Therapy Trial

Inclusion Criteria: * In order to participate in the study, a patient must meet all the following inclusion criteria: * Age ≥18 years. * Treatment with an ICI for cancer within the past 8 weeks. * Confirmed endoscopic/histologic diagnosis of ICI colitis. * Grade 2-3 diarrhea by Common Terminology Criteria for Adverse Events. * Willing and able to comply with the requirements of the protocol. * Ability to understand and the willingness to sign a written informed consent document. * Exclusion Criteria * Prior history of inflammatory colitis requiring treatment with greater than prednisone 10 mg daily or equivalent or any immunosuppressive medication. * Current or recent use of immunosuppressive biologic medication (for any reason including ICI colitis) within 4 weeks. * Concurrent immune-related adverse event requiring systemic steroids or systemic immunosuppression within 2 weeks. * Colonic perforation or abscess. * Partial or complete bowel obstruction within the last 3 months, signs/symptoms of bowel obstruction, or known radiologic evidence of impending obstruction. * Active Clostridium difficile or other colonic infection. * Concurrent hepatitis B or C infection. * History of untreated tuberculosis and/or positive quantiferon/Tspot test without previous tuberculosis prophylaxis, or untreated active infection with mycobacterium tuberculosis. * Active or known prior infection with nontuberculous mycobacteria (NTM). * Unable or unwilling to undergo a colonoscopy/flexible sigmoidoscopy. * Inpatient status, though patients can be screened while inpatients, they must be outpatient for the planned treatment of ICI colitis. * History of total proctocolectomy. * Female patients who are pregnant or breastfeeding or plan to become pregnant in the next 6 months. * Patients who are unable to give informed consent. * Previous SARS-CoV-2 infection within 10 days for mild infections or 20 days for severe/critical illness prior to first Vedolizumab dose. * Unable to adhere to protocol requirements. * Any condition that the physician investigators deem unsafe, including other conditions or medications that the investigator determines will put the subject at greater risk from vedolizumab plus brief course of steroids. * Allergy to sulfamethoxazole-trimethoprim. * Weight greater than 120 kg.