Etrasimod for Immune Checkpoint Inhibitor Diarrhea and Colitis

Inclusion Criteria: * Locally advanced unresectable or metastatic cancer * Any tumor type being treated with either α-PD-(L)1 monotherapy or combination therapy containing α-PD-(L)1 and another ICI such as α-CTLA-4 or α-LAG-3 therapy. * Patients receiving ICI(s) in combination with oral tyrosine kinase inhibitors (TKIs) may be enrolled if their diarrhea persists despite holding the TKI for 5 days and they meet the other eligibility criteria. These cases should be discussed with one of the study PIs. Patients receiving chemotherapy in combination with ICI(s) cannot be enrolled. * Grade ≥ 2 IMDC requiring immunosuppression with corticosteroids as defined by at least grade 2 diarrhea and grade 2 colitis by CTCAE v5.0, which are defined in Appendix 3 (section 11.3) of the protocol. * Positive stool calprotectin test * Able to provide informed consent. * Able and willing to take the study medication and comply with all study requirements. * The following medical criteria are met: 1. No known history of inflammatory bowel disease 2. Vital signs at screening: pulse rate ≥ 50 beats per minute, systolic blood pressure ≥ 90 mm Hg, and diastolic blood pressure ≥ 55 mm Hg 3. 12-lead electrocardiogram (ECG) that showed no clinically significant abnormalities as defined by the clinician's judgement at the time the ECG was performed * Healthcare professional-confirmed history of varicella or a full course of vaccination against varicella zoster virus (VZV) or a positive antibody test to VZV * Eligible patients that were biologically female at birth must be: 1. Non-pregnant, as determined by qualitative urine hCG testing 2. Non-lactating 3. If premenopausal, be either surgically infertile OR using 2 acceptable methods of birth control for 30 days after the last dose of etrasimod is administered (inquire for a list of birth control methods considered acceptable) Exclusion Criteria * Patients receiving ICIs in the adjuvant setting. * Patients with severe hepatic impairment, as indicated by having a Child-Pugh C score. * The following infectious complications: 1. difficile infection, or an intestinal bacterial or parasitic infection detected by a multiplexed stool infection assay 2. Have received treatment for C. difficile infection within 30 days or another intestinal pathogen within 30 days prior to enrollment 3. Have a known history of active or latent tuberculosis, or active hepatitis B or hepatitis C 4. Have a known history of congenital or acquired immunodeficiency, including but not limited to common variable immune deficiency (CVID) and human immunodeficiency virus (HIV) infection 5. Have evidence of abdominal abscess or toxic megacolon at the initial screening visit * Patients with diabetes mellitus that meet the following criteria: 1. Type 1 diabetes mellitus 2. Uncontrolled type 2 diabetes mellitus requiring insulin for routine management * Have a history of severe respiratory disease (i.e., pulmonary fibrosis, asthma, and chronic obstructive pulmonary disease) requiring supplemental oxygen not related to an underlying malignancy * Have the following cardiovascular history: 1. In the last 6 months, experienced myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure. 2. Unstable ischemic heart disease, Class I or II heart failure, history of cardiac arrest, cerebrovascular disease, or uncontrolled hypertension, unless consulting cardiologist believes safe 3. History or presence of Mobitz type I or II second-degree, or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker. 4. A history or presence of recurrent symptomatic bradycardia or recurrent cardiogenic syncope, or severe untreated sleep apnea 5. QTcF interval ≥ 450 ms in men or ≥ 470 ms in women 6. Arrhythmias requiring treatment with Class Ia or Class III anti-arrhythmic drugs or QT prolonging drugs, unless consulting cardiologist believes safe * Have received treatment that could be considered secondary IMDC treatment within 4 half-lives of the agent, including but not limited to vedolizumab, anti-TNFα antibodies, and mycophenolate mofetil. Treatments that could be considered secondary IMDC treatment but are not specified in this protocol will be adjudicated by a study PI or co-PI at the time of screening. * Have a known history of macular edema * Have a history of any clinically significant medical condition that, in the investigator's opinion, precludes participation in the study * History of an opportunistic infection (e.g., Pneumocystis jirovecii, cryptococcal meningitis, progressive multifocal leukoencephalopathy) or history of disseminated herpes simplex or disseminated herpes zoster. * Have an absolute neutrophil count (ANC) or absolute lymphocyte count (ALC) \< 500 * Have received any investigational therapy, excluded medications (Appendix 4, section 11.4), or any approved therapy in an investigational protocol within 14 days before screening. * Have active psychiatric problems that, in the investigator's opinion, could interfere with compliance with the study procedures. * Have been using moderate to strong inhibitors of cytochrome P450 (CYP)2C9. * Unable to discontinue any of the drugs listed in Appendix 4 (section 11.4) of the protocol