Etrasimod for Immune Checkpoint Inhibitor Diarrhea and Colitis

Eligibility 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)
• * 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