Etrasimod for Immune Checkpoint Inhibitor Diarrhea and Colitis
This is a randomized, double-blind, placebo-controlled, two-arm phase 2 study of etrasimod plus corticosteroids versus placebo plus corticosteroids for the treatment of IMDC CTCAE v5.0 grade ≥ 2 due to ICI therapy alone (α-PD-(L)1 monotherapy or combined with another ICI, such as α-CTLA-4 or α-LAG-3) or ICI plus an oral tyrosine kinase inhibitor that in the opinion of the treating physician requires treatment with corticosteroid-based immunosuppression and does not require immediate secondary immune suppression, such as vedolizumab or infliximab (or equivalent). IMDC is one of the most common Immune Related Adverse Events (irAEs) from treatment with ICI. Current guidelines recommend steroid treatment for IMDC CTCAE grade ≥ 2, which requires temporary or permanent cessation of ICI therapy. Corticosteroids may interfere with the anti-tumor activity of ICIs and are therefore not co-administered. Strategies are needed to both reduce the dose and duration of corticosteroids needed for IMDC treatment and minimize the duration off ICI therapy before re-administering ICI (for those patients in whom it is deemed safe to rechallenge).
• 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:
‣ No known history of inflammatory bowel disease
⁃ Vital signs at screening: pulse rate ≥ 50 beats per minute, systolic blood pressure ≥ 90 mm Hg, and diastolic blood pressure ≥ 55 mm Hg
⁃ 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:
‣ Non-pregnant, as determined by qualitative urine hCG testing
⁃ Non-lactating
⁃ 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)