Etrasimod for Immune Checkpoint Inhibitor Diarrhea and Colitis
brief summary
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).
detailed description
Participants will be screened as soon as IMDC is suspected but will not be randomized and administered the first dose of etrasimod or placebo until results from Clostridium difficile (C. difficile) and other intestinal infection assays are confirmed to be negative and stool calprotectin confirmed to be positive. If intestinal infectious studies are positive the participant will be excluded from the study. Due to the acute nature of some cases of IMDC (e.g., grade 4 IMDC), some participants may require initiation of corticosteroids before enrollment. In these cases, participants may be enrolled if the first dose of etrasimod or placebo can be administered within 96 hours of the first dose of corticosteroids. Participants will undergo flexible sigmoidoscopy or colonoscopy with colon biopsy prior to, within the first 7 days of starting study drug, which will be repeated 7 to 14 days after completing the last dose of study drug.