Etrasimod for Immune Checkpoint Inhibitor Diarrhea and Colitis

NCT06521762 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 2000036896
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

Immune Checkpoint Inhibitor-Related Diarrhea and Colitis

Outcome Measures

Primary Outcomes (1)

• Average daily weight-adjusted dose of corticosteroids use

  Average daily weight-adjusted dose of corticosteroids use (up to day 120 or when a censoring event occurs), accounting for both the weight-adjusted cumulative dose of steroids and the length of treatment.

  up to day 120 or when a censoring event occurs

Secondary Outcomes (6)

• Requirement for secondary immunosuppression

  up to day 120 or when a censoring event occurs

• Mean time to improvement

  up to day 120 or when a censoring event occurs

• Mean number of days without corticosteroids use

  up to day 120 or when a censoring event occurs

• Safety and Tolerability Measured by Assessing Incidence and severity of adverse events of special interest.

  up to day 120 or when a censoring event occurs

• Incidence and severity of laboratory abnormalities

  up to day 120 or when a censoring event occurs

Study Arms (2)

Etrasimod plus corticosteroids

EXPERIMENTAL

Participants will receive Etrasimod plus corticosteroids, to be given up to 120 days, to treat IMDC.

Drug: Etrasimod; Drug: Corticosteroids

Placebo plus corticosteroids

PLACEBO COMPARATOR

Participants will receive Placebo plus corticosteroids, to be given up to 120 days, to treat IMDC.

Drug: Placebo; Drug: Corticosteroids

Interventions

Etrasimod DRUG

2 mg/day oral tablet

Also known as: VELSIPITY

Etrasimod plus corticosteroids

Placebo DRUG

matching placebo oral tablet

Placebo plus corticosteroids

Corticosteroids DRUG

Corticosteroids will be given in conjunction with study drug or placebo

Etrasimod plus corticosteroids; Placebo plus corticosteroids

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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:
• difficile infection, or an intestinal bacterial or parasitic infection detected by a multiplexed stool infection assay
• Have received treatment for C. difficile infection within 30 days or another intestinal pathogen within 30 days prior to enrollment
• Have a known history of active or latent tuberculosis, or active hepatitis B or hepatitis C
• 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
• Have evidence of abdominal abscess or toxic megacolon at the initial screening visit
• Patients with diabetes mellitus that meet the following criteria:
• Type 1 diabetes mellitus
• 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:
• 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.
• Unstable ischemic heart disease, Class I or II heart failure, history of cardiac arrest, cerebrovascular disease, or uncontrolled hypertension, unless consulting cardiologist believes safe

Sponsors & Collaborators

• Yale University: lead
• Pfizer: collaborator

Study Sites (1)

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Colitis

Interventions

etrasimod; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Harriet Kluger, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Harvey and Kate Cushing Professor of Medicine (Oncology) and of Dermatology

Study Record Dates

• First Submitted: July 21, 2024
• First Posted: July 26, 2024
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029
• Last Updated: January 14, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)