This phase II trial tests how well itacitinib works in in patients with immune related adverse events (irAEs) arising from immune checkpoint inhibitors (ICI) that do not respond to steroids (steroid refractory). Steroids are the usual treatment for these side effects. However, sometimes steroids do not improve or fix the side effects. Giving itacitinib may be effective in treating patients with known or suspected problems coming from ICIs, that do not resolve or improve with steroids, by reducing the patients immune system response that can cause the irAEs.
PRIMARY OBJECTIVE: I. To define the rate of improvement of steroid-refractory immune related adverse events (irAEs) in patients treated with ICI at 28 days. SECONDARY OBJECTIVES: I. To define whether anti-tumor activity is preserved (response rate, progression free survival \[PFS\], T cell populations and function in the tumor). II. To assess freedom from hospitalization and any grade improvement at 14 and 28 days. III. To assess rate of therapy escalation (increased dose of steroids, other immunosuppressant) by day 60 follow up. IV. To define cancer-specific and toxicity-specific survival at 6 months. V. To define the rate of improvement of steroid-refractory irAEs in patients treated with ICI at any time, and at 60 days (defined as improvement to Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 0-1). VI. To define the proportion of patients able to be tapered off steroids at Day 29 and at Day 30 follow up. VII. To define the safety of itacitinib in patients with steroid-refractory irAEs. OUTLINE: Patients receive itacitinib orally (PO) and corticosteroids PO or intravenously (IV) on study. Patients may undergo endoscopy and skin biopsy throughout the study. Patients also undergo blood collection throughout the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given by mouth
Given by mouth or by vein
Undergo endoscopic procedure
Incidence of immune related adverse events (irAE)
Time frame: Baseline up to 60 days post last dose of itacitinib
Objective response rate
Will be measured by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as best response reported by the investigator at scans subsequent to itacitinib therapy and will be obtained descriptively by chart review.
Time frame: Baseline up to 60 days post last dose of itacitinib
Progression-free survival
Will be obtained using RECIST 1.1 and obtained descriptively by chart review.
Time frame: Baseline up to 60 days post last dose of itacitinib
Hospitalization presence
Need for hospitalization will be recorded.
Time frame: Days 14 and 28
Need for therapy escalation and presence of steroids
The presence of additional immunosuppression added after starting itacitinib or escalation of steroid dose will be recorded.
Time frame: From start of itacitinib to 60 days after stopping itacitinib
Need for therapy escalation and absence of steroids
The absence of additional immunosuppression added after starting itacitinib or escalation of steroid dose will be recorded.
Time frame: From start of itacitinib to 60 days after stopping itacitinib
The rate of delayed relapses will be followed.
Rate of irAEs
Time frame: Baseline up to 60 days post last dose of itacitinib
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Undergo skin biopsy
Undergo collection of blood and stool
The rate of improvement at earlier timepoints will be followed.
Rate of irAEs
Time frame: Baseline up to 60 days post last dose of itacitinib
Rate of irAEs
The rate of ability to resume ICI (in select patients, per study investigator decision) will be followed.
Time frame: Baseline up to 60 days post last dose of itacitinib