Overview

Itacitinib for the Treatment Steroid Refractory Immune Related Adverse Events Arising From Immune Checkpoint Inhibitors

Status:
Not yet recruiting
Trial end date:
2026-03-01
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Douglas Johnson
Collaborator:
Incyte Corporation
Criteria
Inclusion Criteria:

- Must have signed and dated an IRB/IEC approved written informed consent form in
accordance with regulatory and institutional guidelines. This must be obtained before
the performance of any protocol related procedures that are not part of normal
participant care.

- Must be willing and able to comply with scheduled visits, treatment
schedule,laboratory tests, biopsies, and other requirements of the study.

- Must have received at least one immune checkpoint inhibitor (ICI) therapy either as
single agent(s) or in combination(s), including but not limited to nivolumab,
ipilimumab, pembrolizumab, cemiplimab, atezolizumab, durvalumab, or avelumab.

- Must experience at least one Grade 2, 3 or 4 (CTCAE Version 5.0)
toxicity/immune-related adverse event (irAE) attributed to immune checkpoint inhibitor
(ICI) therapy as diagnosed by the patient's study physician. This may be established
by clinical, histological, or imaging criteria as defined below:

- Symptoms must be attributed to an immune-related adverse event (irAE), with no
infectious or alternative cause suspected by the patient's study physician.

- Must be actively experiencing Grade 2+ irAE (at the time of screening) as broadly
defined below:

- Cutaneous toxicity (including skin rash)

- Colitis/enteritis (As defined by Grade 2+ diarrhea or Grade 2+ colitis
(either or both conditions)

- Pneumonitis

- Arthritis

- Hepatitis (As defined by Grade 2+ elevation in AST or ALT (either or both values
elevated)

- Nephritis (As defined by either Grade 2+ elevation in creatinine and/or
proteinuria of at least 2+ on urinalysis attributed to ICI)

- Myocarditis (Given the vague nature of symptomatic myocarditis grading, troponin
levels will be primarily used to grade myocarditis,( Troponin >2ng/ml), (Presumed
diagnosis of myocarditis (myocardial infarction ruled out clinically)

- Myositis (Defined as grade 2 myositis symptoms per CTCAE OR grade 2 elevations in
creatinine kinase levels)

- Neurologic toxicity

- Encephalitis

- Neurologic symptoms consistent with encephalitis

- Lumbar puncture and infectious disease consult to rule out infectious
etiologies if clinical suspicion for infectious causes

- Guillain Barre

- MRI performed to rule out spinal cord compression

- Neurology consult to confirm diagnosis (or extremely high suspicion)

- Myasthenia Gravis

- MRI performed to rule out spinal cord compression and brain metastases

- Neurology consult to confirm diagnosis (or extremely high suspicion)

- Pericarditis

- Vasculitis

- Gastritis

- Other toxicities

- Other steroid refractory toxicities not listed in the above list

- NOTE: Endocrine toxicities (including hypophysitis, hypopituitarism,
hypothyroidism, thyrotoxicosis, immune checkpoint inhibitor-induced
diabetes, and primary adrenal insufficiency) will NOT qualify for inclusion.

- Must have received oral or intravenous corticosteroids of at least 50mg per day
prednisone equivalent dosing (approximately 1mg/kg daily) for ≥ 48 hours of therapy
with worsening or lack of improvement to Grade 2.

- May have been treated with additional immunomodulators (one or more) prior to study
entry (e.g. infliximab, mycophenolate mofetil, intravenous immunoglobulin), provided
such immunomodulators are discontinued prior to first dose of study therapy.

- Adequate organ and marrow function as defined below:

- White blood cell (WBC) ≥ 2.0 ×109/L.

- Neutrophil (ANC) ≥ 1.5 ×109/L.

- Platelet (PLT) ≥ 75 ×109/L.

- Hemoglobin (Hgb) ≥ 8.0 g/dL.

- AST and ALT ≤ 3 x ULN in subjects without hepatic metastases; AST and ALT ≤ 5 x
ULN in subjects with hepatic metastases, if AST/ALTelevation is NOT due to
ICI-induced hepatitis; (Exception (without or with hepatic metastases): no limit
for patients with ICI-induced hepatitis).

- Total bilirubin ≤ 2 x ULN not due to ICI-hepatitis (except subjects with Gilbert
syndrome, where total bilirubin must be < 3.0 mg/dL), (Exception: no limit for
patients with ICI-induced hepatitis).

- Reproductive status:

- Women of childbearing potential must have a negative serum or urine pregnancy
test within 7 days prior to the start of study treatment.

- Women must not be breastfeeding.

- Women of childbearing potential must agree to follow instructions for method(s)
of contraception for the duration of study drug treatment and 60 days after the
last dose of study treatment or longer if required based on prior immunotherapy
received (for example, at least 4-5 months for nivolumab and pembrolizumab).

- Males who are sexually active with Women of childbearing potential must agree to
follow instructions for method(s) of contraception for the duration of study
treatment and 60 days after the last dose of study drug or longer if required
based on prior immunotherapy received.

- Azoospermic males are exempt from contraceptive requirements. WOCBP who are
continuously not heterosexually active are also exempt from contraceptive
requirements but still must undergo pregnancy testing as described in this
section.

- Investigators shall counsel Women of childbearing potential, and male
participants who are sexually active with Women of childbearing potential on the
importance of pregnancy prevention and the implications of an unexpected
pregnancy. Investigators shall advise on the use of highly effective methods of
contraception which have a failure rate of < 1% when used consistently and
correctly. Women of childbearing potential and men must agree to use adequate
contraception (for example, hormonal or barrier method of birth control;
abstinence) prior to study entry and for the duration of protocol treatment.

Exclusion Criteria:

- Toxicity deemed by patient's study physician to be primarily caused by another
etiology (bacterial infection, other anticancer agents, etc.).

- Ongoing serious infection requiring IV antibiotics.

- Prior treatment with a JAK inhibitor within the past 8 weeks before first dose of
protocol indicated treatment.

- Known HIV infection with CD4 count < 200. (Testing not required by this study.)

- History or current diagnosis of cardiac disease indicating significant risk of safety
for participation in the study, such as uncontrolled or significant cardiac disease,
including any of the following:

- Recent myocardial infarction (within 6 months before first dose of protocol
indicated treatment).

- New York Heart Association Class III or IV congestive heart failure.

- Unstable angina (within last 6 months before first dose of protocol-indicated
treatment).

- Clinically significant (symptomatic) cardiac arrhythmias per judgment of
patient's study physician (e.g., sustained ventricular tachycardia, and
clinically significant second or third degree AV block without a pacemaker).

- Uncontrolled hypertension defined as blood pressure persistently above 160
systolic or 100 diastolic despite antihypertensive therapy.

- Known allergies, hypersensitivity, or intolerance to any study medications or
excipients.

- History of solid organ transplant or allogeneic stem cell transplant with active graft
versus host disease.

- Any condition that would, in the investigator's judgment, interfere with full
participation in the study, including administration of study drug/treatment and
attending required study visits; pose a significant risk to the participant; or
interfere with interpretation of study data