Lowering steroid use for immune-related hepatitis

A Study to Evaluate the Efficacy and Safety of Steroid Sparing Strategy in Immune Related Hepatitis

This trial tests whether careful monitoring with steroids given only if needed works as well as starting high-dose steroids right away for people who develop hepatitis from immune checkpoint inhibitors.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AHS Cancer Control Alberta (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Calgary, Alberta)
• Trial ID: NCT05345847 on ClinicalTrials.gov

What this trial studies

This randomized phase II non-inferiority trial compares active surveillance with corticosteroid rescue to early high‑dose corticosteroids in patients who develop grade 2–3 immune-related hepatitis while on PD‑1/PD‑L1 (± CTLA‑4) therapy. Participants are enrolled within 10 days of hepatitis diagnosis and randomized to either close liver monitoring with steroids only if liver tests worsen or to immediate high‑dose steroid treatment. The study collects clinical and laboratory data, using RUCAM causality assessment, to identify predictors of spontaneous resolution versus need for immunosuppression. Findings will inform when steroids can be safely withheld and when prompt treatment is required.

Who should consider this trial

Good fit: Adults (≥18) with cancer on anti‑PD‑1 or anti‑PD‑L1 therapy (with or without anti‑CTLA‑4) who develop CTCAE v5.0 grade 2 or 3 immune‑related hepatitis, enroll within 10 days of diagnosis, have ECOG 0–2, and a RUCAM score ≥6.

Not a fit: Patients with grade 4 liver injury, alternative (non‑immune) causes of hepatitis, or who cannot comply with close follow‑up and monitoring are unlikely to benefit from the surveillance approach.

Why it matters

Potential benefit: If successful, the approach could spare many patients from prolonged high‑dose steroids and their side effects while maintaining liver safety.

How similar studies have performed: Small retrospective series and observational reports suggest some patients may recover without immediate high‑dose steroids, but randomized evidence is limited, so this approach remains relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Patients must be 18 years of age, or older on the day of signing informed consent.
2. Patients must be capable of providing consent to enrolment and treatment.
3. Patients with a performance status of ECOG 0-2 will be eligible for enrolment.
4. Patients with histologically confirmed cancer receiving anti-PD1 or anti-PDL1 monoclonal antibody ICI therapy, either alone or in combination with anti-CTLA-4 monoclonal antibody ICI therapy who develop CTCAEv5.0 grade 2 or grade 3 hepatitis that has developed on, or after, ICI therapy and is felt to be treatment related (irH). Patients must be enrolled on trial within 10 days of diagnosis of grade 2 or grade 3 hepatotoxicity.
5. Absence of any condition hampering compliance with the study protocol and follow- up schedule; those conditions should be discussed with the patient before registration in the trial.
6. Assessment by the Roussel Uclaf Causality Assessment Method (RUCAM) ≥6 showing probable relationship between ICI and liver injury (appendix)

Exclusion Criteria:

1. History underlying liver disease, including, but not limited to: hepatitis B, C, autoimmune hepatitis, primary biliary sclerosis, hemochromatosis, primary sclerosis cholangitis, portal vein thrombosis, Budd Chiari syndrome, alcohol induced hepatitis, suspected drug-induced liver injury from other cause (e.g. acetaminophen, antibiotics, statins, methyldopa, non-prescription herbs, see NIH LiverTox website https://livertox.nih.gov for comprehensive list).
2. If undertaken, liver biopsy supporting a cause of liver dysfunction other than irH
3. Patients with an indication for systemic immunosuppressive medications or corticosteroids. Patients with CTCAEv5.0 grade ≥2 irAE's other than irH (ie. colitis, pneumonitis, rash, etc.) are not eligible for trial, with the exception of endocrinopathies that are being treated with hormone replacement alone and not systemic immunosuppressive medications or corticosteroids.
4. Abnormal International Normalization Ratio (INR) at baseline (≥1.5) and bilirubin ≥60, ALT of ≥10X.
5. Previous use of targeted therapies for treatment of malignancy (e.g. BRAF, MEK, EGFR, and VEGF inhibitors) or current treatment with chemotherapy
6. Present use of warfarin.
7. Diagnosis of immunodeficiency.
8. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
9. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAEv5.0 Grade ≥ 3).
10. Other severe acute or chronic medical conditions including inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Where this trial is running

Calgary, Alberta

• Arthur J.E. Child Comprehensive Cancer Centre — Calgary, Alberta, Canada (Recruiting)

Study contacts

• Principal investigator: Omar Khan, MD — AHS Cancer Control Alberta
• Study coordinator: Omar F Khan, MD

Conditions Hepatitis Immune; immune related hepatitis; steroid sparing