Immune-mediated HepatitisPhase 2NCT07663422
Mycophenolate Mofetil w/ Prednisone for Immune Related Hepatitis From Checkpoint Inhibitor Therapy
A Phase 2 study testing Mycophenolate Mofetil plus prednisone in people with Immune-mediated Hepatitis and Immune-related Adverse Event, run by Fox Chase Cancer Center at 1 site in United States.
Trial summary
This phase II study evaluates whether early treatment with mycophenolate mofetil (MMF) plus prednisone improves liver inflammation caused by immune checkpoint inhibitors. The study includes patients who develop moderate to severe immune-related hepatitis after receiving PD-(L)1 or CTLA-4-based cancer therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immune-mediated Hepatitis, Immune-related Adverse Event
- What is being tested?
- Mycophenolate Mofetil plus prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Jul 2026to 30 Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must be ≥ 18 years at the time of irAE diagnosis and must have been diagnosed with a solid tumor or hematologic malignancy being treated with non-curative intent.
- Patients must be diagnosed or presumed to have by a treating Medical Oncology or Hematology-Oncology clinician with immune-related hepatitis, G2-G3 (as defined in section 11.0), with plan for at least temporary interruption of IO therapy and initiation of corticosteroid treatment.
- Patients must have been previously treated for any malignancy with at least one dose of an IO agent targeting the Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PDL-1) or CTLA-4 axis. IO use may have occurred at any time prior to diagnosis of irAE.
- Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin must have been measured within screening window outlined in Section 8.0 (Study Calendar).
- Patient must be able to take study medications by mouth.
- Baseline hemoglobin (HgB) at time of enrollment ≥8.0 g/dL, absolute neutrophil count (ANC) ≥ 1500/mm3, and platelet count ≥ 100,000/mm3 without red blood cell or platelet transfusion in the two weeks preceding measurement of lab values. Lab values are to be assessed within screening window outlined in Section 8.0 (Study Calendar).
- Baseline estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73m2
- Patients must be able to understand and willing to sign a written informed consent and HIPAA consent document.
Who cannot join
- Patients previously treated for irAE hepatitis.
- Patients diagnosed or presumed to have G4 immune-related hepatitis.
- Patients receiving renal replacement therapy with hemodialysis or peritoneal dialysis at time of enrollment.
- Patients with a documented history of Child-Turcotte-Pugh class B and C liver dysfunction.
- Patients with significant liver dysfunction at time of presentation, as defined by an otherwise unexplained change in mental status or International Normalized Ratio (INR) ≥ 1.5 attributed to synthetic liver dysfunction.
- Patients with active hepatitis B (HBV), hepatitis C (HCV), or tuberculosis. Confirmatory testing for these infections may be performed if no recent result is available in the patient's records and, in the opinion of the treating physician, such testing is clinically warranted. Past HBV is exclusionary. Patients with treated HCV infection and documented eradication are eligible to enroll.
Show all 23Show fewer
- Patients with uncontrolled human immunodeficiency virus (HIV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), or Varicella-zoster virus (VZV). Confirmatory testing for these infections is not required.
- Patients with a history of gastrointestinal bleeding, ulceration, or perforations within one year of trial enrollment. Use of proton-pump inhibitor therapy is allowed.
- Patients with any history of solid organ or allogeneic stem cell transplantation.
- Patients with type I diabetes mellitus (DM).
- Patients with type II DM with most recent glycated hemoglobin measurement greater than or equal to 9.0%.
- Patients with a documented history of phosphoribosyl-transferase deficiency.
- History of allergic reactions to MMF, prednisone, methylprednisolone, or dexamethasone.
- Patients with decompensated congestive heart failure at time of enrollment, at the discretion of treating clinician, regardless of ejection fraction.
- Patients with history of suicidal ideation or past suicide attempt.
- Uncontrolled or intercurrent severe medical illness at the time of enrollment, as defined below:
- Patients being treated with vasopressors
- Patient requiring mechanical ventilation or extracorporeal membrane oxygenation
- Patients being treated with parenteral antibiotic, antifungal, or antiviral medications
- Patients with chronic autoimmune diseases requiring long-term immunosuppressive treatment at the time of enrollment, or for whom the mechanism of index inflammatory changes is too uncertain to initiate irAE-directed treatment at the discretion of treating provider.
- Patients with congenital (e.g. combine variable immunodeficiency) or acquired (e.g. chronic leukemia) immunodeficiency requiring long-term prophylactic antimicrobial treatment at time of enrollment (e.g. intravenous immunoglobulin (IVIg), prophylactic antiviral treatment, etc.)
- Women of child-bearing potential (WOCBP) who are pregnant or breast-feeding.
- Patients unable to commit to use of reliable contraception throughout the study period.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Ryan Romasko, 215-214-1515, ProtocolDev@fccc.edu
About this study
Official title: GU-228: Mycophenolate Mofetil in Combination With Prednisone as First-line Treatment of Immune Related Hepatitis Resulting From Checkpoint Inhibitor Therapy
This phase II study evaluates whether early treatment with mycophenolate mofetil (MMF) plus prednisone improves liver inflammation caused by immune checkpoint inhibitors. The study includes patients who develop moderate to severe immune-related hepatitis after receiving PD-(L)1 or CTLA-4-based cancer therapy. The main goal is to determine how many patients experience improvement in liver function within 30 days while successfully tapering steroids. Safety and treatment-related side effects will also be monitored.
Read the detailed description
This is a phase II, interventional clinical trial evaluating the efficacy and safety of combination immunosuppression with mycophenolate mofetil (MMF) plus prednisone for the treatment of grade 2-3 immune-related adverse event (irAE) hepatitis associated with immune checkpoint inhibitor therapy (PD-(L)1 and/or Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors).
Eligible patients are those with laboratory-defined grade 2-3 hepatitis and a clinical diagnosis consistent with irAE hepatitis. When feasible, liver biopsy is obtained within 120 hours of diagnosis to confirm the diagnosis and evaluate alternative causes of liver injury; however, biopsy is not required in patients where the procedure is deemed unsafe (e.g., due to coagulopathy or ascites). Treatment initiation must occur within 72 hours of diagnosis. In select patients where clinically appropriate, immunosuppressive therapy may be delayed up to 48 hours to allow for diagnostic evaluation, including biopsy and viral testing.
Patients in whom an alternative cause of liver injury is considered more likely (e.g., tumor involvement) or whose liver function improves to grade 1 or lower without intervention will not receive protocol-directed treatment and will instead enter an observational follow-up cohort. Patients with grade 4 hepatitis at presentation are excluded due to safety concerns with the study's treatment approach.
All treated patients receive combination therapy consisting of fixed-dose MMF and physician-directed prednisone. Prednisone tapering is guided by suggested protocols but ultimately determined by the treating physician. Dose modification guidelines are provided for MMF.
The primary endpoint is treatment response at 30 days from irAE hepatitis diagnosis, defined as improvement to grade 0-1 hepatitis with successful steroid taper to ≤20 mg prednisone equivalent daily. The primary analysis will be conducted on an intention-to-treat basis.
The study uses a Simon two-stage design to evaluate efficacy. The null hypothesis assumes a response rate of ≤60%, while the alternative hypothesis assumes a response rate of ≥80%. Stage I includes 11 evaluable patients, and Stage II includes 20 patients, with interim futility analyses conducted at each stage. Early safety monitoring includes toxicity assessment in the first 8 patients. A steering committee will regularly review safety data to monitor for patient harm.
Treatment failure is defined as lack of response at 30 days or death attributable to irAE, severe infection, or treatment-related toxicity. Death due to underlying cancer progression is not considered treatment failure.
This study aims to determine whether early combination immunosuppression can improve outcomes in patients with immune-mediated hepatitis while maintaining an acceptable safety profile.
- Being tested
- Mycophenolate Mofetil plus prednisone
- Keywords
- irAE, Immune-mediated hepatitis, Immune-related Adverse Event
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mycophenolate Mofetil plus prednisoneDrug
MMF dosing is 1000 mg orally twice daily, and dosing for individual patients will be managed based on toxicity monitoring rules. The addition of alternative agents for treatment of irAEs will be at the treating Oncologist/Hematologist's discretion. Patients for whom prednisone is held may resume those agents at treating Oncologist/Hematologist's discretion, while rules for MMF re-challenge are stipulated. At the end of the 30-day primary study period, patients may continue one or both agents as deemed appropriate by the treating physician.
| Study group | Role | What they receive |
|---|---|---|
| Mycophenolate mofetil (MMF) and prednisone | Experimental | Patients who present with G2-3 irAE hepatitis by lab value and confirmed diagnosis by liver biopsy will be treated with combination therapy of MMF plus prednisone for 30 days Receives: Drug: Mycophenolate Mofetil plus prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate of immunotherapy (IO)-related hepatitis to MMF and prednisone
The response rate of IO-related hepatitis to MMF and prednisone defined as achievement of corticosteroid (CS) dose of ≤ 20 mg prednisone with improvement to G1 or better as protocol defined at day 30 following treatment initiation
Measured: 30 days
Secondary outcomes (1)
Frequency of bacterial, viral, or fungal infection requiring systemic treatment
The frequency of bacterial, viral, or fungal infection requiring systemic treatment within 90 days of initiation of MMF plus prednisone
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2026
- Study start23 Jul 2026
- Primary completion31 Mar 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immune-mediated HepatitisStudies of the same condition, open and under way.
- More trials run by Fox Chase Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fox Chase Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthew Zibelman, MD, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07663422
- Sponsor's protocol ID
- 25-1048
- Other IDs
- GU-228
- Status last verified
- Sep 2026
- First submitted
- 17 Jun 2026
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GU-228: Mycophenolate Mofetil in Combination With Prednisone as First-line Treatment of Immune Related Hepatitis Resulting From Checkpoint Inhibitor Therapy
- ClinicalTrials.gov ID
- NCT07663422
- Acronym / sponsor ID
- 25-1048
- Keywords
- irAE, Immune-mediated hepatitis, Immune-related Adverse Event
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- Fox Chase Cancer CenterUniversity, hospital or other
- Study start
- 23 Jul 2026 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 23 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II study evaluates whether early treatment with mycophenolate mofetil (MMF) plus prednisone improves liver inflammation caused by immune checkpoint inhibitors. The study includes patients who develop moderate to severe immune-related hepatitis after receiving PD-(L)1 or CTLA-4-based cancer therapy. The main goal is to determine how many patients experience improvement in liver function within 30 days while successfully tapering steroids. Safety and treatment-related side effects will also be monitored.
Detailed description
This is a phase II, interventional clinical trial evaluating the efficacy and safety of combination immunosuppression with mycophenolate mofetil (MMF) plus prednisone for the treatment of grade 2-3 immune-related adverse event (irAE) hepatitis associated with immune checkpoint inhibitor therapy (PD-(L)1 and/or Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) inhibitors).
Eligible patients are those with laboratory-defined grade 2-3 hepatitis and a clinical diagnosis consistent with irAE hepatitis. When feasible, liver biopsy is obtained within 120 hours of diagnosis to confirm the diagnosis and evaluate alternative causes of liver injury; however, biopsy is not required in patients where the procedure is deemed unsafe (e.g., due to coagulopathy or ascites). Treatment initiation must occur within 72 hours of diagnosis. In select patients where clinically appropriate, immunosuppressive therapy may be delayed up to 48 hours to allow for diagnostic evaluation, including biopsy and viral testing.
Patients in whom an alternative cause of liver injury is considered more likely (e.g., tumor involvement) or whose liver function improves to grade 1 or lower without intervention will not receive protocol-directed treatment and will instead enter an observational follow-up cohort. Patients with grade 4 hepatitis at presentation are excluded due to safety concerns with the study's treatment approach.
All treated patients receive combination therapy consisting of fixed-dose MMF and physician-directed prednisone. Prednisone tapering is guided by suggested protocols but ultimately determined by the treating physician. Dose modification guidelines are provided for MMF.
The primary endpoint is treatment response at 30 days from irAE hepatitis diagnosis, defined as improvement to grade 0-1 hepatitis with successful steroid taper to ≤20 mg prednisone equivalent daily. The primary analysis will be conducted on an intention-to-treat basis.
The study uses a Simon two-stage design to evaluate efficacy. The null hypothesis assumes a response rate of ≤60%, while the alternative hypothesis assumes a response rate of ≥80%. Stage I includes 11 evaluable patients, and Stage II includes 20 patients, with interim futility analyses conducted at each stage. Early safety monitoring includes toxicity assessment in the first 8 patients. A steering committee will regularly review safety data to monitor for patient harm.
Treatment failure is defined as lack of response at 30 days or death attributable to irAE, severe infection, or treatment-related toxicity. Death due to underlying cancer progression is not considered treatment failure.
This study aims to determine whether early combination immunosuppression can improve outcomes in patients with immune-mediated hepatitis while maintaining an acceptable safety profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mycophenolate mofetil (MMF) and prednisone | Experimental | Drug: Mycophenolate Mofetil plus prednisonePatients who present with G2-3 irAE hepatitis by lab value and confirmed diagnosis by liver biopsy will be treated with combination therapy of MMF plus prednisone for 30 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must be ≥ 18 years at the time of irAE diagnosis and must have been diagnosed with a solid tumor or hematologic malignancy being treated with non-curative intent.
- Patients must be diagnosed or presumed to have by a treating Medical Oncology or Hematology-Oncology clinician with immune-related hepatitis, G2-G3 (as defined in section 11.0), with plan for at least temporary interruption of IO therapy and initiation of corticosteroid treatment.
- Patients must have been previously treated for any malignancy with at least one dose of an IO agent targeting the Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PDL-1) or CTLA-4 axis. IO use may have occurred at any time prior to diagnosis of irAE.
- Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin must have been measured within screening window outlined in Section 8.0 (Study Calendar).
- Patient must be able to take study medications by mouth.
Key exclusion criteria (23 listed)
- Patients previously treated for irAE hepatitis.
- Patients diagnosed or presumed to have G4 immune-related hepatitis.
- Patients receiving renal replacement therapy with hemodialysis or peritoneal dialysis at time of enrollment.
- Patients with a documented history of Child-Turcotte-Pugh class B and C liver dysfunction.
- Patients with significant liver dysfunction at time of presentation, as defined by an otherwise unexplained change in mental status or International Normalized Ratio (INR) ≥ 1.5 attributed to synthetic liver dysfunction.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mycophenolate Mofetil plus prednisoneMMF dosing is 1000 mg orally twice daily, and dosing for individual patients will be managed based on toxicity monitoring rules. The addition of alternative agents for treatment of irAEs will be at the treating Oncologist/Hematologist's discretion. Patients for whom prednisone is held may resume those agents at treating Oncologist/Hematologist's discretion, while rules for MMF re-challenge are stipulated. At the end of the 30-day primary study period, patients may continue one or both agents as deemed appropriate by the treating physician. | Drug | Mycophenolate mofetil (MMF) and prednisone |
Primary outcome
Response rate of immunotherapy (IO)-related hepatitis to MMF and prednisone
Time frame: 30 days
The response rate of IO-related hepatitis to MMF and prednisone defined as achievement of corticosteroid (CS) dose of ≤ 20 mg prednisone with improvement to G1 or better as protocol defined at day 30 following treatment initiation
1 secondary outcome
Frequency of bacterial, viral, or fungal infection requiring systemic treatment
Time frame: 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2026.
- Individual participant dataSharing planned: No
Related trials for Immune-mediated Hepatitis
RecruitingPhase 2
Comparing UDCA and Corticosteroids in Immunotherapy Induced Cholestatic Hepatitis
Immune-Mediated Cholestasis
RecruitingObservational study
Checkpoint Inhibitor-induced Liver Injury
Immune-Mediated Hepatitis
RecruitingObservational study
Specific Biomarkers of Immune-mediated Hepatitis Secondary to Immune Checkpoint Inhibitors
Immune-mediated Hepatitis
RecruitingObservational study
Management of Immune Checkpoint Inhibition-related Hepatitis Using Low-dose Corticosteroids
Immune Related Adverse Events, Immune-Mediated Hepatitis
Recruiting
Efficacy and Safety of ALSS Treatment for ICIs-LF in Patients With HCC
Immune-Mediated Hepatitis, Liver Failure
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Matthew Zibelman, MD principal investigator
Fox Chase Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mycophenolate Mofetil plus prednisone in people with Immune-mediated Hepatitis and Immune-related Adverse Event, run by Fox Chase Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ryan Romasko (2678388380, ProtocolDev@fccc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response rate of immunotherapy (IO)-related hepatitis to MMF and prednisone (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2026.