Hepatocellular CarcinomaPhase 2NCT05027425
Durvalumab (MEDI4736) and Tremelimumab for Hepatocellular Carcinoma in Patients Listed for a Liver Transplant
A Phase 2 study testing Durvalumab, Tremelimumab and Liver Transplant in people with Hepatocellular Carcinoma and Cirrhosis, run by University of Cincinnati at 3 sites in United States.
Trial summary
Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma, Cirrhosis, Portal Hypertension
- What is being tested?
- Durvalumab, Tremelimumab and Liver Transplant
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 3 sitesUnited States
- Study dates
- 7 Dec 2021to 7 Nov 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Hepatocellular carcinoma, diagnosed either by biopsy or by combination of cirrhosis and imaging criteria (contrast-enhanced CT or MRI).
- Tumor confined to liver with no vascular invasion and no evidence of extrahepatic disease.
- Patient evaluated by institutional Liver Transplant team and listed for transplant.
- At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization.
- No prior therapy for HCC at any time.
- Age ≥18 years at the time of study entry.
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- ECOG score of 0 or 1
- Child-Pugh Score of 5, 6, or 7
- Body weight >30 kg
- Patients must have adequate organ and marrow function as defined in protocol
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Who cannot join
- Extrahepatic disease.
- Variceal bleeding during 3 months prior to registration.
- Any autoimmune disease deemed a risk in the setting of immunotherapy per treating physician's judgment.
- Any other illness or patient condition deemed a medical or logistical barrier for protocol therapy per treating physician's judgment.
- Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- Participation in another clinical study with an investigational product during the last 12 months Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
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- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
- History of allogenic organ transplantation.
- History of another primary malignancy except for:
- Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- Patients with celiac disease controlled by diet alone
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
- History of leptomeningeal carcinomatosis
- History of active primary immunodeficiency
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine while receiving IP and up to 30 days after the last dose of IP.
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 180 days after the last dose of durvalumab + tremelimumab combination therapy.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
- Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
- Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Cincinnati
Cincinnati, Ohio, 45267
Simmons Comprehensive Cancer Center UT Southwestern Medical Center
Dallas, Texas, 75235
Washington University School of Medicine
St Louis, Missouri, 63130
About this study
Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver transplant.
Read the detailed description
ESR-20-21010 is a single-arm, open-label, Phase II, multicenter clinical trial designed to evaluate the safety and efficacy of durvalumab and tremelimumab for the treatment of hepatocellular carcinoma (HCC) patients who have cirrhosis or portal hypertension and are evaluated by institutional Liver Transplant team and deemed eligible for transplant.
The key eligibility requirements include HCC, Child-Pugh score of up to 7, and ECOG PS of 0 or 1.
Patients will be treated with the immunotherapy combination for up to 4 months. After a minimum 28 day washout, they will undergo locoregional therapy per institutional standards. Eventually, after a minimum 72-day washout from the end of immunotherapy, they will undergo liver transplant.
The primary endpoint is proportion of patients experiencing post-transplant rejection (within 30 days of transplant). A total of 30 patients are to be enrolled, to allow at least 20 transplants for adequate primary endpoint analysis. An interim analysis after 10 patients will be performed to ensure safety. If there are untoward safety signals, study modification/discontinuation will be discussed.
- Conditions
- Hepatocellular Carcinoma, Cirrhosis, Portal Hypertension
- Being tested
- Durvalumab, Tremelimumab, Liver Transplant
- Keywords
- Transplant
- Medical subject headings
- Carcinoma, Hepatocellular, Fibrosis, Hypertension, Portal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736
1500 mg IV, Q4W
TremelimumabDrug
300 mg IV, 1 dose on day 1 of only the first cycle
Liver TransplantProcedure or surgery
minimum 72-day washout from the end of immunotherapy, patients will undergo liver transplant.
| Study group | Role | What they receive |
|---|---|---|
| Durvalumab + Tremelimumab + Liver Transplant | Experimental | Patients will be treated with the immunotherapy combination for up to 4 months. After a minimum 28 day washout, they will undergo locoregional therapy per institutional standards. Eventually, after a minimum 72-day washout from the end of immunotherapy, they will undergo liver transplant. Receives: Drug: Durvalumab; Drug: Tremelimumab; Procedure: Liver Transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cellular Rejection Rates
To assess the safety of immunotherapy for treatment of HCC in patients listed for a liver transplant, with respect to cellular rejection rates
Measured: Up to 30 days post transplant. The average time from consent to transplant was 11.88 months.
Secondary outcomes (6)
Adverse Events During Treatment
To assess the safety of immunotherapy for treatment of HCC in patients who have received a transplant, with respect to adverse events during treatment.
Measured: Adverse events will be collected from study drug initiation until 90 days after the last durvalumab+tremelimumab dose or before new anti-cancer therapy, whichever comes first, up to 7 months.
Radiologic Responses Via RECIST 1.1 and/or mRECIST
To assess the efficacy of immunotherapy for treatment of HCC in patients listed for a liver transplant, with respect to radiologic responses. This will be be defined the number of individuals that had complete response, partial response, or stable disease. Progressive disease will not be included. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: Timeframe includes 4 months of I/0 treatment. Radiologic responses were measured after the I/O treatment phase of the study
Pathologic Responses Via Explanted Liver Assessment
To assess the efficacy of immunotherapy for treatment of HCC in patients listed for a liver transplant, with respect to Pathologic responses. However, due to the feasibility of the trial, we were not able to collect data for this outcome.
Measured: Timeframe includes the 30 day window after a transplant.
Recurrence-free Survival and Overall Survival Outcomes Based on Survival Follow up Reporting
To assess the efficacy of immunotherapy for treatment of HCC in patients listed for a liver transplant, with respect to Survival outcomes. However, due to the feasibility of the trial, we were not able to collect data for this outcome.
Measured: Survival follow up will continue for 5 years after end of Treatment
Graft Loss
To assess the safety of immunotherapy for treatment of HCC in patients listed for a liver transplant, with respect graft loss
Measured: Day 72 post completion of immunotherapy, approximately 6.5 months
Mortality
To assess the safety of immunotherapy for treatment of HCC in patients listed for a liver transplant, with respect to mortality rates up to 30 days after transplant
Measured: Day 72 post completion of immunotherapy, approximately 7.5 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2021
- Study start7 Dec 2021
- Primary completion7 Nov 2024
- Study completion7 Nov 2024
Why it stopped: The study is closing due to low enrollment and feasibility of the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe 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
- Model description
- Single-arm, open-label, Phase II, multicenter clinical trial
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Davendra Sohal, University of Cincinnati
- Investigators
- Davendra Sohal, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05027425
- Sponsor's protocol ID
- UCCC-GI-21-01
- Status last verified
- Apr 2026
- First submitted
- 17 Aug 2021
- Last updated
- 6 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Durvalumab (MEDI4736) and Tremelimumab for Hepatocellular Carcinoma in Patients Listed for a Liver Transplant
- ClinicalTrials.gov ID
- NCT05027425
- Acronym / sponsor ID
- UCCC-GI-21-01
- Conditions
- Hepatocellular Carcinoma, Cirrhosis, Portal Hypertension
- Keywords
- Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study is closing due to low enrollment and feasibility of the study.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Study start
- 7 Dec 2021 (actual)
- Primary completion
- 7 Nov 2024 (actual)
- Study completion
- 7 Nov 2024 (actual)
- First posted
- 30 Aug 2021 (actual)
- Results
- Posted 6 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver transplant.
Detailed description
ESR-20-21010 is a single-arm, open-label, Phase II, multicenter clinical trial designed to evaluate the safety and efficacy of durvalumab and tremelimumab for the treatment of hepatocellular carcinoma (HCC) patients who have cirrhosis or portal hypertension and are evaluated by institutional Liver Transplant team and deemed eligible for transplant.
The key eligibility requirements include HCC, Child-Pugh score of up to 7, and ECOG PS of 0 or 1.
Patients will be treated with the immunotherapy combination for up to 4 months. After a minimum 28 day washout, they will undergo locoregional therapy per institutional standards. Eventually, after a minimum 72-day washout from the end of immunotherapy, they will undergo liver transplant.
The primary endpoint is proportion of patients experiencing post-transplant rejection (within 30 days of transplant). A total of 30 patients are to be enrolled, to allow at least 20 transplants for adequate primary endpoint analysis. An interim analysis after 10 patients will be performed to ensure safety. If there are untoward safety signals, study modification/discontinuation will be discussed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-arm, open-label, Phase II, multicenter clinical trial
| Arm | Type | Receives |
|---|---|---|
| Durvalumab + Tremelimumab + Liver Transplant | Experimental | Drug: Durvalumab, Drug: Tremelimumab, Procedure: Liver TransplantPatients will be treated with the immunotherapy combination for up to 4 months. After a minimum 28 day washout, they will undergo locoregional therapy per institutional standards. Eventually, after a minimum 72-day washout from the end of immunotherapy, they will undergo liver transplant. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Hepatocellular carcinoma, diagnosed either by biopsy or by combination of cirrhosis and imaging criteria (contrast-enhanced CT or MRI).
- Tumor confined to liver with no vascular invasion and no evidence of extrahepatic disease.
- Patient evaluated by institutional Liver Transplant team and listed for transplant.
- At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization.
- No prior therapy for HCC at any time.
Key exclusion criteria (31 listed)
- Extrahepatic disease.
- Variceal bleeding during 3 months prior to registration.
- Any autoimmune disease deemed a risk in the setting of immunotherapy per treating physician's judgment.
- Any other illness or patient condition deemed a medical or logistical barrier for protocol therapy per treating physician's judgment.
- Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
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 |
|---|---|---|
| DurvalumabAlso: MEDI47361500 mg IV, Q4W | Drug | Durvalumab + Tremelimumab + Liver Transplant |
| Tremelimumab300 mg IV, 1 dose on day 1 of only the first cycle | Drug | Durvalumab + Tremelimumab + Liver Transplant |
| Liver Transplantminimum 72-day washout from the end of immunotherapy, patients will undergo liver transplant. | Procedure or surgery | Durvalumab + Tremelimumab + Liver Transplant |
Primary outcome
Cellular Rejection Rates
Time frame: Up to 30 days post transplant. The average time from consent to transplant was 11.88 months.
To assess the safety of immunotherapy for treatment of HCC in patients listed for a liver transplant, with respect to cellular rejection rates
6 secondary outcomes
Adverse Events During Treatment
Time frame: Adverse events will be collected from study drug initiation until 90 days after the last durvalumab+tremelimumab dose or before new anti-cancer therapy, whichever comes first, up to 7 months.
Radiologic Responses Via RECIST 1.1 and/or mRECIST
Time frame: Timeframe includes 4 months of I/0 treatment. Radiologic responses were measured after the I/O treatment phase of the study
Pathologic Responses Via Explanted Liver Assessment
Time frame: Timeframe includes the 30 day window after a transplant.
Recurrence-free Survival and Overall Survival Outcomes Based on Survival Follow up Reporting
Time frame: Survival follow up will continue for 5 years after end of Treatment
Graft Loss
Time frame: Day 72 post completion of immunotherapy, approximately 6.5 months
Mortality
Time frame: Day 72 post completion of immunotherapy, approximately 7.5 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Davendra Sohal, MD principal investigator
University of Cincinnati
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab, Tremelimumab and Liver Transplant in people with Hepatocellular Carcinoma and Cirrhosis, run by University of Cincinnati at 3 sites 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 12 inclusion and 31 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: stopped early, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
Yes. Results are posted in the registry (first posted 6 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cellular Rejection Rates (time frame: Up to 30 days post transplant. The average time from consent to transplant was 11.88 months.). 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 6 May 2026.