Durvalumab (MEDI4736) and Tremelimumab for Hepatocellular Carcinoma in Patients Listed for a Liver Transplant

NCT05027425 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: UCCC-GI-21-01
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 3

Brief Summary

Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver transplant.

Conditions

Hepatocellular Carcinoma; Cirrhosis; Portal Hypertension

Keywords

Transplant

Outcome Measures

Primary Outcomes (1)

• 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

  Up to 30 days post transplant. The average time from consent to transplant was 11.88 months.

Secondary Outcomes (6)

• Adverse Events During Treatment

  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

  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

  Timeframe includes the 30 day window after a transplant.

• Recurrence-free Survival and Overall Survival Outcomes Based on Survival Follow up Reporting

  Survival follow up will continue for 5 years after end of Treatment

• Graft Loss

  Day 72 post completion of immunotherapy, approximately 6.5 months

Study Arms (1)

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.

Drug: Durvalumab; Drug: Tremelimumab; Procedure: Liver Transplant

Interventions

Durvalumab DRUG

1500 mg IV, Q4W

Also known as: MEDI4736

Durvalumab + Tremelimumab + Liver Transplant

Tremelimumab DRUG

300 mg IV, 1 dose on day 1 of only the first cycle

Durvalumab + Tremelimumab + Liver Transplant

Liver Transplant PROCEDURE

minimum 72-day washout from the end of immunotherapy, patients will undergo liver transplant.

Durvalumab + Tremelimumab + Liver Transplant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• University of Cincinnati: lead

Study Sites (3)

Washington University School of Medicine

St Louis, Missouri, 63130, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Simmons Comprehensive Cancer Center UT Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Fibrosis; Hypertension, Portal

Interventions

durvalumab; tremelimumab; Liver Transplantation

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Digestive System Surgical Procedures; Surgical Procedures, Operative; Organ Transplantation; Transplantation

Results Point of Contact

• Title: Dr. Davendra Sohal
• Organization: University of Cincinnati Cancer Center

sohalda@ucmail.uc.edu

+1 513 558 2361

Study Officials

• Davendra Sohal, MD

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Single-arm, open-label, Phase II, multicenter clinical trial

Study Record Dates

• First Submitted: August 17, 2021
• First Posted: August 30, 2021
• Study Start: December 7, 2021
• Primary Completion: November 7, 2024
• Study Completion: November 7, 2024
• Last Updated: May 6, 2026
• Results First Posted: May 6, 2026

Record last verified: 2026-04

Locations

US (3)