Study of Tremelimumab and Durvalumab (MEDI4736) (T300+D) in Advanced Hepatocellular Carcinomas With Child-Pugh-B Cirrhosis

NCT06526104 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CTMS# 23-0164STUDY00001088
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, phase II study of patients with advanced liver cancer or hepatocellular carcinoma (HCC) who are eligible for first-line treatment with T300+D. The invesitgators hypothesize that T300+D will be safe and tolerated in CP-B patients with HCC. HCC mostly affects disadvantaged populations with higher rates among racial/ethnic minorities, who are often not included in clinical trials (i.e., Hispanics, Blacks, underserved, low socioeconomic status) and present with more severe disease. Given there is not much data in the US patient cohort, this study provides a chance to gain that knowledge.

Conditions

Cirrhosis, Liver; Hepatocellular Carcinoma

Keywords

Tremelimumab; Durvalumab; Child-Pugh-B Cirrhosis

Outcome Measures

Primary Outcomes (1)

• Grade 3 or Higher Treatment Related Treatment Emergent-Adverse Events (TRTE-AEs)

  The number and grade 1-5 of all adverse events will be documented according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0; measured at baseline, each cycle, and up to 90 days after treatment discontinued. Grade 3 and higher TRTE-AEs will be reported for this outcome.

  Baseline up to 1 year

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Baseline to 1 year

• Progression Free Survival (PFS)

  Baseline to 1 year

• Overall Survival (OS)

  Baseline to 1 year

• Albumin-Bilirubin (ALBI) grade

  Baseline to 1 year

Other Outcomes (2)

• European Organisation For Research and Treatment of Cancer (EORTC)- Quality of Life Questionnaire (QLC)

  Baseline up to 16 weeks

• EORTC QLQ-HCC18 (18-item hepatocellular cancer health-related quality of life questionnaire)

  Baseline to 16 weeks

Study Arms (1)

Stride (Single T Regular Interval D) Arm

EXPERIMENTAL

Tremelimumab dosed once at the beginning of the first cycle, 300mg IV infusion and Durvalumab 1500mg IV dosed with the first dose of Tremelimumab and then once per cycle (every 4 weeks)

Drug: Tremelimumab; Drug: Durvalumab

Interventions

Tremelimumab DRUG

Priming dose of tremelimumab 300 mg IV once (Cycle 1, Day 1 only)

Also known as: Imjudo

Stride (Single T Regular Interval D) Arm

Durvalumab DRUG

Durvalumab 1500 mg IV on Day 1 of each 4-week cycle.

Also known as: Imfinzi

Stride (Single T Regular Interval D) Arm

Eligibility Criteria

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

You may qualify if:

• Patients diagnosed with HCC based on pathologic diagnosis from biopsy or radiographic diagnosis on CT liver or MRI liver (i.e., Barcelona Clinic Liver Cancer (BCLC) stage B and not candidate for locoregional therapies or BCLC stage C)10
• Patients with Child-Pugh-B7 or -B8 liver cirrhosis11
• ECOG performance status score 0-1
• Patients with Hepatitis B Virus (HBV) infection are required to receive effective antiviral therapy and have a viral load less than 500 IU/mL at screening; antiviral therapy is not required for patients with Hepatitis C Virus (HCV) infection.
• Adequate organ and bone marrow function:
• Absolute neutrophil counts ≥1000/uL
• Platelets ≥60 × 100/uL
• Hemoglobin ≥8.0 g/dL
• ALT and AST ≤5× upper limit of normal each
• Bilirubin ≤3 mg/dL,
• International normalized ratio (INR) ≤2.3 or prothrombin time ≤6 seconds above control)
• Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine clearance CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min)=Weight (kg) x (140 - Age) /72 x serum creatinine (mg/dL)
• Females:

You may not qualify if:

• Patients who are candidates for curative treatments
• History of uncontrolled hepatic encephalopathy in the past 6 months; patients who are stable on medical therapy are eligible.
• Active substance abuse or alcohol abuse at the time of consent or enrollment, which in the opinion of the treating physician would interfere with the safety of the patient and/or adherence to the study protocol.
• Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Prior systemic therapy for locally advanced or metastatic HCC
• Participation in another clinical study with an investigational product during the last 1 month.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. \<\<amend as required based on any combination studies with other anticancer agents\>\>
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
• 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
• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• AstraZeneca: collaborator

Study Sites (1)

UT Health San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Cirrhosis

Interventions

tremelimumab; durvalumab

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; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sukeshi Arora, MD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Epp Goodwin

CONTACT

210-450-5798; goodwine@uthscsa.edu

Sukeshi Arora, MD

CONTACT

210-450-2872; aroras@uthscsa.edu

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: Principal Investigator

Model Details: This is a single-arm, phase II study of patients with advanced HCC with Child-Pugh B cirrhosis who are eligible for first-line treatment with T300+D.

Study Record Dates

• First Submitted: July 23, 2024
• First Posted: July 29, 2024
• Study Start: December 2, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: At the completion of the study at the time of publication in a peer review journal.

Locations

US (1)