Safety and Efficacy of Tremelimumab+Durvalumab(MEDI4736)+TACE in Unresectable Hepatocellular Carcinoma

NCT06911255 | Recruiting Phase 1

• 1 other identifier: DETECT
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Safety and Efficacy Evaluation of Tremelimumab Plus Durvalumab(MEDI4736) in Combination with Concurrent Transarterial Chemoembolization in Unresectable Hepatocellular carcinoma

Conditions

Hepatocellular Carcinoma (HCC); Unresectable Hepatocellular Carcinoma

Keywords

HCC Durvalumab

Outcome Measures

Primary Outcomes (1)

• PFS

  The primary endpoint for evaluating progression-free survival (PFS) will be assessed through RECIST 1.1 evaluation.

  the time from the first study treatment administration until the date of objective disease progression

Secondary Outcomes (4)

• OS

  the time from the first study treatment administration until death due to any cause, regardless of whether the patient withdraws from therapy or receives another anticancer therapy.

• ORR

  From date of enrollment until the date of first documented progression, assessed every 8 weeks up to 12 months.

• TTP

  the time from the first study treatment administration until the first confirmed tumor progression (PD) based on the RECIST 1.1 assessment.

• Safety of durvalumab and tremelimumab in terms of the occurrence of adverse events

  Until 30 days after TACE or the last dose of tremelimumab and/or durvalumab

Study Arms (1)

Tremelimumab Plus Durvalumab (MEDI4736) in Combination with Concurrent Transarterial Chemoembolizati

EXPERIMENTAL

After the intravenous (IV) administration of 300 mg of tremelimumab and 1,500 mg of durvalumab, transarterial chemoembolization (TACE) will be performed in combination with 1,500 mg of durvalumab via IV infusion every 4 weeks (Q4W) until disease progression (PD) is confirmed. TACE will be carried out 1 to 2 weeks (7 to 14 days) after the administration of tremelimumab + durvalumab, and thereafter, it will be performed as needed at the discretion of the investigator during the treatment period. If additional TACE is performed, there must be at least a 1-week interval between the additional TACE and the administration of durvalumab.

Drug: Tremelimumab Plus Durvalumab (MEDI4736); Procedure: Transarterial chemoembolization (TACE)

Interventions

Tremelimumab Plus Durvalumab (MEDI4736) DRUG

Study subjects will receive 1,500 mg of durvalumab intravenously every 4 weeks until PD is observed. However, treatment will be discontinued if unacceptable toxicity, withdrawal of consent, or any other discontinuation criteria are met. Tremelimumab will be administered first, and durvalumab infusion will begin approximately 1 hour (up to 2 hours) after the completion of tremelimumab infusion. The standard infusion time for each drug is 1 hour, but if the infusion is temporarily interrupted, the total duration should not exceed 8 hours at room temperature.

Also known as: Imfinzi®, Imjudo

Tremelimumab Plus Durvalumab (MEDI4736) in Combination with Concurrent Transarterial Chemoembolizati

Transarterial chemoembolization (TACE) PROCEDURE

TACE will be carried out 1 to 2 weeks (7 to 14 days) after the administration of tremelimumab + durvalumab, and thereafter, it will be performed as needed at the discretion of the investigator during the treatment period. If additional TACE is performed, there must be at least a 1-week interval between the additional TACE and the administration of durvalumab.

Tremelimumab Plus Durvalumab (MEDI4736) in Combination with Concurrent Transarterial Chemoembolizati

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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. Written informed consent and any locally required authorization from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• \. Male or female, aged ≥19 years at time of study entry. 3. Diagnosed with unequivocal HCC confirmed histologically or diagnosed radiologically according to American Association for the Study of Liver Diseases practice guideline.
• \. Barcelona clinic liver cancer (BCLC) staging intermediate (B) stage or BCLC advanced stage (C) HCC with or without minimal extrahepatic disease (single-organ metastasis, ≤5 metastatic lesions).
• \. Must have at least 1 untreated measurable disease (untreated target lesion i.e. a viable lesion that has never been treated with locoregional treatment \[transarterial chemoembolization {TACE}, TARE, percutaneous ethanol injection therapy, or radiofrequency ablation\]).
• \. Child-Pugh score 5 or 6 points (Child-Pugh class A). 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 8. Life expectancy of ≥ 12 weeks. 9. Body weight \>30 kg. 10. Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dL
• Absolute neutrophil count (ANC) ≥1500 per mm3
• Platelet count ≥75,000 per mm3
• Albumin ≥2.8 g/dL
• Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). (This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with the Investigator).
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤5 x institutional ULN
• 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) Females:
• Creatinine CL (mL/min)

You may not qualify if:

• \. Eligible for potentially curative treatment (surgical resection, radiofrequency ablation or immediate liver transplantation).
• \. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti- Cytotoxic T-lymphocyte- associated antigen-4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune pathways, including prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.
• \. History of organ transplantation or hematopoietic stem cell transplantation.
• \. Any other concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, papillary thyroid cancer, early gastric cancer, or other cancer for which the patient has been disease-free for at least five years.
• \. A history of a severe contrast allergy (i.e. anaphylaxis) not controlled with premedication.
• \. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product (IP) or interpretation of patient safety or study results.
• \. Participation in another clinical study with an IP during the last 8 weeks or 5 half-lives of the study drug, whichever is longer, prior to screening.
• \. 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.
• \. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤1 cycle length or 14 days, whichever is longer, prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as determined by the Investigator.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab and/or tremelimumab may be included at the discretion of the Investigator.
• \. 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.
• \. Prior hepatic radiation therapy including Total Body Irradiation (TBI) for HCC or other malignancy.
• \. 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.
• \. 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:

Sponsors & Collaborators

• Yoon Jun Kim: lead
• AstraZeneca: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

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

Study Officials

• Yoon Jun Kim, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yoon Jun Kim, MD, PhD

CONTACT

82-2-2072-3081; yoonjun@snu.ac.kr

Yun Bin Lee, MD, PhD

CONTACT

82-2-2072-2228; yblee@snu.ac.kr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Coordinating Investigator

Model Details: After the intravenous (IV) administration of 300 mg of tremelimumab and 1,500 mg of durvalumab, transarterial chemoembolization (TACE) will be performed in combination with 1,500 mg of durvalumab via IV infusion every 4 weeks (Q4W) until disease progression (PD) is confirmed. TACE will be carried out 1 to 2 weeks (7 to 14 days) after the administration of tremelimumab + durvalumab, and thereafter, it will be performed as needed at the discretion of the investigator during the treatment period. If additional TACE is performed, there must be at least a 1-week interval between the additional TACE and the administration of durvalumab.

Study Record Dates

• First Submitted: January 8, 2025
• First Posted: April 4, 2025
• Study Start: April 18, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)