Durvalumab Plus Tremelimumab as First-line Treatment in Chinese Patients With uHCC (TREMENDOUS)

An Open-label, Multi-center Phase IIIb Study of Durvalumab and Tremelimumab as First-Line Treatment in Patients With Unresectable Hepatocellular Carcinoma

This is a prospective, open label, multi-center, interventional study to assess the safety and efficacy of Druvalumab plus Tremelimumab as first-line treatment in Chinese patients with unresectable hepatocellular carcinoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Durvalumab; Drug: Tremelimumab

Detailed Description

Based on the promising result of HIMALAYA and study 22, this study is going to evaluate the efficacy and safety of Durvalumab plus Tremelimumab in Chinese population and some extended population compared to HIMALAYA, such as Child-Pugh B and, ECOG PS2.

• Study Type: Interventional
• Enrollment (Actual): 214
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100142
    • Research Site
  • Beijing, China, 100021
    • Research Site
  • Beijing, China, CN-100730
    • Research Site
  • Beijing, China, 211405
    • Research Site
  • Changsha, China, 410013
    • Research Site
  • Changsha, China, 410005
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Fuzhou, China, 350011
    • Research Site
  • Guangzhou, China, 510060
    • Research Site
  • Guangzhou, China, 510100
    • Research Site
  • Guangzhou, China, 510515
    • Research Site
  • Guangzhou, China, 510260
    • Research Site
  • Hangzhou, China, 310022
    • Research Site
  • Harbin, China, 150081
    • Research Site
  • Jinan, China, 2501117
    • Research Site
  • Nanjing, China, 2100008
    • Research Site
  • Nanjing, China, 210009
    • Research Site
  • Nanjing, China, 210029
    • Research Site
  • Ningbo, China, 315010
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shanghai, China, 200040
    • Research Site
  • Shenyang, China, 110001
    • Research Site
  • Tianjin, China, 300000
    • Research Site
  • Wenzhou, China, 325000
    • Research Site
  • Wuhan, China, 430079
    • Research Site
  • Wuhan, China, 430022
    • Research Site
  • Xi'an, China, 710038
    • Research Site
  • Zhangjiagang, China, 215699
    • Research Site
  • Zhengzhou, China, 450008
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

For inclusion in the study, patients should fulfill the following criteria:

1. Provide written informed consent to participate in the study before the start of the study
2. Age ≥18 years at the time of study entry.
3. Body weight >30 kg.
4. Confirmed HCC based on histopathological findings from tumor tissue or radiologically findings.
5. Must not have received prior systemic therapy for HCC.
6. At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. A lesion which progressed after previous ablation or TACE could be measurable if it meets these criteria.
7. Must not be eligible for locoregional therapy for unresectable HCC. For patients who progressed after locoregional therapy for HCC, locoregional therapy must have been completed ≥28 days prior to the baseline scan for the current study.
8. Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C.

9. Child-Pugh Score classification on liver disease and WHO/ECOG PS at enrolment must comply with one of the following criteria, not cumulatively:

   1. Child-Pugh Score class A with WHO/ECOG PS 0-1 at enrolment will be enrolled in cohort1;
   2. Child-Pugh class B with WHO/ECOG 0-1 will be enrolled in cohort 2;
   3. Child-Pugh class A with WHO/ECOG 2 will be enrolled in cohort 2;

Exclusion Criteria

1) Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

2）Previous study drug(s) assignment in the present study. 3）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.

4）Have received an investigational product within 28 days prior to the first dose of study drug(s).

5) Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:

• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis.

• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included (eg, hearing loss).

  6) Any concurrent chemotherapy, or biologic or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.

  7) Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

  8) Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 28 days of the first dose of study drug(s).

  9) Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study drug(s). Note: Local surgery of isolated lesions for palliative intent is acceptable.

  10) History of allogeneic organ transplantation (eg, liver transplant). 11）History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy (eg, no lactulose, rifaximin, etc. if used for purposes of hepatic encephalopathy).

  12) Clinically meaningful ascites, defined as ascites requiring increasingly frequent non-pharmacologic intervention (eg, paracentesis) and/or escalation in pharmacologic intervention to maintain symptomatic control, within 2 months prior to the first scheduled dose. Subjects on stable doses of diuretics for ascites for ≥2 months are eligible. Also, uncontrolled pleural effusion, pericardial effusion requiring recurrent drainage procedures (once monthly or more frequently) .

  13）Patients with main portal vein tumor thrombosis (Vp4). 14）Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cohort 1; durvalumab in combination with tremelimumab	Drug: Durvalumab; Durvalumab IV (intravenous infusion); Other Names: MEDI4736; Drug: Tremelimumab; Tremelimumab IV (intravenous infusion) CTLA-4 inhibitor; Other Names: There is no other names for tremelimumab.
Experimental: cohort 2; durvalumab in combination with tremelimumab	Drug: Durvalumab; Durvalumab IV (intravenous infusion); Other Names: MEDI4736; Drug: Tremelimumab; Tremelimumab IV (intravenous infusion) CTLA-4 inhibitor; Other Names: There is no other names for tremelimumab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
≥Grade 3 Adverse Events and Adverse Events of Special Interest of Cohort 1	Safety endpoint	From the time of signature of informed consent, throughout the treatment period, and up to the follow-up period, assessed up to 44months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
≥Grade 3 Adverse Events and Adverse Events of Special Interest of Cohort 2	Safety endpoint	From the time of signature of informed consent, throughout the treatment period, and up to the follow-up period, assessed up to 44 months
Overall Survival (OS)	efficacy endpoint	From the first dose of treatment to the date of death, regardless of the actual cause of the subject's death, assessed up to 44 months
Progression Free Survival (PFS) per RECIST v1.1/mRECIST	efficacy endpoint	From first dose of treatment until progression per RECIST 1.1/ mRECIST as assessed by the Investigator or death due to any cause prior to progression, assessed up to 15 months
Objective Response Rate (ORR) per RECIST 1.1/ mRECIST	efficacy endpoint	Until progression, assessed up to 15 months
Disease Control Rate (DCR) per RECIST 1.1/ mRECIST	efficacy endpoint	Until progression, assessed up to 15 months
Duration of response (DoR) per RECIST 1.1/mRECIST	efficacy endpoint	From the first dose, until progression, assessed up to 15 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: September 27, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Actual): June 26, 2026
• Last Update Submitted That Met QC Criteria: June 23, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents, Immunological; Antineoplastic Agents; durvalumab; tremelimumab
• Other Study ID Numbers: D419CR00026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient- level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

Plan Description: All request will be evaluated as per the Az disclosure commitment:

https://astrazenecaarouptrials.pharmacm.com/ST/Submission/Disclosure Yes. indicates that Az are accepting requests for IPD ,but this does not mean are quests will be shared

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitment at made to the EFPIA Pharma Data Sharing Principles .For details of our timeline please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool.

Signed Data Sharing Agreement(non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to a air access. For additional details. please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No