Durvalumab and Tremelimumab as First Line Treatment in Participants With Advanced Hepatocellular Carcinoma (HCC)

NCT05883644 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: D419CR000302022-502012-37-00
• Study Type: interventional
• Target: 111
• Locations: 10 countries
• Sites: 40

Brief Summary

This study will assess the safety and efficacy of Single Tremelimumab Regular Interval Durvalumab (STRIDE) as first-line therapy in participants with advanced unresectable HCC.

Conditions

Advanced Hepatocellular Carcinoma

Keywords

liver cancer; human mAb; immunoglobulin G1 kappa subclass; STRIDE; Barcelona Clinic Liver Cancer (BCLC); Child-Pugh

Outcome Measures

Primary Outcomes (2)

• Incidence of grade 3 or 4 possibly related to treatment adverse events (PRAEs)

  PRAE is defined as an AE which has been assessed by the investigator to be possibly related to IMP.

  From the date of first dose of IMP until 6 months after the initiation of study intervention

• Objective response rate (ORR)

  ORR is defined as the number (%) of participants with a confirmed objective tumour response (complete response \[CR\] or partial response \[PR\]) as determined by the investigator per Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1).

  From the first dose of IMP until progression, or the last evaluable assessment in the absence of progression [approx. up to 33 months]

Secondary Outcomes (15)

• Number of participants with adverse events (AEs), serious adverse events (SAEs), adverse event of special interest (AESIs), immune-mediated AEs (imAEs)

  From screening until 90 days following discontinuation of the last dose of IMP [approx. up to 33 months]

• Overall Survival (OS)

  From the date of the first dose of IMP until death [maximum follow-up approx. 33 months]

• Progression-Free Survival (PFS)

  From the date of the first dose of IMP until the date of objective PD or death [maximum follow-up approx. 33 months]

• Disease Control Rate at Week 16 (DCR-16w)

  At Week 16

• Disease Control Rate at Week 24 (DCR-24w)

  At Week 24

Study Arms (1)

Durvalumab plus Tremelimumab

EXPERIMENTAL

Participants will receive a single priming dose of Tremelimumab plus Durvalumab at Day 1 (Week 0), followed by Durvalumab monotherapy starting at Week 4 and continuing until clinical progression, confirmed RECIST 1.1-defined radiological progression, unacceptable toxicity, withdrawal of consent, or any intervention discontinuation criteria.

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

Participants will receive 1500 mg at Day 1 and later receive as monotherapy starting at Week 4 for every 4 weeks through IV infusion

Durvalumab plus Tremelimumab

Tremelimumab DRUG

Participants will receive single dose of 300 mg through IV infusion at Day 1

Durvalumab plus Tremelimumab

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed unresectable HCC based on histopathological findings (prior histological verification confirming HCC is acceptable), or radiological findings in participants with cirrhosis where histopathological confirmation is not clinically feasible
• Must not have received prior systemic therapy for HCC
• Participants expected to live 12 weeks or more
• At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter with CT or MRI, and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines
• Must not be eligible for LRT for unresectable HCC.
• Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy LRT) or stage C
• Child-Pugh Score classification on liver disease and WHO/ECOG PS at enrolment complying one of the following:
• Child-Pugh score B7 or B8 with a WHO/ECOG PS of 0-1 at enrolment, without main trunk portal vein thrombosis.
• Child-Pugh class A with a WHO/ECOG PS of 2 at enrolment, without main trunk portal vein thrombosis (ie, ECOG PS 2 participants with main portal vein tumour thrombosis are excluded from this study).
• Child-Pugh class A with WHO/ECOG PS of 0-1 at enrolment and with chronic main trunk portal vein thrombosis
• Participants with hepatitis B virus (HBV) infection must be treated with antiviral therapy prior to enrolment.
• Participants with hepatitis C virus (HCV) infection must have confirmed diagnosis of HCV characterized by the presence of detectable HCV RNA or anti-HCV upon enrolment
• Adequate organ and bone marrow function
• Negative pregnancy test (serum) for women of childbearing potential.
• Female participants must be 1 year post-menopausal, surgically sterile, or using one highly effective form of birth control

You may not qualify if:

• Any evidence of acute or uncontrolled diseases, chronic diverticulitis or previous complicated diverticulitis, or history of allogeneic organ transplant, which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol
• Refractory nausea and vomiting, chronic gastrointestinal (GI) disease, inability to swallow a formulated product, or previous significant bowel resection
• History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia
• History of another primary malignancy except for:
• Malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence, or
• Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or lentigo maligna that has undergone potentially curative therapy, or
• Adequately treated carcinoma in situ without evidence of disease
• Persistent toxicities (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade \> 1) caused by previous anticancer therapy
• Active or prior documented autoimmune or inflammatory disorders, autoimmune pneumonitis, and autoimmune myocarditis
• History of active primary immunodeficiency
• History of leptomeningeal carcinomatosis
• History of hepatic encephalopathy within the past 6 months or requirement for medications to prevent or control encephalopathy
• Active or prior documented GI bleeding (eg. esophageal varices or ulcer bleeding) within the past 6 months.
• Clinical judgement of acute main trunk portal vein thrombosis
• History of previous, or current, brain metastases or spinal cord compression

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (40)

Research Site

La Jolla, California, 92093, United States

Location

Research Site

Shreveport, Louisiana, 71103, United States

Location

Research Site

Detroit, Michigan, 48202, United States

Location

Research Site

Bobigny, 93000, France

Location

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Clichy, 92110, France

Location

Research Site

Créteil, 94010, France

Location

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Marseille, 13005, France

Location

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Rennes, 35000, France

Location

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Berlin, D-13353, Germany

Location

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Cologne, 50937, Germany

Location

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Frankfurt, 60488, Germany

Location

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Lübeck, 23538, Germany

Location

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Hong Kong, 0000, Hong Kong

Location

Research Site

Shatin, 00000, Hong Kong

Location

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Milan, 20132, Italy

Location

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Naples, 80147, Italy

Location

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Padova, 35128, Italy

Location

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Pisa, 56126, Italy

Location

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Rozzano, 20089, Italy

Location

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Turin, 10128, Italy

Location

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Kanazawa, 920-8641, Japan

Location

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Kashiwa, 277-8577, Japan

Location

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Matsuyama, 790-0024, Japan

Location

Research Site

Musashino-shi, 180-8610, Japan

Location

Research Site

Osakasayama-shi, 589-8511, Japan

Location

Research Site

Yokohama, 241-8515, Japan

Location

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Singapore, 119228, Singapore

Location

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Singapore, 169610, Singapore

Location

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Singapore, 308433, Singapore

Location

Research Site

Gyeonggi-do, 13620, South Korea

Location

Research Site

Seongnam-si, 13496, South Korea

Location

Research Site

Seoul, 03722, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Research Site

Seoul, 06351, South Korea

Location

Research Site

Barcelona, 8035, Spain

Location

Research Site

Córdoba, 14004, Spain

Location

Research Site

Madrid, 28007, Spain

Location

Research Site

Madrid, 28040, Spain

Location

Research Site

Pamplona, 31008, Spain

Location

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Hanoi, 100000, Vietnam

Location

MeSH Terms

Conditions

Liver Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Study Officials

• Stephen Chan, MD

  Department of Clinical Oncology, Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

• Lorenza Rimassa, MD

  Humanitas Cancer Centre, IRCCS Humanitas Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase IIIb Non-randomised and non-blinded single arm study

Study Record Dates

• First Submitted: May 22, 2023
• First Posted: June 1, 2023
• Study Start: June 27, 2023
• Primary Completion: March 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• 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 gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

HK (2); DE (4); JP (6); IT (6); KR (5); US (3); FR (5); ES (5); VN (1); SG (3)