Hepatocellular CarcinomaPhase 2NCT02519348

A Study of Durvalumab or Tremelimumab Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Advanced Hepatocellular Carcinoma

A Phase 2 study testing Tremelimumab, Durvalumab and Bevacizumab in people with Hepatocellular Carcinoma, run by MedImmune LLC at 44 sites in 9 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This is a multicenter, open-label, stratified, randomized study to evaluate the safety, tolerability, antitumor activity, pharmacokinetics, pharmacodynamics, and immunogenicity of durvalumab or tremelimumab monotherapy, or durvalumab in combination with tremelimumab or bevacizumab in advanced hepatocellular carcinoma. Read more about this study

Who is it for?: Ages 18 to 99 years
Conditions the study is for: Hepatocellular Carcinoma
What is being tested?: Tremelimumab, Durvalumab and Bevacizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 433 participants
Where: 44 sitesin 9 countries
Study dates: 19 Oct 2015to 18 Dec 2026
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 99 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female participants
18 years and older (Japan-20 years and older)
Confirmed hepatocellular carcinoma (HCC) based on histopathological findings from tumor tissues. Advanced HCC with diagnosis confirmed pathologically or with noninvasive methods.
Immunotherapy-naïve
Have either progressed on, are intolerant to, or refused treatment with sorafenib or another approved TKI. For arm 5 only: Have not received any prior systemic therapy for HCC.

Who cannot join

Prior exposure to immune-mediated therapy
Hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy
Gastrointestinal bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
Ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose.
Main portal vein thrombosis (Vp4) as documented on imaging
Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment
Active or prior documented autoimmune or inflammatory disease with some exceptions
Current or prior use of immunosuppressive medication within 14 days with some exceptions

Trial locations and contacts

44 sites in 9 countries.

Country

City, postcode or hospital

44 sites in 9 countries

United States16 sites

Research Site
Boston, Massachusetts, 02114
Research Site
Dallas, Texas, 75390
Research Site
Durham, North Carolina, 27705
Research Site
Indianapolis, Indiana, 46202
Research Site
Jacksonville, Florida, 32224
Research Site
Nashville, Tennessee, 37203
Research Site
New Haven, Connecticut, 06510
Research Site
New York, New York, 10065
Research Site
Philadelphia, Pennsylvania, 19107
Research Site
Philadelphia, Pennsylvania, 19111
Research Site
Phoenix, Arizona, 85054
Research Site
Portland, Oregon, 97213
Research Site
San Francisco, California, 94158
Research Site
Seattle, Washington, 98109
Research Site
Stony Brook, New York, 11794
Research Site
Tampa, Florida, 33612

Other trials in United States

South Korea7 sites

Research Site
Busan, 49241
Research Site
Junggu, 41944
Research Site
Seongnam-si, 13620
Research Site
Seoul, 03080
Research Site
Seoul, 05505
Research Site
Seoul, 06273
Research Site
Seoul, 06351

Other trials in South Korea

Spain4 sites

Research Site
Barcelona, 08035
Research Site
Barcelona, 08036
Research Site
Córdoba, 14004
Research Site
Pamplona, 31008

Other trials in Spain

China3 sites

Research Site
Hangzhou, 310016
Research Site
Nanjing, 210002
Research Site
Shanghai, 200032

Other trials in China

Italy3 sites

Research Site
Benevento, 82100
Research Site
Milan, 20133
Research Site
Roma, 00168

Other trials in Italy

Japan3 sites

Research Site
Chūōku, 104-0045
Research Site
Kashiwa, 277-8577
Research Site
Osakasayama-shi, 589-8511

Other trials in Japan

Singapore3 sites

Research Site
Bukit Merah, 169610
Research Site
Singapore, 119074
Research Site
Singapore, 308433

Other trials in Singapore

Taiwan3 sites

Research Site
Kaohsiung City, 83301
Research Site
Taipei, 100
Research Site
Taoyuan City, 333

Other trials in Taiwan

Hong Kong2 sites

Research Site
Hong Kong
Research Site
Shatin

Other trials in Hong Kong

About this study

Official title: A Study of Safety, Tolerability, and Clinical Activity of Durvalumab and Tremelimumab Administered as Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Subjects With Advanced Hepatocellular Carcinoma

Read the detailed description

The study will comprise of 6 parts. Participants in Part 1A (safety run-in cohort), Part 1B (efficacy-gating cohort), Part 2A, and Part 4 will receive weight-based dosing regimens; and participants in Part 2B and Part 3 will receive fixed dosing regimens. Part 1A Stage 2 of the study may start after the first 3 participants in Stage 1 have been observed on study for at least 4 weeks. In addition, a separate cohort of participants will be enrolled in mainland China (China cohort) once global recruitment in Part 2A will be closed.

In Part 1 (both 1A and 1B), participants will receive tremelimumab 1 mg/kg intravenous (IV) every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W.
In Part 2A, participants will be randomized in a 1:1:1 ratio to receive:
Durvalumab 20 mg/kg Q4W
Tremelimumab 10 mg/kg Q4W × 7 doses followed by every 12 weeks (Q12W)
Tremelimumab 1 mg/kg Q4W × 4 doses + durvalumab 20 mg/kg Q4W, followed by durvalumab 20 mg/kg Q4W
In China cohort, Part 2A study design will be followed.
In Part 2B, participants will receive tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W.
In Part 3, participants will be randomized in a 2:2:1:2 ratio to receive:
Durvalumab 1500 mg Q4W
Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W
Tremelimumab 750 mg Q4W for 7 doses followed by Q12W
Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W, followed by durvalumab 1500 mg Q4W.

Following protocol amendment 5, enrollment into 'Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg' arm will close. Participants will be randomized at a ratio of 2:1:2 in 'Durvalumab 1500 mg Q4W', 'Tremelimumab 750 mg Q4W for 7 doses followed by Q12W', and 'Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W' arms, respectively.

In Part 4, participants will receive durvalumab 1120 mg (15 mg/kg) + bevacizumab 15 mg/kg every 3 weeks (Q3W).

Participants will receive the treatment until confirm progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.

All participants will be followed for survival until the end of study visit (last participant discontinues the study treatment).

Conditions: Hepatocellular Carcinoma
Being tested: Tremelimumab, Durvalumab, Bevacizumab
Keywords: Hepatocellular Carcinoma, Immunotherapy, Antibodies, Monoclonal, Tremelimumab, MEDI4736, Durvalumab
Medical subject headings: Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TremelimumabBiological
Tremelimumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
DurvalumabBiological
Also called MEDI4736
Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.
BevacizumabBiological
Bevacizumab 15 mg/kg will be administered by IV infusion every 3 weeks until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first.

Study groups in NCT02519348
Study group	Role	What they receive
Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg	Experimental	Participants in Part 1A (safety run-in cohort) and Part 1 B (efficacy-gating cohort) will receive tremelimumab 1 mg/kg every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Biological: Tremelimumab; Biological: Durvalumab
Parts 2 and 3: Durvalumab 1500 mg	Experimental	Participants will receive durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Biological: Durvalumab
Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg	Experimental	Participants will receive tremelimumab 300 mg 1 dose and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Biological: Tremelimumab; Biological: Durvalumab
Parts 2 and 3: Tremelimumab 750 mg	Experimental	Participants will receive tremelimumab 750 mg Q4W 7 doses followed by every 12 weeks (Q12W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Biological: Tremelimumab
Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg	Experimental	Participants will receive tremelimumab 75 mg Q4W 4 doses and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. Participant recruitment to this arm was closed following protocol amendment 5. Receives: Biological: Tremelimumab; Biological: Durvalumab
Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg	Experimental	Participants will receive durvalumab 1120 mg and bevacizumab 15 mg/kg every 3 weeks (Q3W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first Receives: Biological: Durvalumab; Biological: Bevacizumab
China Cohort: Durvalumab 20 mg/kg	Experimental	Participants will receive durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Biological: Durvalumab
China Cohort: Tremelimumab 10 mg/kg	Experimental	Participants will receive tremelimumab 10 mg/kg Q4W 7 doses followed by Q12W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Biological: Tremelimumab
China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg	Experimental	Participants will receive tremelimumab 1 mg/kg Q4W 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. Receives: Biological: Tremelimumab; Biological: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was defined as treatment-related toxicity that occurred during DLT evaluation period including: any Grade 4 immune-related adverse event (irAE), any Grade 3 colitis or any Grade 3 noninfectious pneumonitis irrespective of duration, any >= Grade 2 pneumonitis that does not resolve to <= Grade 1 within 7 days of initiation of maximal supportive care, any other Grade 3 irAE (excluding colitis or pneumonitis) that does not downgrade to Grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to <= Grade 1 or baseline within 14 days, liver transaminase elevation > 8 × upper limit of normal (ULN) or total bilirubin > 5 × ULN, aspartate aminotransferase or alanine aminotransferase > 3 × ULN with concurrent increase in total bilirubin > 2 × ULN without evidence of cholestasis or alternative explanations, and any >= Grade 3 non-irAE (except for the protocol stated conditions).
Measured: From Day 1 to Day 28 after first dose of study drug
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measure at the time of end of study.
Measured: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters
Participants with clinically important Common Terminology Criteria for Adverse Events (CTCAE) grade changes to 3 or 4 in hematology and chemistry parameters are reported. There will be no updated results for this outcome measure at the time of end of study.
Measured: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Vital sign assessment included pulse rate, blood pressure, temperature, weight, and respiratory rate. Vital signs abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study.
Measured: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events
Number of participants with ECG abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study.
Measured: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)

Secondary outcomes (7)

Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR)
Disease assessments based on investigator assessments and BICR review were determined by using Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) guidelines. The ORR is defined as best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR). The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. There will be no updated results for this outcome measure at the time of end of study.
Measured: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Disease Control Rate (DCR) Based on Investigator Assessments and BICR
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The DCR is defined as a BOR of confirmed CR, confirmed PR, or stable disease (SD). A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. There will be no updated results for this outcome measure at the time of end of study.
Measured: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Time to Response (TTR) Based on Investigator Assessments and BICR
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The TTR is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR). A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study.
Measured: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Duration of Response (DoR) Based on Investigator Assessments and BICR
The DoR is defined as the time from the date of first documented OR (confirmed CR or confirmed PR) until date of documented progression (PD) based on investigator assessments and BICR review by using RECIST v1.1 or death in absence of disease progression. A confirmed CR is defined in above outcome measures. The PD is defined at least 20% increase in sum of diameters of target lesions (compared with nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. For participants who were alive and no documented PD at the time of data cutoff for analysis, DoR was censored at the last evaluable disease assessment date. The DoR was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study.
Measured: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Time to Progression (TTP) Based on Investigator Assessments and BICR
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The TTP was defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 to the first documentation of radiographic disease progression. However, if the participant died without tumor progression, they were censored at the time of death. Participants with no documented PD by the data cutoff date for TTP analysis were censored at the date of their last evaluable disease assessment. The TTP was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study.
Measured: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Progression Free Survival (PFS) Based on Investigator Assessments and BICR
Disease assessments based on investigator assessments and BICR review were determined by using RECIST v1.1 guidelines. The PFS is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until the first documentation of radiographic disease progression or death due to any cause, whichever occurs first. The PD is defined at least 20% increase in the sum of diameters of target lesions (compared with the nadir at 2 consecutive visits with an absolute increase of 5 mm), unequivocal progression of existing non-target lesions or new lesion. Participants who were alive with no documented PD by the data cutoff date for PFS analysis were censored at the date of their last evaluable disease assessment. The PFS was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study.
Measured: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Overall Survival (OS)
The OS is defined as the time from randomization for Parts 2A and 3, and time from first dose for Parts 1, 2B, and 4 until death due to any cause. If there was no death reported for a participant by the data cut-off date for overall survival analysis, OS was censored at the last known alive date. The OS was estimated using Kaplan-Meier method. There will be no updated results for this outcome measure at the time of end of study.
Measured: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Oct 201518 Dec 2026

First posted10 Aug 2015 (estimated)
Study start19 Oct 2015
Primary completion6 Nov 2020
Study completion18 Dec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 433 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02519348
Sponsor's protocol ID: D4190C00022
Other IDs: 2024-517085-41-00, 2015-001663-39, 2015
Status last verified: Aug 2026
First submitted: 30 Jul 2015
Last updated: 5 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

Publications

Kelley RK, Sangro B, Harris W, Ikeda M, Okusaka T, Kang YK, Qin S, Tai DW, Lim HY, Yau T, Yong WP, Cheng AL, Gasbarrini A, Damian S, Bruix J, Borad M, Bendell J, Kim TY, Standifer N, He P, Makowsky M, Negro A, Kudo M, Abou-Alfa GK. Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. J Clin Oncol. 2021 Sep 20;39(27):2991-3001. doi: 10.1200/JCO.20.03555. Epub 2021 Jul 22.
PubMed 34292792

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 5 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Study of Safety, Tolerability, and Clinical Activity of Durvalumab and Tremelimumab Administered as Monotherapy, or Durvalumab in Combination With Tremelimumab or Bevacizumab in Subjects With Advanced Hepatocellular Carcinoma
ClinicalTrials.gov ID: NCT02519348
Acronym / sponsor ID: D4190C00022
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma, Immunotherapy, Antibodies, Monoclonal, Tremelimumab, MEDI4736, Durvalumab
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 433 participants (actual)
Lead sponsor: MedImmune LLCIndustry (pharma, biotech, devices)
Study start: 19 Oct 2015 (actual)
Primary completion: 6 Nov 2020 (actual)
Study completion: 18 Dec 2026 (estimated)
First posted: 10 Aug 2015 (estimated)
Results: Posted 6 Dec 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

In Part 1 (both 1A and 1B), participants will receive tremelimumab 1 mg/kg intravenous (IV) every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W.
In Part 2A, participants will be randomized in a 1:1:1 ratio to receive:
Durvalumab 20 mg/kg Q4W
Tremelimumab 10 mg/kg Q4W × 7 doses followed by every 12 weeks (Q12W)
Tremelimumab 1 mg/kg Q4W × 4 doses + durvalumab 20 mg/kg Q4W, followed by durvalumab 20 mg/kg Q4W
In China cohort, Part 2A study design will be followed.
In Part 2B, participants will receive tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W.
In Part 3, participants will be randomized in a 2:2:1:2 ratio to receive:
Durvalumab 1500 mg Q4W
Tremelimumab 300 mg × 1 dose + durvalumab 1500 mg Q4W
Tremelimumab 750 mg Q4W for 7 doses followed by Q12W
Tremelimumab 75 mg Q4W × 4 doses + durvalumab 1500 mg Q4W, followed by durvalumab 1500 mg Q4W.

In Part 4, participants will receive durvalumab 1120 mg (15 mg/kg) + bevacizumab 15 mg/kg every 3 weeks (Q3W).

All participants will be followed for survival until the end of study visit (last participant discontinues the study treatment).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 9

Arm	Type	Receives
Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg	Experimental	Biological: Tremelimumab, Biological: DurvalumabParticipants in Part 1A (safety run-in cohort) and Part 1 B (efficacy-gating cohort) will receive tremelimumab 1 mg/kg every 4 weeks (Q4W) 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
Parts 2 and 3: Durvalumab 1500 mg	Experimental	Biological: DurvalumabParticipants will receive durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg	Experimental	Biological: Tremelimumab, Biological: DurvalumabParticipants will receive tremelimumab 300 mg 1 dose and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow, or development of other reason for treatment discontinuation, whichever occurs first.
Parts 2 and 3: Tremelimumab 750 mg	Experimental	Biological: TremelimumabParticipants will receive tremelimumab 750 mg Q4W 7 doses followed by every 12 weeks (Q12W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg	Experimental	Biological: Tremelimumab, Biological: DurvalumabParticipants will receive tremelimumab 75 mg Q4W 4 doses and durvalumab 1500 mg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first. Participant recruitment to this arm was closed following protocol amendment 5.
Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg	Experimental	Biological: Durvalumab, Biological: BevacizumabParticipants will receive durvalumab 1120 mg and bevacizumab 15 mg/kg every 3 weeks (Q3W) until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first
China Cohort: Durvalumab 20 mg/kg	Experimental	Biological: DurvalumabParticipants will receive durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
China Cohort: Tremelimumab 10 mg/kg	Experimental	Biological: TremelimumabParticipants will receive tremelimumab 10 mg/kg Q4W 7 doses followed by Q12W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.
China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg	Experimental	Biological: Tremelimumab, Biological: DurvalumabParticipants will receive tremelimumab 1 mg/kg Q4W 4 doses and durvalumab 20 mg/kg Q4W until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurs first.

Who may qualify

Ages: 18 to 99 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Male or female participants
18 years and older (Japan-20 years and older)
Confirmed hepatocellular carcinoma (HCC) based on histopathological findings from tumor tissues. Advanced HCC with diagnosis confirmed pathologically or with noninvasive methods.
Immunotherapy-naïve
Have either progressed on, are intolerant to, or refused treatment with sorafenib or another approved TKI. For arm 5 only: Have not received any prior systemic therapy for HCC.

Key exclusion criteria (8 listed)

Prior exposure to immune-mediated therapy
Hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy
Gastrointestinal bleeding (eg, esophageal varices or ulcer bleeding) within 12 months
Ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose.
Main portal vein thrombosis (Vp4) as documented on imaging

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TremelimumabTremelimumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.	Biological	China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg, China Cohort: Tremelimumab 10 mg/kg, Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg, Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg, Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg, Parts 2 and 3: Tremelimumab 750 mg
DurvalumabAlso: MEDI4736Durvalumab will be administered by IV infusion according to doses and frequency mentioned in arms' description.	Biological	China Cohort: Durvalumab 20 mg/kg, China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg, Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg, Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg, Parts 2 and 3: Durvalumab 1500 mg, Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg, Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg
BevacizumabBevacizumab 15 mg/kg will be administered by IV infusion every 3 weeks until confirmed progressive disease, withdrawal of consent, lost to follow-up, or development of other reason for treatment discontinuation, whichever occurred first.	Biological	Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg

Primary outcome

Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: From Day 1 to Day 28 after first dose of study drug
A DLT was defined as treatment-related toxicity that occurred during DLT evaluation period including: any Grade 4 immune-related adverse event (irAE), any Grade 3 colitis or any Grade 3 noninfectious pneumonitis irrespective of duration, any >= Grade 2 pneumonitis that does not resolve to <= Grade 1 within 7 days of initiation of maximal supportive care, any other Grade 3 irAE (excluding colitis or pneumonitis) that does not downgrade to Grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to <= Grade 1 or baseline within 14 days, liver transaminase elevation > 8 × upper limit of normal (ULN) or total bilirubin > 5 × ULN, aspartate aminotransferase or alanine aminotransferase > 3 × ULN with concurrent increase in total bilirubin > 2 × ULN without evidence of cholestasis or alternative explanations, and any >= Grade 3 non-irAE (except for the protocol stated conditions).
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measure at the time of end of study.
Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Participants with clinically important Common Terminology Criteria for Adverse Events (CTCAE) grade changes to 3 or 4 in hematology and chemistry parameters are reported. There will be no updated results for this outcome measure at the time of end of study.
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Vital sign assessment included pulse rate, blood pressure, temperature, weight, and respiratory rate. Vital signs abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study.
Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as Treatment-Emergent Adverse Events
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Number of participants with ECG abnormalities recorded as TEAEs are reported. There will be no updated results for this outcome measure at the time of end of study.

7 secondary outcomes

Overall Objective Response Rate (ORR) Based on Investigator Assessments and Blinded Independent Central Review (BICR)
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Disease Control Rate (DCR) Based on Investigator Assessments and BICR
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Time to Response (TTR) Based on Investigator Assessments and BICR
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Duration of Response (DoR) Based on Investigator Assessments and BICR
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Time to Progression (TTP) Based on Investigator Assessments and BICR
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Progression Free Survival (PFS) Based on Investigator Assessments and BICR
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)
Overall Survival (OS)
Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months)

Results and safety

Results posted to the registry on 6 Dec 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg	40	0
Parts 2 and 3: Durvalumab 1500 mg	104	0
Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg	75	0
Parts 2 and 3: Tremelimumab 750 mg	69	0
Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg	84	0
Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg	47	0
China Cohort: Durvalumab 20 mg/kg	3	0
China Cohort: Tremelimumab 10 mg/kg	5	0
China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg	6	0

Primary outcome: Number of Participants With Dose Limiting Toxicities (DLTs)

Time frame: From Day 1 to Day 28 after first dose of study drug. Count of participants. Unit: Participants

Measure	Part 1A: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg n = 16
Value	0

Population analysed: DLT evaluable set included all Part 1A participants who received at least 1 dose of study drug and completed the safety follow-up through the DLT evaluation period (Days 1 to 28 after first dose of study drug) or experienced any DLT.

Primary outcome: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months). Count of participants. Unit: Participants

Measure	Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg n = 40	Parts 2 and 3: Durvalumab 1500 mg n = 101	Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg n = 74	Parts 2 and 3: Tremelimumab 750 mg n = 69	Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg n = 82	Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg n = 47	China Cohort: Durvalumab 20 mg/kg n = 3	China Cohort: Tremelimumab 10 mg/kg n = 5	China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg n = 5
Any TEAEs	38	95	73	67	80	45	3	5	5
Any TESAEs	22	45	32	36	37	17	1	3	4

Population analysed: Safety analysis set included all participants who received at least one dose of study drug.

Primary outcome: Number of Participants With Clinically Important Changes in Hematology and Clinical Chemistry Parameters

Measure	Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg n = 39	Parts 2 and 3: Durvalumab 1500 mg n = 100	Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg n = 74	Parts 2 and 3: Tremelimumab 750 mg n = 68	Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg n = 81	Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg n = 46	China Cohort: Durvalumab 20 mg/kg n = 3	China Cohort: Tremelimumab 10 mg/kg n = 5	China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg n = 4
Hemoglobin	0	5	6	6	6	0	0	1	1
Leukocytes	1	1	1	1	2	1	0	0	0
Lymphocytes	3	7	10	4	8	2	0	1	0
Neutrophils	0	1	1	0	0	1	0	0	0
Platelets	3	5	0	2	4	3	1	0	0
Activated Partial Thromboplastin Time	0	0	0	0	1	1	0	0	0
Fibrinogen	5	5	5	2	5	3	0	0	0
Prothrombin Intl. Normalized Ratio	0	1	3	1

Primary outcome: Number of Participants With Abnormal Vital Signs Reported as TEAEs

Measure	Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg n = 40	Parts 2 and 3: Durvalumab 1500 mg n = 101	Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg n = 74	Parts 2 and 3: Tremelimumab 750 mg n = 69	Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg n = 82	Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg n = 47	China Cohort: Durvalumab 20 mg/kg n = 3	China Cohort: Tremelimumab 10 mg/kg n = 5	China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg n = 5
Hypertension	1	4	4	2	3	6	0	0	0
Hypotension	0	4	0	3	2	0	0	0	0
Systolic hypertension	0	1	0	0	0	0	0	0	0
Weight decreased	4	4	4	4	4	2	0	0	1
Weight increased	2	0	1	1	2	0	0	0	0
Palpitations	1	0	0	0	0	0	1	0	0
Pyrexia	6	6	14	9	14	4	2	2	1

Population analysed: Safety analysis set included all participants who received at least one dose of study drug.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Day 1 through the 12 months after the first dose of study drug given to the last participant enrolled in the study (approximately 61 months). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg	22 of 40 (55%)	37 of 40 (92.5%)	31 of 40
Parts 2 and 3: Durvalumab 1500 mg	45 of 101 (44.6%)	92 of 101 (91.1%)	78 of 104
Parts 2 and 3: Tremelimumab 300 mg + Durvalumab 1500 mg	32 of 74 (43.2%)	73 of 74 (98.6%)	49 of 75
Parts 2 and 3: Tremelimumab 750 mg	36 of 69 (52.2%)	66 of 69 (95.7%)	55 of 69
Parts 2 and 3: Tremelimumab 75 mg + Durvalumab 1500 mg	37 of 82 (45.1%)	80 of 82 (97.6%)	64 of 84
Part 4: Durvalumab 1120 mg + Bevacizumab 15 mg/kg	17 of 47 (36.2%)	45 of 47 (95.7%)	18 of 47
China Cohort: Durvalumab 20 mg/kg	1 of 3 (33.3%)	3 of 3 (100%)	2 of 3
China Cohort: Tremelimumab 10 mg/kg	3 of 5 (60%)	5 of 5 (100%)	5 of 5
China Cohort: Tremelimumab 1 mg/kg + Durvalumab 20 mg/kg	4 of 5 (80%)	5 of 5 (100%)	5 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34292792Kelley RK, Sangro B, Harris W, Ikeda M, Okusaka T, Kang YK, Qin S, Tai DW, Lim HY, Yau T, Yong WP, Cheng AL, Gasbarrini A, Damian S, Bruix J, Borad M, Bendell J, Kim TY, Standifer N, He P, Makowsky M, Negro A, Kudo M, Abou-Alfa GK. Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study. J Clin Oncol. 2021 Sep 20;39(27):2991-3001. doi: 10.1200/JCO.20.03555. Epub 2021 Jul 22.
Related InfoLink provided by the sponsor.
Related InfoLink provided by the sponsor.
Related InfoLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MedImmune, LLC MedImmune, LLC study director

MedImmune LLC

44 sites in 9 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tremelimumab, Durvalumab and Bevacizumab in people with Hepatocellular Carcinoma, run by MedImmune LLC at 44 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 5 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in United States, South Korea, Spain, China, Italy and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: From Day 1 to Day 28 after first dose of study drug). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02519348, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2026.