Advanced Hepatocellular CarcinomaPhase 3SIERRANCT05883644
Durvalumab and Tremelimumab as First Line Treatment in Participants With Advanced Hepatocellular Carcinoma (HCC)
A Phase 3 study testing Durvalumab and Tremelimumab in people with Advanced Hepatocellular Carcinoma, run by AstraZeneca at 40 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Advanced Hepatocellular Carcinoma
- What is being tested?
- Durvalumab and Tremelimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 111 participants
- Where
- 40 sitesin 10 countries
- Study dates
- 27 Jun 2023to 30 Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 17Show fewer
- 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
- Male and Female participants and their partners must use an acceptable method of contraception.
- Body weight >30 kg
Who cannot join
- 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
Show all 23Show fewer
- 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
- Known fibrolamellar hepatocellular carcinoma (HCC), sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Clinically meaningful ascites
- Participants co-infected with HBV and HCV or co-infected with HBV and hepatitis D virus (HDV)
- Known to have tested positive for human immunodeficiency virus (HIV) or active tuberculosis infection
- Any concomitant medication known to be associated with Torsades de Pointes
- Prior exposure to immune-mediated therapy excluding therapeutic anticancer vaccines
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab
- Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention" and "Major surgical procedure (as defined by the investigator) or significant traumatic injury within 4 weeks of the first dose of study intervention.
Trial locations and contacts
40 sites in 10 countries.
40 sites in 10 countries
Italy6 sites
Research Site
Milan, 20132
Research Site
Naples, 80147
Research Site
Padova, 35128
Research Site
Pisa, 56126
Research Site
Rozzano, 20089
Research Site
Turin, 10128
Japan6 sites
Research Site
Kanazawa, 920-8641
Research Site
Kashiwa, 277-8577
Research Site
Matsuyama, 790-0024
Research Site
Musashino-shi, 180-8610
Research Site
Osakasayama-shi, 589-8511
Research Site
Yokohama, 241-8515
France5 sites
Research Site
Bobigny, 93000
Research Site
Clichy, 92110
Research Site
Créteil, 94010
Research Site
Marseille, 13005
Research Site
Rennes, 35000
South Korea5 sites
Research Site
Gyeonggi-do, 13620
Research Site
Seongnam-si, 13496
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Spain5 sites
Research Site
Barcelona, 8035
Research Site
Córdoba, 14004
Research Site
Madrid, 28007
Research Site
Madrid, 28040
Research Site
Pamplona, 31008
Germany4 sites
Research Site
Berlin, D-13353
Research Site
Cologne, 50937
Research Site
Frankfurt, 60488
Research Site
Lübeck, 23538
United States3 sites
Research Site
Detroit, Michigan, 48202
Research Site
La Jolla, California, 92093
Research Site
Shreveport, Louisiana, 71103
Singapore3 sites
Research Site
Singapore, 119228
Research Site
Singapore, 169610
Research Site
Singapore, 308433
Hong Kong2 sites
Research Site
Hong Kong, 0000
Research Site
Hong Kong, 999077
About this study
Official title: A Phase IIIb Single Arm, Open-label, Multicentre Study of Durvalumab and Tremelimumab as First Line Treatment in Participants With Advanced Hepatocellular Carcinoma (SIERRA)
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.
Read the detailed description
This is a Phase IIIb, open-label, single arm, multicentre study to assess the safety and efficacy of STRIDE as first-line therapy in participants with advanced unresectable HCC who have one of the following:
- Child-Pugh score B7 or B8 with a World Health Organisation Eastern Cooperative Oncology Group Performance Status (WHO/ECOG PS) of 0-1 at enrolment, or
- Child-Pugh class A with a WHO/ECOG PS of 2 at enrolment, or
- Child-Pugh class A with a WHO/ECOG PS of 0-1 and with evidence of chronic main trunk portal vein thrombosis at enrolment
Participants must not have received any prior systemic therapy for HCC. Participants may have previously received locoregional therapy (LRT) but must no longer be suitable for additional LRT. Any local treatment needs to have been completed at least 4 weeks prior to initiation of treatment. The study consists of 4 periods: screening (Day-28 to Day -1), Treatment period, safety follow-up and survival follow-up.
- Conditions
- Advanced Hepatocellular Carcinoma
- Being tested
- Durvalumab, Tremelimumab
- Keywords
- liver cancer, human mAb, immunoglobulin G1 kappa subclass, STRIDE, Barcelona Clinic Liver Cancer (BCLC), Child-Pugh
- Medical subject headings
- Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Participants will receive 1500 mg at Day 1 and later receive as monotherapy starting at Week 4 for every 4 weeks through IV infusion
TremelimumabDrug
Participants will receive single dose of 300 mg through IV infusion at Day 1
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Durvalumab; Drug: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measured: 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)
To assess the safety and tolerability of STRIDE in participants with advanced unresectable HCC
Measured: From screening until 90 days following discontinuation of the last dose of IMP [approx. up to 33 months]
Overall Survival (OS)
OS is defined as the time from the date of the first dose of IMP until death due to any cause.
Measured: From the date of the first dose of IMP until death [maximum follow-up approx. 33 months]
Progression-Free Survival (PFS)
PFS is defined as the time from the first dose of IMP until the date of objective PD (per RECIST 1.1 as assessed by the investigator) or death (by any cause in the absence of progression)
Measured: 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)
DCR-16w is defined as the percentage of participants who have a best objective response of complete response or partial response (by Week 16 + 7 days) or who have stable disease for at least 16 weeks (-7 days), following the start of study intervention as determined by the investigator per RECIST 1.1
Measured: At Week 16
Disease Control Rate at Week 24 (DCR-24w)
DCR-24w is defined as the percentage of participants who have a best objective response of complete response or partial response (by Week 24 + 7 days) or who have stable disease for at least 24 weeks (-7 days), following the start of study intervention per RECIST 1.1
Measured: At Week 24
Duration of Response (DOR)
DOR is defined as the time from the date of first documented response until the date of documented progression per RECIST 1.1, as assessed by the investigator or death in the absence of disease progression.
Measured: From the date of first documented response until the first date of documented progression or death in the absence of disease progression [approx. up to 33 months]
Duration of Treatment (DOT)
DOT is defined as time on study intervention.
Measured: From the date of first dose of IMP to the date of last dose of IMP [approx. up to 33 months]
Time to deterioration in Health-Related Quality of Life (HRQoL), assessed using the EORTC QLQ C-30.
Time to deterioration is defined as time from date of first dose of study intervention to the date of the first clinically meaningful deterioration (defined as a a decrease from baseline of at least 10 points for EORTC QLQ-C30 global HRQoL and functional scales, and an increase from baseline of at least 10 points for the EORTC QLQ-C30 symptom scales) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration. The domains/scales of the EORTC QLQ-C30 prioritized include global health status/QoL, functioning (physical), multi-term symptom (fatigue) and single item symptoms (appetite loss and nausea). Final scores range from 0 to 100, where higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales represent greater symptom severity.
Measured: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Clinically meaningful change from baseline in HRQoL as assessed by EORTC QLQ C-30
Clinically meaningful change from baseline in global health status/QoL, symptoms and function score (categorized as improvement, no change or deterioration) is defined as an absolute change in the score from baseline of ≥ 10 for scales from the EORTC QLQ-C30 to assess disease and treatment related symptoms and HRQoL.The domains/scales of the EORTC QLQ-C30 prioritized include global health status/QoL, functioning (physical), multi-term symptom (fatigue) and single item symptoms (appetite loss and nausea). Final scores range from 0 to 100, where higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales represent greater symptom severity.
Measured: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Best overall response for HRQoL as assessed by EORTC QLQ C-30
Best overall response for global health status/QoL, function and symptom (fatigue) will be derived as the best response the participant achieved, based on evaluable electronic patient-reported outcome (ePRO) data collected during the study period to assess disease and treatment related symptoms and HRQoL. The domains/scales of the EORTC QLQ-C30 prioritized include global health status/QoL, functioning(physical), multi-term symptom (fatigue) and single item symptoms (appetite loss and nausea). Final scores range from 0 to 100, where higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales represent greater symptom severity.
Measured: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Change from baseline in HRQoL as assessed by EORTC QLQ C-30
Change from baseline of global health status/QoL, symptom and functioning scores to assess disease and treatment related symptoms and HRQoL. The domains/scales of the EORTC QLQ-C30 prioritized include global health status/QoL, functioning(physical), multi-term symptom (fatigue) and single item symptoms(appetite loss and nausea). Final scores range from 0 to 100, where higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales represent greater symptom severity.
Measured: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Time to deterioration in HRQoL as assessed by EORTC QLQ-HCC18
Time to deterioration is defined as time from date of first dose of study intervention to the date of the first clinically meaningful deterioration (defined as an increase from baseline of at least 10 points for EORTC QLQ-HCC18) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration. The QLQ-HCC18 is an HCC-specific module from the EORTC comprising 18 questions to assess HCC symptoms. The module includes 6 multi-item domain scales and 2 single-item scales. Final scores range from 0 to 100 where higher scores indicate a greater level of symptom severity and a poorer HRQoL. The items prioritized are single items shoulder pain, abdominal pain and abdominal swelling.
Measured: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Clinically meaningful change from baseline in HRQoL as assessed by EORTC QLQ-HCC18
Clinically meaningful change from baseline (categorized as improvement, no change or deterioration) is defined as an absolute change in the score from baseline of ≥ 10 for scales/items from QLQ-HCC18 to assess disease-related symptoms. The single items prioritized are shoulder pain, abdominal pain and abdominal swelling. The EORTC QLQ-HCC18 module is an 18-item questionnaire. All questions have a 4-point scale: "Not at all," "A little," "Quite a bit," and "Very much." For each of the 8 domains (6 multiple-item scales and 2 single-item scales), final scores are transformed such that they range from 0 to 100, where higher scores indicate greater level of symptoms and worse symptom or a poorer HRQoL.
Measured: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Best overall response for HRQoL as assessed by EORTC QLQ-HCC18
Best overall response in single-item symptoms (shoulder pain, abdominal pain, abdominal swelling) will be derived as the best response the participant achieved, based on evaluable ePRO data collected during the study period to assess disease-related symptoms. The single items prioritized are shoulder pain, abdominal pain and abdominal swelling. The EORTC QLQ-HCC18 module is an 18-item questionnaire. All questions have a 4-point scale: "Not at all," "A little," "Quite a bit," and "Very much." For each of the 8 domains (6 multiple-item scales and 2 single-item scales), final scores are transformed such that they range from 0 to 100, where higher scores indicate greater level of symptoms and worse symptom or a poorer HRQoL.
Measured: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Change from baseline in HRQoL as assessed by EORTC QLQ-HCC18
Change from baseline assessment in EORTC QLQ-HCC18 scale/item score at each post baseline assessment. The prioritized single items scores are shoulder pain, abdominal pain and abdominal swelling. The EORTC QLQ-HCC18 module is an 18-item questionnaire. All questions have a 4-point scale: "Not at all," "A little," "Quite a bit," and "Very much." For each of the 8 domains (6 multiple-item scales and 2 single-item scales), final scores are transformed such that they range from 0 to 100, where higher scores indicate greater level of symptoms and worse symptom or a poorer HRQoL.
Measured: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2023
- Study start27 Jun 2023
- Primary completion30 Mar 2026
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Phase IIIb Non-randomised and non-blinded single arm study
- Masking
- None (open label)
- Enrolment
- 111 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephen Chan, MD, Principal investigator, Department of Clinical Oncology, Chinese University of Hong KongLorenza Rimassa, MD, Principal investigator, Humanitas Cancer Centre, IRCCS Humanitas Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05883644
- Sponsor's protocol ID
- D419CR00030
- Other IDs
- 2022-502012-37-00
- Acronym
- SIERRA
- Status last verified
- Sep 2026
- First submitted
- 22 May 2023
- Last updated
- 14 Sep 2026
- Results posted
- No
- 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 requests 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
Chan SL, Kudo M, Sangro B, Kelley RK, Kim JH, Pham B, Hong JY, Waldschmidt DT, Marino D, Gerolami R, Burgoyne AM, Masi G, Walsh RJ, Marquardt JU, Emeribe U, Balaji K, Sun P, Baur B, Rimassa L. First-line durvalumab and tremelimumab in poor-prognosis unresectable hepatocellular carcinoma: Phase IIIb single-arm SIERRA study. J Hepatol. 2026 Oct 6:S0168-8278(26)02919-3. doi: 10.1016/j.jhep.2026.10.002. Online ahead of print.
PubMed 42838226
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIIb Single Arm, Open-label, Multicentre Study of Durvalumab and Tremelimumab as First Line Treatment in Participants With Advanced Hepatocellular Carcinoma (SIERRA)
- ClinicalTrials.gov ID
- NCT05883644
- Acronym / sponsor ID
- SIERRA / D419CR00030
- Conditions
- Advanced Hepatocellular Carcinoma
- Keywords
- liver cancer, human mAb, immunoglobulin G1 kappa subclass, STRIDE, Barcelona Clinic Liver Cancer (BCLC), Child-Pugh
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 111 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 27 Jun 2023 (actual)
- Primary completion
- 30 Mar 2026 (actual)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 1 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase IIIb, open-label, single arm, multicentre study to assess the safety and efficacy of STRIDE as first-line therapy in participants with advanced unresectable HCC who have one of the following:
- Child-Pugh score B7 or B8 with a World Health Organisation Eastern Cooperative Oncology Group Performance Status (WHO/ECOG PS) of 0-1 at enrolment, or
- Child-Pugh class A with a WHO/ECOG PS of 2 at enrolment, or
- Child-Pugh class A with a WHO/ECOG PS of 0-1 and with evidence of chronic main trunk portal vein thrombosis at enrolment
Participants must not have received any prior systemic therapy for HCC. Participants may have previously received locoregional therapy (LRT) but must no longer be suitable for additional LRT. Any local treatment needs to have been completed at least 4 weeks prior to initiation of treatment. The study consists of 4 periods: screening (Day-28 to Day -1), Treatment period, safety follow-up and survival follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Phase IIIb Non-randomised and non-blinded single arm study
| Arm | Type | Receives |
|---|---|---|
| Durvalumab plus Tremelimumab | Experimental | Drug: Durvalumab, Drug: TremelimumabParticipants 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. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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.
Key exclusion criteria (23 listed)
- 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:
- Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAE] Grade > 1) caused by previous anticancer therapy
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 |
|---|---|---|
| DurvalumabParticipants will receive 1500 mg at Day 1 and later receive as monotherapy starting at Week 4 for every 4 weeks through IV infusion | Drug | Durvalumab plus Tremelimumab |
| TremelimumabParticipants will receive single dose of 300 mg through IV infusion at Day 1 | Drug | Durvalumab plus Tremelimumab |
Primary outcome
Incidence of grade 3 or 4 possibly related to treatment adverse events (PRAEs)
Time frame: From the date of first dose of IMP until 6 months after the initiation of study intervention
PRAE is defined as an AE which has been assessed by the investigator to be possibly related to IMP.
Objective response rate (ORR)
Time frame: From the first dose of IMP until progression, or the last evaluable assessment in the absence of progression [approx. up to 33 months]
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).
15 secondary outcomes
Number of participants with adverse events (AEs), serious adverse events (SAEs), adverse event of special interest (AESIs), immune-mediated AEs (imAEs)
Time frame: From screening until 90 days following discontinuation of the last dose of IMP [approx. up to 33 months]
Overall Survival (OS)
Time frame: From the date of the first dose of IMP until death [maximum follow-up approx. 33 months]
Progression-Free Survival (PFS)
Time frame: 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)
Time frame: At Week 16
Disease Control Rate at Week 24 (DCR-24w)
Time frame: At Week 24
Duration of Response (DOR)
Time frame: From the date of first documented response until the first date of documented progression or death in the absence of disease progression [approx. up to 33 months]
Duration of Treatment (DOT)
Time frame: From the date of first dose of IMP to the date of last dose of IMP [approx. up to 33 months]
Time to deterioration in Health-Related Quality of Life (HRQoL), assessed using the EORTC QLQ C-30.
Time frame: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Clinically meaningful change from baseline in HRQoL as assessed by EORTC QLQ C-30
Time frame: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Best overall response for HRQoL as assessed by EORTC QLQ C-30
Time frame: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Change from baseline in HRQoL as assessed by EORTC QLQ C-30
Time frame: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Time to deterioration in HRQoL as assessed by EORTC QLQ-HCC18
Time frame: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Clinically meaningful change from baseline in HRQoL as assessed by EORTC QLQ-HCC18
Time frame: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Best overall response for HRQoL as assessed by EORTC QLQ-HCC18
Time frame: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Change from baseline in HRQoL as assessed by EORTC QLQ-HCC18
Time frame: Every 8 weeks from date of first dose of IMP for the first 48 weeks and then every 12 weeks thereafter until treatment discontinuation and 90 days after last dose during safety follow-up [approx. up to 33 months]
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Derived from this study: PubMed 42838226Chan SL, Kudo M, Sangro B, Kelley RK, Kim JH, Pham B, Hong JY, Waldschmidt DT, Marino D, Gerolami R, Burgoyne AM, Masi G, Walsh RJ, Marquardt JU, Emeribe U, Balaji K, Sun P, Baur B, Rimassa L. First-line durvalumab and tremelimumab in poor-prognosis unresectable hepatocellular carcinoma: Phase IIIb single-arm SIERRA study. J Hepatol. 2026 Oct 6:S0168-8278(26)02919-3. doi: 10.1016/j.jhep.2026.10.002. Online ahead of print.
- 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 requests 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.
Stephen Chan, MD principal investigator
Department of Clinical Oncology, Chinese University of Hong Kong
Lorenza Rimassa, MD principal investigator
Humanitas Cancer Centre, IRCCS Humanitas Research Hospital
40 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Durvalumab and Tremelimumab in people with Advanced Hepatocellular Carcinoma, run by AstraZeneca at 40 sites in 10 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 17 inclusion and 23 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 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in Italy, Japan, France, South Korea, Spain and 5 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Incidence of grade 3 or 4 possibly related to treatment adverse events (PRAEs) (time frame: From the date of first dose of IMP until 6 months after the initiation of study intervention). The study lists 2 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 NCT05883644, 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 14 Sep 2026.