Hepatocellular CarcinomaPhase 2TREMENDOUS-2NCT07081633
Durvalumab and Tremelimumab With Lenvatinib as First-line Treatment in Patients With Unresectable Hepatocellular Carcinoma
A Phase 2 study testing Durvalumab, Tremelimumab and Lenvatinib in people with Hepatocellular Carcinoma, run by AstraZeneca at 23 sites in 2 countries.
Trial summary
This is a Phase II, single-arm, multicentre study, assessing the efficacy and safety of durvalumab and tremelimumab with lenvatinib in participants with unresectable HCC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Durvalumab, Tremelimumab and Lenvatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 114 participants
- Where
- 23 sitesin 2 countries
- Study dates
- 5 Aug 2025to 31 Dec 2028
- Phase
- Phase 2
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed HCC based on histopathological findings from tumor tissues or radiologically findings.
- Must not have received prior systemic therapy for unresectable HCC.
- Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C.
- Child-Pugh Score class A.
- ECOG performance status of 0 or 1 at enrollment.
- At least 1 measurable lesion per RECSIT 1.1 guidelines
Who cannot join
- Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Grade ≥2 from previous anticancer therapy.
- History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy.
- Clinically meaningful ascites.
- Patients with main portal vein thrombosis.
- Active or prior documented GI bleeding.
- Patient currently exhibits symptomatic or uncontrolled hypertension.
- Patients co-infected with HBV and HCV, or co-infected with HBV and hepatitis D virus (HDV)
- Uncontrolled intercurrent illness
Trial locations and contacts
23 sites in 2 countries.
23 sites in 2 countries
China22 sites
Research Site
Beijing, 100029
Research Site
Beijing, 100044
Research Site
Beijing, 100142
Research Site
Chengdu, 610078
Research Site
Chongqing, 400016
Research Site
Guangzhou, 510060
Research Site
Guangzhou, 510095
Research Site
Guangzhou, 510120
Research Site
Guangzhou, 510515
Research Site
Hangzhou, 310022
Research Site
Hefei, 230022
Research Site
Jinan, 250021
Research Site
Nanjing, 210009
Research Site
Nanjing, 210029
Research Site
Ningbo, 315010
Research Site
Shanghai, 200032
Research Site
Shanghai, 200438
Research Site
Tianjin, 300060
Research Site
Wenzhou, 325000
Research Site
Wuhan, 430030
Research Site
Xiamen, 361004
Research Site
Zhengzhou, 450052
About this study
Official title: An Open-label, Multi-center Phase II Study of Durvalumab and Tremelimumab With Lenvatinib as First-line Treatment in Patients With Unresectable Hepatocellular Carcinoma
This is a Phase II, single-arm, multicentre study, assessing the efficacy and safety of durvalumab and tremelimumab with lenvatinib in participants with unresectable HCC.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Durvalumab, Tremelimumab, Lenvatinib
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736
Durvalumab IV (intravenous infusion)
TremelimumabDrug
Tremelimumab IV (intravenous infusion)
LenvatinibCombination product
Lenvatinib Oral
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Durvalumab and Tremelimumab with Lenvatinib Receives: Drug: Durvalumab; Drug: Tremelimumab; Combination Product: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS) per RECIST 1.1
Efficacy endpoint
Measured: From the date of first dose until the date of objective PD per RECIST 1.1 or death, whichever came first. It will be assessed when approximately 69 PFS events have occurred (60% maturity), approximately 8 months after the last patients dosed.
Secondary outcomes (6)
Grade ≥ 3 TRAE within 6 months after the initiation of study intervention
safety endpoint
Measured: From first dose to 6 months after the initiation of study intervention
Overall Survival (OS)
Efficacy endpoint
Measured: From the date of the first dose of study intervention until death due to any cause. It will be assessed when approximately 69 OS events have occurred (60% maturity), approximately 24 months after last participant has been assigned to study intervention.
Objective Response Rate (ORR) per RECIST 1.1
Efficacy endpoint
Measured: From the date of the first dose of study intervention until the date of objective PD per RECIST 1.1. It is anticipated that this analysis will be performed approximately 8 months after the last patient has been assigned to study intervention.
Disease Control Rate (DCR) per RECIST 1.1
Efficacy endpoint
Measured: From the date of the first dose of study intervention until the date of objective PD per RECIST 1.1. It is anticipated that this analysis will be performed approximately 8 months after the last patient has been assigned to study intervention.
Duration of response (DoR) per RECIST 1.1
Efficacy endpoint
Measured: From the date of response until the date of objective PD per RECIST 1.1 or death, whichever came first. It is anticipated that this analysis will be performed approximately 8 months after the last patient dosed.
Progression Free Survival (PFS) per mRECIST
Efficacy endpoint
Measured: From the date of the first dose until the date of objective PD per mRECIST or death, whichever came first. It will be assessed when approximately 69 PFS events have occurred (60% maturity), approximately 8 months after the last patients dosed.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2025
- Study start5 Aug 2025
- Primary completion30 Nov 2026 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07081633
- Sponsor's protocol ID
- D419CL00025
- Acronym
- TREMENDOUS-2
- Status last verified
- Oct 2026
- First submitted
- 23 Jun 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- 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. Plan Description: All request will be evaluated as per the Az disclosure commitment: https://astrazenecaarouptrials.pharmacm.com/ST/Submission/Disclosure Yes. indicates that Az are accepting requests for IPD ,but this does not mean are quests will be shared