NCT03298451 · CITED IN SOURCE DOCUMENTS

Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-07-27

This is a randomized, open-label, multi-center, global, Phase III study to assess the efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for unresectable HCC. The patients cannot be eligible for locoregional therapy

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival (OS) - Treme 300 mg x1 Dose + Durva 1500 mg vs Sora 400 mg

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outcome · POSTED

Overall Survival (OS) - Durva 1500 mg vs Sora 400 mg

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outcome · POSTED

Overall Survival (OS) at 18, 24, and 36 Months After Randomization

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outcome · POSTED

Progression Free Survival (PFS)

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outcome · POSTED

Time To Progression (TTP)

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outcome · POSTED

Objective Response Rate (ORR)

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outcome · POSTED

Disease Control Rate (DCR)

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outcome · POSTED

Duration of Objective Response (DoR)

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outcome · POSTED

Overall Survival (OS) by PD-L1

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outcome · POSTED

EORTC QLQ-C30 Time to Global Health Status/QoL Deterioration

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outcome · POSTED

EORTC QLQ-HCC18 Time to Symptom (Abdominal Pain) Deterioration

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outcome · POSTED

EORTC QLQ-HCC18 Time to Symptom (Shoulder Pain) Deterioration

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outcome · POSTED

EORTC QLQ-HCC18 Time to Symptom (Abdominal Swelling) Deterioration

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outcome · POSTED

Presence of ADA for Durvalumab

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outcome · POSTED

Presence of ADA for Tremelimumab

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outcome · POSTED

Summary of Durvalumab Concentration Over Time

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outcome · POSTED

Summary of Tremelimumab Concentration Over Time

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion criteria * HCC based on histopathological confirmation * No prior systemic therapy for 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 Exclusion criteria * Hepatic encephalopathy within past 12 months or requirement for medication to prevent or control encephalopathy * Clinically meaningful ascites * Main portal vein tumor thrombosis * Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within 12 months * HBV and HVC co-infection, or HBV and Hep D co-infection
healthy Volunteers: false
maximum Age: 100 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Durvalumab
intervention Names
Drug: Durvalumab
label
Arm 1
type
EXPERIMENTAL
description
Durvalumab in combination with tremelimumab (Regimen 1)
intervention Names
Drug: Tremelimumab (Regimen 1)
Drug: Durvalumab (Regimen 1)
label
Arm 2
type
EXPERIMENTAL
description
Durvalumab in combination with tremelimumab (Regimen 2)
intervention Names
Drug: Tremelimumab (Regimen 2)
Drug: Durvalumab (Regimen 2)
label
Arm 3
type
EXPERIMENTAL
description
Sorafenib
intervention Names
Drug: Sorafenib
label
Arm 4
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Arm 1
description
Durvalumab IV (intravenous infusion).
name
Durvalumab
other Names
MEDI4736
type
DRUG
arm Group Labels
Arm 2
description
Tremelimumab IV (intravenous infusion).
name
Tremelimumab (Regimen 1)
type
DRUG
arm Group Labels
Arm 3
description
Tremelimumab IV (intravenous infusion).
name
Tremelimumab (Regimen 2)
type
DRUG
arm Group Labels
Arm 4
description
Sorafenib, as per standard of care
name
Sorafenib
type
DRUG
arm Group Labels
Arm 2
description
Durvalumab IV (intravenous infusion).
name
Durvalumab (Regimen 1)
type
DRUG
arm Group Labels
Arm 3
description
Durvalumab IV (intravenous infusion).
name
Durvalumab (Regimen 2)
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 1324
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This primary outcome measure presents OS analysis of Treme 300mg x1 dose + Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021).
measure
Overall Survival (OS) - Treme 300 mg x1 Dose + Durva 1500 mg vs Sora 400 mg
time Frame
From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).

secondary Outcomes

description
OS was defined as the time from the date of randomization until death due to any cause, regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Any participant not known to have died at the DCO date was censored based on the last recorded date on which the participant was known to be alive. If the last known date alive or if the date of death was after the DCO date, participants were censored at the DCO date. This secondary outcome measure presents OS analysis of Durva 1500 mg vs Sora 400 mg at the time of the final analysis DCO (27Aug2021).
measure
Overall Survival (OS) - Durva 1500 mg vs Sora 400 mg
time Frame
From the date of randomization until death due to any cause, assessed up to the data cut-off date (27Aug2021, to a maximum of approximately 46 months).
description
Percentage of participants who were alive at fixed time points (18, 24, and 36 months) after randomization. The estimated percentage of survival along with the 95% confidence interval were calculated using Kaplan-Meier technique on the full analysis set.
measure
Overall Survival (OS) at 18, 24, and 36 Months After Randomization
time Frame
At 18, 24, and 36 months post-randomization. Assessed at the final analysis DCO (27Aug2021).
description
PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 \[RECIST 1.1\] using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death by any cause in the absence of progression, regardless of whether the patient withdrew from study treatment or received another anticancer therapy prior to progression. Progression (i.e., PD) was defined as a at least 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir.
measure
Progression Free Survival (PFS)
time Frame
Tumor scans performed at baseline, every 8 weeks for the first 48 weeks following randomization, and every 12 weeks thereafter until RECIST 1.1-defined progression. Assessed up to DCO (27Aug2021, to a maximum of approximately 46 months)
description
TTP was defined as the time from randomization until objective tumor progression in the absence of death. If participants died without tumor progression, they were censored at the time of death.
measure
Time To Progression (TTP)
time Frame
From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
description
ORR (per RECIST 1.1 as assessed by the Investigator) was defined as the number (%) of participants with at least 1 confirmed visit response of CR or PR until progression, or the last evaluable assessment in the absence of progression. Participants who go off treatment without progression, receive a subsequent therapy, and then respond will not be included as responders in the ORR. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.
measure
Objective Response Rate (ORR)
time Frame
From the date of randomization until objective tumor progression, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
description
Number (%) of participants with a Best Objective Response (BoR) of CR, PR, or SD. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters. Stable disease (ie., SD) was defined as neither sufficient decrease in sum of diameters to qualify for PR nor sufficient increase to qualify for progression.
measure
Disease Control Rate (DCR)
time Frame
From the date of randomization until objective tumor progression or date of death, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
description
Time from the date of first documented confirmed response (complete or partial response) until the first date of documented progression or death in the absence of disease progression. Complete response (ie., CR) was defined as disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm. Partial response (ie., PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters.
measure
Duration of Objective Response (DoR)
time Frame
From the date of first documented response until the first date of documented progression or death, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
description
Overall survival by baseline PD-L1 expression levels (positive vs. negative). PD-L1 expression level is based on the Tumor and Immune Cell Positivity (TIP) score method as: PD-L1 Positive (TIP ≥ 1%) or PD-L1 Negative (TIP \< 1%).
measure
Overall Survival (OS) by PD-L1
time Frame
From the date of randomization until death due to any cause, assessed until the final analysis DCO (27Aug2021, to a maximum of approximately 46 months).
description
European Organisation for Research and Treatment of Cancer (EORTC) 30-item core quality of life questionnaire (QLQ-C30), which consists of 30 questions combined to produce a global health status/QoL scale. Higher scores indicate better health. A clinically meaningful deterioration is defined as a decrease in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.
measure
EORTC QLQ-C30 Time to Global Health Status/QoL Deterioration
time Frame
At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.
description
EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.
measure
EORTC QLQ-HCC18 Time to Symptom (Abdominal Pain) Deterioration
time Frame
At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.
description
EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.
measure
EORTC QLQ-HCC18 Time to Symptom (Shoulder Pain) Deterioration
time Frame
At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.
description
EORTC 18-item hepatocellular cancer health-related quality of life questionnaire (QLQ-HCC18) is an 18-item questionnaire design used along with the 30-item EORTC QLQ-C30, which includes 8 symptom scales such as fatigue, jaundice, body image, nutrition, pain, fever, sex life and abdominal swelling. A high score for a symptom scale/item represents a high level of symptomatology/problem. A clinically meaningful deterioration is defined as an increase in the score from baseline of ≥10. Time to deterioration is defined as the time from the date of randomization until the date of the first clinically meaningful deterioration that is confirmed at a subsequent visit or death by any cause in the absence of a clinically meaningful deterioration, regardless of whether the patient discontinues study drug(s) or receives another anticancer therapy.
measure
EORTC QLQ-HCC18 Time to Symptom (Abdominal Swelling) Deterioration
time Frame
At baseline and every 8 weeks for the first 48 weeks and then every 12 weeks thereafter until death or the final analysis DCO (27Aug2021), assessed up to approximately 46 months.

Full study description

brief Summary: This is a randomized, open-label, multi-center, global, Phase III study to assess the efficacy and safety of durvalumab plus tremelimumab combination therapy and durvalumab monotherapy versus sorafenib in the treatment of patients with no prior systemic therapy for unresectable HCC. The patients cannot be eligible for locoregional therapy
detailed Description: The study population includes patients 18 years of age or older with advanced HCC, Barcelona Clinic Liver Cancer stage B not eligible for locoregional therapy or stage C, and Child-Pugh A classification liver disease. Patients must not have received any prior systemic therapy for unresectable HCC. Patients in all treatment arms may continue receiving their originally assigned treatment, at the Investigator's discretion, until progression Patients in all arms with confirmed PD who, in the Investigator's opinion, continue to receive benefit from their assigned treatment and meet the criteria for treatment in the setting of PD may continue to receive their assigned treatment. If a patient discontinues study drug(s) due to disease progression, the patient will enter survival follow-up. Patients who have discontinued treatment due to toxicity or symptomatic deterioration or who have commenced subsequent anticancer therapy, will have tumor assessments until confirmed PD and will be followed for survival

Source references

references

citation
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