Study of Durvalumab Plus Tremelimumab as First-line Treatment in Chinese Patients With Unresectable Hepatocellular Carinoma

Study Overview
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Brief Summary
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This is a prospective, open label, multi-center, interventional study to assess the safety and efficacy of Druvalumab plus Tremelimumab as first-line treatment in Chinese patients with unresectable hepatocellular carcinoma.

Official Title
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An Open-label, Multi-center Phase IIIb Study of Durvalumab and Tremelimumab as First-Line Treatment in Patients With Unresectable Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Durvalumab
* Drug: Tremelimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed HCC based on histopathological findings from tumor tissue or radiologically findings No prior systemic therapy for HCC Barcelona Clinic Liver Cancer (BCLC) stage B (not eligible for locoregional therapy) or stage C Child-Pugh Score class A or B ECOG performance status (PS) of 0-2 at enrollment (Child-Pugh Score class A and ECOG PS of 0-1 will be enrolled in cohort 1 and Child-Pugh Score class B or ECOG PS of 2 will be enrolled in cohort 2) At least 1 measurable lesion per RECSIT 1.1 guidelines 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 6 months HBV and HVC co-infection, or HBV and Hep D co-infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cohort 1<br>durvalumab in combination with tremelimumab | Drug: Durvalumab<br>* Durvalumab IV (intravenous infusion)<br>* Other names: MEDI4736;Drug: Tremelimumab<br>* Tremelimumab IV (intravenous infusion)<br>|
| Experimental: cohort 2<br>durvalumab in combination with tremelimumab | Drug: Durvalumab<br>* Durvalumab IV (intravenous infusion)<br>* Other names: MEDI4736;Drug: Tremelimumab<br>* Tremelimumab IV (intravenous infusion)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ≥Grade 3 Adverse Events and Adverse Events of Special Interest of Cohort 1 |  | From the time of signature of informed consent, throughout the treatment period, and up to the follow-up period, assessed up to 29 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ≥Grade 3 Adverse Events and Adverse Events of Special Interest of Cohort 2 |  | From the time of signature of informed consent, throughout the treatment period, and up to the follow-up period, assessed up to 29 months | 
| Overall Survival (OS) |  | From the first dose of treatment to the date of death, regardless of the actual cause of the subject's death, assessed up to 29 months | 
| Progression Free Survival (PFS) per RECIST v1.1/mRECIST |  | From first dose of treatment until progression per RECIST 1.1/ mRECIST as assessed by the Investigator or death due to any cause prior to progression, assessed up to 15 months | 
| Objective Response Rate (ORR) per RECIST 1.1/ mRECIST |  | Until progression, assessed up to 15 months | 
| Disease Control Rate (DCR) per RECIST 1.1/ mRECIST |  | Until progression, assessed up to 15 months | 
| Rate of Adverse Events |  | From the time of signature of informed consent, throughout the treatment period, and up to the follow-up period, assessed up to 29 months | 
| Duration of response (DoR) per RECIST 1.1/mRECIST |  | From the first dose, until progression, assessed up to 15 months |