Sintilimab Combined With Lenvatinib in Local Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This ia a single-arm, single-center, not-randomized, open-label phase II study. The purpose of this study is to evaluate the efficacy and safety of Sintilimab (PD-1 antibody) combined with Lenvatinib(TKI) for the treatment of local advanced hepatocellular carcinoma.

Official Title
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Sintilimab Combined With Lenvatinib in Local Advanced Hepatocellular Carcinoma: A Single-arm, Open-label, Phase II Clinical Study

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: Sintilimab
* Drug: Lenvatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a diagnosis of hepatocellular carcinoma confirmed by radiology, histology, or cytology Barcelona Clinic Liver Cancer (BCLC) Stage C disease without any distant or lymphatic metastasis , or BCLC Stage B disease not amenable to curative surgery No previous systemic anticancer treatment or TACE treatment Age ≥18 years ECOG performance status: 0-1 Child Pugh score≤7 Has at least one measurable hepatocellular carcinoma (HCC) lesion based on RECIST 1.1 Life expectancy ≥12 weeks. Patients must be able to understand and willing to sign a written informed consent document Exclusion Criteria: Fibrous lamina hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma History of hepatic encephalopathy or liver transplantation Pleural effusion, ascites and pericardial effusion with clinical symptoms or needing drainage. Untreated hepatitis infection: HBV DNA>2000IU/mlor10000 copy/ml, HCV RNA> 1000copy/ml, both HbsAg and anti-HCV body are positive. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. History of symptomatic interstitial lung disease or other conditions that may cause confusion when discovering or managing suspicious drug-related lung toxicity With serious systemic diseases such as heart disease and cerebrovascular disease, and the condition is unstable or uncontrollable. Evidence of active pulmonary tuberculosis (TB). Positive test of immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) History of allergic reactions to related drugs Pregnant women, nursing mothers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sintilimab Plus Lenvatinib<br>Participants receive lenvatinib 12 mg (for participants with screening body weight ≥60 kg) or 8 mg (for participants with screening body weight <60 kg) orally once a day (QD) plus sintilimab 200 mg intravenously every 3 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. | Biological: Sintilimab<br>* 200mg intravenously every 3 weeks<br>* Other names: IBI308;Drug: Lenvatinib<br>* 12 mg (or 8 mg) once daily (QD) oral dosing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) |  | 1 year after the last patient's enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 2 years after the last patient's enrollment | 
| Safety of combination sintilimab and lenvatinib as evaluated by incidence of adverse events(AEs), serious adverse events (SAEs). |  | 2 years after the last patient's enrollment | 
| Conversion rate to surgery | Conversion rate defined as the proportion of participants be able to receive surgery after the initiation of the study treatment | 1 year after the last patient's enrollment | 
| Tumor mutation burden in association with ORR and survival. | It will be performed by NGS. | 1 year after the last patient's enrollment |