Anlotinib Hydrochloride Capsules Combined With Penpulimab Injection for the Treatment of Hepatocellular Carcinoma at High Risk of Recurrence.

Study Overview
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Brief Summary
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The primary objective of this study was to evaluate the efficacy of anlotinib hydrochloride capsules combined with penpulimab injection (test group) versus placebo (control group) for adjuvant therapy after radical surgery or ablation in HCC patients with high risk of recurrence by assessing recurrence-free survival (RFS).

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multicenter Phase 3 Study of Anlotinib Hydrochloride Capsules Combined With Penpulimab Injection in Patients With High Risk of Relapse After Radical Surgery or Ablation of Hepatocellular Carcinoma (HCC).

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Anlotinib hydrochloride capsules, Penpulimab injection
* Drug: Anlotinib hydrochloride capsules -matching placebo, Penpulimab injection -matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-75 years old; Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1; Predicted survival ≥12 weeks. Subjects with hepatocellular carcinoma (HCC) confirmed by histopathology or cytology or who meet the diagnostic criteria for Primary Liver Cancer 2022 or the American Association for the Study of Hepatology (AASLD) hepatocellular carcinoma. Subjects who received radical excision or ablation (Radio Frequency Ablation (RFA) or Microwave Ablation (MWA) only) within 4 to 12 weeks prior to randomization (multiple modalities or combined or multiple treatments are not acceptable). No major vena portae 3 (Vp3) or vena portae 4 (Vp4) in the portal vein or any level of vascular invasion in the hepatic vein or inferior vena cava. No extrahepatic metastasis. High risk factors for recurrence after radical resection or complete ablation. Complete recovery from surgical resection or ablation within 4 weeks before randomization. Exclusion Criteria: Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC histology. Evidence of residual, recurrent, or metastatic disease at randomization. More than one surgical treatment for hepatocellular carcinoma; Received more than 1 prophylactic Transcatheter Arterial Chemoembolization (TACE) treatment after surgery; or received Hepatic Artery Infusion Chemotherapy (HAIC) therapy after surgery. Previous use of antiangiogenic drugs or PD-1, Programmed Cell Death-Ligand 1 (PD-L1) and other related immunotherapy drugs or systemic chemotherapy drugs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anlotinib hydrochloride capsules + Penpulimab injection<br>Anlotinib hydrochloride capsules + Penpulimab injection, 21 days as a treatment cycle. | Drug: Anlotinib hydrochloride capsules, Penpulimab injection<br>* Anlotinib hydrochloride capsules is a multitargeted receptor tyrosine kinase inhibitor. Penpulimab injection is a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1).<br>|
| Placebo Comparator: Anlotinib hydrochloride capsules -matching placebo+ Penpulimab injection -matching placebo<br>Anlotinib hydrochloride capsules -matching placebo+ penpulimab injection -matching placebo, 21 days as a treatment cycle. | Drug: Anlotinib hydrochloride capsules -matching placebo, Penpulimab injection -matching placebo<br>* placebo control, no active substance.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-free survival (RFS) | RFS assessed by the Blinded Independent Image Review Committee and the investigator is the time from randomization to the first local, regional recurrence or distant metastasis, or death from any cause, whichever occurred first. | Baseline up to 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recurrence(TTR) | TTR assessed by the Blinded Independent Image Review Committee and the investigator is the time from randomization to the first local, regional recurrence or distant metastasis, whichever occurred first. | Baseline up to 3 years. | 
| Time to extrahepatic metastasis or macrovascular invasion | Time to extrahepatic metastasis or macrovascular invasion as assessed by the investigator. | Baseline up to 3 years. | 
| Overall survival (OS) | OS defined as the time from the date of randomization until the date of death due to any cause. | Baseline up to 3 years. | 
| Objective response rate (ORR) after first recurrence | subjects with evaluable tumor lesion status who were cross-treated with Anlotinib hydrochloride capsules combined with Penpulimab injection developed complete response or partial response after a first HCC relapse as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. | Baseline up to 3 years. |