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Sequential therapy of Regorafenib combined with one kind of ICIs after standard HAIC treatment in advanced hepatocellular carcinoma (HCC).

ICIs: atezolizumab, pembrolizumab, nivolumab, camrelizumab, tislelizumab, sintilimab or other ICIs.

Regorafenib: 80mg/day, PO, QD, d1～d21, Q4W ICIs: 200mg/day, IV, d1,Q3W

Regorafenib combine with ICIs

Ming Zhao, M.D. & Ph.D.

Ning Lyu, M.D.

Ming Zhao, MD

Ming Zhao, PHD

Hepatic artery infusion chemotherapy (HAIC) has shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC). Some patients can be converted to loco-regional therapies after 4-6 cycles of HAIC treatment. But most of these patients still need to concern the sequential treatment after standard HAIC treatment (4-6 cycles). Combination of anti-angiogenic molecular targeted therapy and immune checkpoint inhibitor (ICI) therapy has shown promising antitumor activity in HCC. Regorafenib is one of the standard second-line systemic therapy for advanced HCC. In this study, we will evaluate the efficacy and safety of sequential therapies of Regorafenib plus ICI in patients with advanced HCC who have completed 4-6 cycles of HAIC.

The standard procedure for HAIC is that femoral artery puncture and catheterization are performed in every cycle of treatment, a micro-catheter is inserted and located in feeding hepatic artery. The therapeutic scheme is modified FOLFOX6 regimens including oxaliplatin, leucovorin and Fluorouracil. All chemo-drugs are given by HAI. A total of 4-6 cycles of HAIC are performed and the treated efficacy is evaluated. Patient who is not suitable for loco-regional therapies after 4-6cycles of HAIC becomes to the candidate of sequential therapies of regorafenib plus ICIs. The regorafenib 80 mg/day was uses in sequential treatment. And ICIs were used intravenously at the standard dose. Patients received sequential treatment will begin no earlier than 30 days following the last HAIC procedure.

Observation Study of Sequential Regorafenib Plus ICIs After HAIC for Advanced Hepatocellular Carcinoma

Observation Study of Sequential Regorafenib Combined With Immunocheckpoint Inhibitors After Hepatic Artery Infusion Chemotherapy for Advanced Hepatocellular Carcinoma

Absence of disease progression other than death

Absence of regrowth inside the treated lesion

Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0

Tumor response to Regorafenib Combined With ICIs according to RECIST 1.1

Sun Yat-sen University

Professor

Micronutrients

Hematinics

Vitamins

Immune Checkpoint Inhibitors

Leucovorin

Fluorouracil

Angiogenesis Inhibitors

Oxaliplatin

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

Each patient received an artery catheter procedure guided by digital subtraction angiography.

digital subtraction angiography.

Hepatic artery infusion chemotherapy. The FOLFOX (oxaliplatin 130 mg/m2, leucovorin 200 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2,400 mg/m2) regimen was sequentially infused through the catheter every cycle (3 weeks).

FOLFOX (oxaliplatin , leucovorin , fluorouracil , and fluorouracil )

Immune checkpoint inhibitors (ICIs) plus antiangiogenic agents can achieve better efficacy than sorafenib in the treatment of hepatocellular carcinoma (HCC) within a certain period of time, but more than half of the patients are still insensitive to the treatment. There is no evidence-based basis for second-line treatment after the progression of the disease.In view of the effectiveness of Hepatic arterial infusion (HAIC) in the first-line treatment of HCC in the Chinese population, this study intends to launch a prospective intervention study to explore the efficacy and safety of HAIC treatment in patients with advanced HCC after the failure of ICIs and antiangiogenic agents combination therapy, and to provide high-level evidence for optimizing the second-line treatment of advanced HCC in the future.

Each patient received an artery catheter procedure guided by digital subtraction angiography. Then, the FOLFOX (oxaliplatin 130 mg/m\^2, leucovorin 200 mg/m\^2, fluorouracil 400 mg/m\^2, and fluorouracil 2,400 mg/m\^2) regimen was sequentially infused through the catheter every cycle (3 weeks).A maximum of 4-6 courses of continuous hepatic artery infusion chemotherapy were received.If the patient has extrahepatic metastasis at baseline, ICIs should be used as a systemic treatment according to the severity of the disease. The drug type and treatment protocol of ICIs should be based on the most advanced treatment progress in the world.

A Study of the Application of HAIC in Advanced HCC Previously Treated With ICIs and Antiangiogenic Agents

A Study of the Application of Hepatic Arterial Infusion in Advanced Hepatocellular Carcinoma Previously Treated With Immune Checkpoint Inhibitors and Antiangiogenic Agents

Tumor response to HAIC according to RECIST 1.1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Observation Study of Sequential Regorafenib Plus ICIs After HAIC for Advanced Hepatocellular Carcinoma	NCT05573282	Hepatocellular ...	Regorafenib com...	18 Years - 75 Years	Sun Yat-sen University
A Study of the Application of HAIC in Advanced HCC Previously Treated With ICIs and Antiangiogenic Agents	NCT05718492	Hepatocellular ...	digital subtrac... FOLFOX (oxalipl...	18 Years - 75 Years	Sun Yat-sen University

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