Regorafenib Plus Tislelizumab as First-line Systemic Therapy for Patients With Advanced Hepatocellular Carcinoma

2019-12-06 00:24:52 | BioPortfolio


Combination of anti-angiogenic molecular targeted therapy and anti- programmed cell death -1 immune checkpoint inhibitor (ICI) therapy has shown promising antitumor activity in multiple cancer types, including patients with advanced hepatocellular carcinoma (HCC). The safety profile and optimal dosage of targeted therapy should be carefully evaluated by clinical trials. Regorafenib is one of the standard second-line systemic therapy for advanced HCC. The present study will test the safety and efficacy of combination of regorafenib and tislelizumab, an anti-programmed cell death-1 ICI. The investigator(s) thus hypothesized that combination of tislelizumab and regorafenib is a tolerable regimen and may improve treatment efficacy for patients with advanced HCC. The present study will explore safety and efficacy of the combination of tislelizumab plus regorafenib as first-line therapy for advanced HCC.


Combination of ICI with anti-angiogenic therapy has been most extensively studies in patients with renal cell carcinoma, for whom both ICI and anti-angiogenic therapy have proven anticancer activity as single-agent therapy. Objective response rate of 30-60% was observed, far exceeding the response rate of single-agent therapy (around 20%). Results from several early-phase trials of this type of combination also support the potential anti-tumor synergy between ICI and anti-angiogenic therapy (multi-kinase inhibitors or monoclonal antibody targeting the vascular endothelial growth factor signaling pathway) in advanced HCC. Further studies should focus on identifying the optimal targeted agent and its biologically effective dosage to achieve the best therapeutic window for the treatment of HCC.

Current evidence indicated the following:

1. Combination of ICI and anti-angiogenic therapy in advanced HCC may have better anti-tumor efficacy compared with single-agent therapy;

2. The immune modulatory effects of the multi-kinase inhibitors may be achieved at dosage lower than recommended for single-agent therapy in the clinic; using this lower dosage when combined with ICI may lower the treatment-related adverse events.

3. Objective response of 40% to 50% was recently reported in a phase 1 study of regorafenib plus nivolumab for patients with advanced gastric or colorectal cancer was reported recently (Fukuoka S, et al. American Society Of Clinical Oncology 2019, abstract#2522). Grade 3 or greater treatment-related adverse events were found in 27% of subjects who received regorafenib 80 mg per day and in 44% of patients who received regorafenib 120 mg per day. Therefore, regorafenib 80 mg/day was defined as the optimal dosage in combination with nivolumab.

Study Design


Advanced Hepatocellular Carcinoma


Tislelizumab+regorafenib for part 1;Tislelizumab+regorafenib for group 1 of part 2; Placebo+regorafenib for group 2 of part 2.


Not yet recruiting


National Taiwan University Hospital

Results (where available)

View Results


Published on BioPortfolio: 2019-12-06T00:24:52-0500

Clinical Trials [3662 Associated Clinical Trials listed on BioPortfolio]

A Study to Investigate Sitravatinib as Monotherapy and in Combination With Tislelizumab in Patients With Unresectable Locally Advanced or Metastatic HCC or GC/GEJC

The purpose of this study is to evaluate the safety,tolerability, pharmacokinetics and preliminary antitumor activity of sitravatinib as monotherapy and in combination with tislelizumab in...

Regorafenib Eye Drops: Investigation of Efficacy and Safety in Neovascular Age Related Macular Degeneration

Part A (Phase IIa): Primary objectives: The study part A is designed to investigate whether the use of regorafenib eye drops can help patients with neovascular (wet) Age-Related Ma...

The Safety and Efficacy Study of Regorafenib (CT) Compared With Regorafenib (STIVARGA) in Patients With Solid Tumors

This is a multinational, double-blind, randomized, parallel-group Phase 2 clinical trial evaluating the efficacy of Regorafenib (CT).and Regorafenib (STIVARGA)

Study of Tislelizumab and/or Pamiparib Containing Treatments in Patients With Advanced Malignancies

This is an open-label, multicenter, extension study to evaluate the long-term safety of tislelizumab or pamiparib given either as monotherapy or in combination with each other or with othe...

Efficacy of Ginseng for Patients on Regorafenib

This is a randomized, multi-center phase II study of ginseng in colorectal cancer patients treated with regorafenib to determine if ginseng will reduce fatigue in this patient population a...

PubMed Articles [13422 Associated PubMed Articles listed on BioPortfolio]

A comparison of regorafenib and fruquintinib for metastatic colorectal cancer: a systematic review and network meta-analysis.

The optimal treatment in the third-line and later-line setting for metastatic colorectal cancer (mCRC) has not been established. As reported, regorafenib and fruquintinib have shown to be superior to ...

Safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice in the prospective, observational CORRELATE study.

Regorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regoraf...

Bilateral sensorineural hearing loss induced by regorafenib.

Regorafenib is a novel multi-targeted tyrosine kinase inhibitor approved for use in refractory metastatic colorectal cancer, advanced gastrointestinal stromal tumours and hepatocellular carcinoma. We ...

Preliminary experience on safety of regorafenib after sorafenib failure in recurrent hepatocellular carcinoma after liver transplantation.

Regorafenib is one option for second-line treatment of hepatocellular carcinoma (HCC), improving overall survival (OS) of sorafenib-tolerant patients who develop progression. We aim to evaluate safety...

Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan.

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety an...

Medical and Biotech [MESH] Definitions

Cysts of one of the parts of the mediastinum: the superior part, containing the trachea, esophagus, thoracic duct and thymus organs; the inferior middle part, containing the pericardium; the inferior anterior part containing some lymph nodes; and the inferior posterior part, containing the thoracic duct and esophagus.

The great peninsula of southwest Asia comprising most of the present countries of the Middle East. It has been known since the first millennium B.C. In early times it was divided into Arabia Petraea, the northwest part, the only part ever conquered, becoming a Roman province; Arabia Deserta, the northern part between Syria and Mesopotamia; and Arabia Felix, the main part of the peninsula but by some geographers restricted to modern Yemen. (From Webster's New Geographical Dictionary, 1988, p63)

Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia.

A large vessel supplying the whole length of the small intestine except the superior part of the duodenum. It also supplies the cecum and the ascending part of the colon and about half the transverse part of the colon. It arises from the anterior surface of the aorta below the celiac artery at the level of the first lumbar vertebra.

Either of a pair of compound bones forming the lateral (left and right) surfaces and base of the skull which contains the organs of hearing. It is a large bone formed by the fusion of parts: the squamous (the flattened anterior-superior part), the tympanic (the curved anterior-inferior part), the mastoid (the irregular posterior portion), and the petrous (the part at the base of the skull).

More From BioPortfolio on "Regorafenib Plus Tislelizumab as First-line Systemic Therapy for Patients With Advanced Hepatocellular Carcinoma"

Quick Search

Relevant Topics

Cancer Disease
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...

  Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...

Searches Linking to this Trial