Regorafenib Combined With PD-1 Inhibitor Therapy for Second-line Treatment of Hepatocellular Carcinoma

Phase 2

Recruiting

• Conditions: Hepatocellular Carcinoma; PD-1 Inhibitor; Regorafenib
• Interventions: Drug: Regorafenib; Drug: PD-1 inhibitor

• Registration Number: NCT05048017
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

This is a single arm, nonrandomized, single center clinical study to investigate the safety and efficacy of regorafenib combined with PD-1 inhibitor therapy for second-line treatment of hepatocellular carcinoma

Detailed Description

To observe and evaluate the efficacy, safety and biomarker analysis of regorafenib combined with PD-1 inhibitor for the second-line treatment of hepatocellular carcinoma.In this study, 20 patients with hepatocellular carcinoma will be enrolled for regorafenib combined with PD-1 inhibitor therapy.In the absence of any of the following conditions, such as withdrawal of informed consent by subjects, intolerable drug side effects, or the investigator's determination that further study is not appropriate, the expected study treatment for each subject will continue until radiologically confirmed tumor progression. Efficacy indicators and safety indicators will be observed during the trial.

Study Timeline

• Study First Submitted: 2021-08-17
• Study First Submitted QC: 2021-09-15
• Study First Posted: 2021-09-17
• Study Start: 2021-10-01
• Status Verified: 2023-01
• Last Update Submitted: 2023-03-27
• Last Update Posted: 2023-03-29
• Primary Completion: 2025-11-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Regorafenib plus PD-1 inhibitor	Regorafenib	Regorafenib (BAY 73-4506, Stivarga®) is an oral diphenylurea multi-kinase inhibitor that targets angiogenic (VEGFR1-3, TIE2), stromal (PDGFR-β, FGFR), and oncogenic receptor tyrosine kinases (KIT, RET, and RAF). Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd, recently received conditional approval in China for the treatment of relapsed or refractory classical Hodgkin lymphoma. Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Shanghai Junshi Bioscience Co., Ltd in China for the treatment of various cancers. Pembrolizumab (Keytruda) the programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells.
Regorafenib plus PD-1 inhibitor	PD-1 inhibitor	Regorafenib (BAY 73-4506, Stivarga®) is an oral diphenylurea multi-kinase inhibitor that targets angiogenic (VEGFR1-3, TIE2), stromal (PDGFR-β, FGFR), and oncogenic receptor tyrosine kinases (KIT, RET, and RAF). Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd, recently received conditional approval in China for the treatment of relapsed or refractory classical Hodgkin lymphoma. Toripalimab, a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2), is being developed by Shanghai Junshi Bioscience Co., Ltd in China for the treatment of various cancers. Pembrolizumab (Keytruda) the programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	one year	A duration from the date of initial treatment to disease progression (defined by RECIST 1.1) or death of any cause

Secondary Outcome Measures

Name	Time	Method
Percentage of patients with stable disease (SD) ≥ 4 weeks	one year	It is specifically referred to the percentage of patients with identified SD that can be evaluated for efficacy.
Progression-free survival rate at 3 months	6 months	It's the percentage of patients with no disease progression or died from any cause after 3 months of treatment with combination of regorafenib and PD-1 inhibitor in the total number of patients whose efficacy can be evaluated.
Mortality at 12 months	one year and a half	It's the percentage of patients who died of any cause after 12 months treatment with combination of regorafenib and PD-1 inhibitor in total enrolled patients.
Objective Response Rate (ORR)	one year	Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients
Partial response (PR)	one year	Sum of the maximum diameters of target lesions is reduced by at least 30%, which lasts for at least 4 weeks.
Complete response (CR)	one year	Disappearance of all target lesions, no appearance of new lesions, and normalization of tumor markers last for at least 4 weeks.
Overall survival (OS)	one year	It is the time from when a subject is clearly enrolled to death from any cause.
Duration of response (DOR)	one year	It is the time from the first-time PR or CR (subject to the earlier one) objectively reported to the first-time disease progression or death.

Trial Locations

Locations (1)

Hai-Tao Zhao; 🇨🇳 Beijing, Beijing, China