Comparing the Combination of Trastuzumab and Regorafenib With Regorafenib Monotherapy for Advanced Hepatocellular Carcinoma After First-line Treatment

NCT07078305 | Not Yet Recruiting Phase 2

• 1 other identifier: E20250415
• Study Type: interventional
• Target: 134
• Locations: 0 countries
• Sites: N/A

Brief Summary

At present, there is no standard treatment plan for hepatocellular carcinoma after the progress of first-line target immunotherapy. Based on the above research background, we believe that the combination of PD-1 inhibitors and multi-target inhibitors is a promising treatment option for second-line liver cancer. Our study aims to explore the efficacy and safety of trastuzumab monoclonal antibody combined with regorafenib compared to regorafenib monotherapy for second-line treatment of advanced hepatocellular carcinoma after previous target immunotherapy progression.

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; Regorafenib; Tislelizumab

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression free survival

  1 year

Secondary Outcomes (4)

• ORR

  6 months

• DCR

  6 months

• OS

  1 year

• AE

  6 months

Study Arms (2)

Experimental group

EXPERIMENTAL

Drug: Regorafenib and tislelizumab

Control group

ACTIVE COMPARATOR

Drug: Regorafenib

Interventions

Regorafenib and tislelizumab DRUG

Tislelizumab: 200mg, iv, d1, Q3W; Regorafenib: 40-120mg, po, qd, d1-21, d22-d28 discontinuation Q4W

Experimental group

Regorafenib DRUG

Regorafenib: 40-120mg, po, qd, d1-21, d22-d28 discontinuation Q4W

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign a written informed consent form;
• Age ≥ 18 years old, both male and female are eligible;
• Hepatocellular carcinoma (HCC) diagnosed by organization/pathology or imaging that meets the AASLD diagnostic criteria;
• HCC that has received targeted immunotherapy in the past (regardless of whether local treatment is received or not, excluding neoadjuvant therapy), including atezolizumab+bevacizumab, sintilizumab+bevacizumab analogs, carizolizumab+apatinib, and other PD-1/L1 drugs+TKI, and whose disease progression has been confirmed by imaging;
• Child Pugh score ≤ 7;
• According to RECIST 1.1 criteria, there must be at least one measurable lesion;
• ECOG PS score 0-1;
• Expected survival period greater than 12 weeks;
• The function of important organs meets the following requirements (excluding the use of any blood components and cell growth factors within 14 days):
• Blood routine:
• Neutrophils ≥ 1.5 × 109/L Platelet count ≥ 80 × 109/L Hemoglobin ≥ 90g/L;
• Liver and kidney function:
• Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance rate ≥ 50 ml/min (Cockcroft Gault formula); Total bilirubin (TBIL) ≤ 3 times the upper limit of normal (ULN); AST or ALT levels ≤ 5 times the upper limit of normal (ULN); Urinary protein\<2+; If urine protein is ≥ 2+, the 24-hour urine protein quantification must show protein ≤ 1g;
• Normal coagulation function, no active bleeding or thrombotic diseases
• International Standardization Ratio INR ≤ 1.5 × ULN;

You may not qualify if:

• The subject has previous or concurrent malignant tumors (excluding cured skin basal cell carcinoma and cervical carcinoma in situ);
• It is known that the subject has a history of allergies to large molecule protein preparations, or is known to be allergic to the investigational drug or drug components;
• Within the past 6 months, there have been incidents of esophageal or gastric variceal bleeding caused by portal hypertension; Within 3 months prior to the first administration, severe (G3) varicose veins were identified through endoscopic examination; Evidence of portal hypertension (including imaging findings of splenomegaly), assessed by researchers as high-risk for bleeding
• Any life-threatening bleeding events that have occurred within the past 3 months, including the need for blood transfusion therapy, surgery or local treatment, and continuous medication therapy
• Subjects with any active autoimmune disease or history of autoimmune disease (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, those who have undergone thyroid surgery in the past cannot be included; subjects with vitiligo or complete remission of childhood asthma without any intervention in adulthood can be included; subjects with asthma requiring bronchodilators for medical intervention cannot be included);
• The subject is currently using immunosuppressants, systemic, or absorbable local hormone therapy to achieve immunosuppression (dose\>10mg/day prednisone or other therapeutic hormones), and has continued to use it within 2 weeks before enrollment;
• Ascites or pleural effusion with clinical symptoms that require therapeutic puncture or regular drainage (≥ 1 time/month);
• Patients with uncontrolled clinical symptoms or diseases of the heart, such as: (1) NYHA grade 2 or above heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, and (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
• The subject has an active infection or an unexplained fever greater than 38.5 degrees Celsius during the screening period or before the first administration (according to the researcher's judgment, the subject can be included if the fever is caused by the tumor);
• Patients with objective evidence of past and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe impairment of lung function, etc;
• Subjects with congenital or acquired immune dysfunction, such as HIV infected individuals;
• Within less than 4 weeks before the study medication, or possibly during the study period, receiving a live vaccine;
• The subject is known to have a history of substance abuse, alcoholism, or drug use;
• Have received Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications within 2 weeks before the first administration.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

regorafenib; tislelizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2025
• First Posted: July 22, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: July 22, 2025

Record last verified: 2025-07