ICIs and Anti-VEGF Antibody/TKIs With or Without Interventional Therapy for Advanced HCC

Official title

Immune Checkpoint Inhibitors and Anti-Vascular Endothelial Growth Factor Antibody/Tyrosine Kinase Inhibitors With or Without Interventional Therapy for Advanced HCC

Overview

This trial is designed to explore the efficacy and safety of interventional therapy combined with immune checkpoint inhibitors(ICIs) and anti-vascular endothelial growth factor(VEGF) antibody/tyrosine kinase inhibitors in the treatment of advanced hepatocellular carcinoma. Eligible participants will be divided into two groups based on their treatment plans: one receiving ICIs combined with anti-VEGF drugs, and the other receiving ICIs combined with anti-VEGF drugs alongside interventional therapy, which includes C-TACE, D-TACE, and HAIC. The specific number and interval of interventional therapy sessions will be determined according to the patient's individual condition. Researchers will closely monitor and rigorously evaluate the efficacy and safety of the treatment in participants through follow-up assessments. The primary endpoint is the objective response rate , while secondary endpoints include disease control rate, progression-free survival, overall survival, duration of response, adverse events, and serious adverse events.

Interventions

• Drug Lenvatinib
  ≥60 kg: 12 mg once daily, or \<60 kg: 8 mg once daily
• Drug Pembrolizumab
  200 mg intravenously every three weeks
• Drug Atezolizumab
  1200 mg intravenously every three weeks
• Drug Bevacizumab
  15mg/kg intravenously every three weeks
• Drug Camrelizumab
  200 mg intravenously every three weeks
• Drug Apatinib
  250mg once daily
• Procedure TACE
  The specific number and interval of interventional therapy sessions will be determined according to the patient's individual condition.
• Procedure HAIC
  The specific number and interval of interventional therapy sessions will be determined according to the patient's individual condition.
• Procedure DEB-TACE
  The specific number and interval of interventional therapy sessions will be determined according to the patient's individual condition.
• Drug Tislelizumab
  200 mg intravenously every three weeks

Primary outcome measures

• ORR, objective response rate [Time frame: 12 months after the last subject is enrolled]

Secondary outcome measures (6)

• PFS, progression free survival [Time frame: 12 months after the last subject is enrolled]
• OS, overall survival [Time frame: 12 months after the last subject is enrolled]
• DCR, disease control rate [Time frame: 12 months after the last subject is enrolled]
• DoR, duration of response [Time frame: 12 months after the last subject is enrolled]
• Adverse events (AE) [Time frame: 12 months after the last subject is enrolled]
• Serious adverse events (SAE) [Time frame: 12 months after the last subject is enrolled]

Eligibility criteria

Inclusion criteria

• Subjects voluntarily participate in the study, provide written informed consent, demonstrate good compliance, and are cooperative with follow-up.
• Age ≥18 years at the time of signing informed consent, regardless of gender.
• Diagnosis of hepatocellular carcinoma confirmed by imaging (according to AASLD criteria), histology, or cytology.
• BCLC Stage B or C.
• At least one measurable lesion per RECIST 1.1.
• ECOG score of 0-1.
• Child-Pugh liver function class A or B.
• Life expectancy ≥ 3 months.
• Adequate hematological and organ function.

Exclusion criteria

• Patients with hepatocellular carcinoma who are candidates for surgical radical cure, or have undergone radical surgery without evaluable lesions, or have a history of or are planned for liver transplantation.
• Pregnant or breastfeeding women.
• Individuals with known allergy or intolerance to recombinant humanized PD-1/PD-L1 monoclonal antibody preparations.
• Received local-regional therapy within 4 weeks before the first dose of the study drug, including but not limited to surgery, radiotherapy, hepatic artery embolism, TACE, hepatic artery infusion, radiofrequency ablation, cryoablation, or percutaneous ethanol injection.
• History of other malignant tumors within 5 years prior to screening, except for hepatocellular carcinoma.
• Presence of unhealed severe wounds, active ulcers, or untreated fractures.
• Active autoimmune disease or history of autoimmune disorders.
• Significant history of gastrointestinal diseases.
• Significant history of cardiovascular or cerebrovascular diseases.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Peking Union Medical College Hospital — Beijing

Publications

• Kudo M, Ren Z, Guo Y, Han G, Lin H, Zheng J, Ogasawara S, Kim JH, Zhao H, Li C, Madoff DC, Ghobrial RM, Kawaoka T, Gerolami R, Ikeda M, Kumada H, El-Khoueiry AB, Vogel A, Peng X, Mody K, Dutcus C, Dubrovsky L, Siegel AB, Finn RS, Llovet JM; LEAP-012 investigators. Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepato PMID 39798578

Identifiers

NCT: NCT07157969 · K7470

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗