Tislelizumab or Tislelizumab Combined With Lenvatinib Neo-adjuvant Treatment for Resectable RHCC

Phase 2

Recruiting

• Conditions: Recurrent Hepatocellular Carcinoma
• Interventions: Drug: Tislelizumab combined with Levatinib; Drug: Tislelizumab

• Registration Number: NCT04615143
• Lead Sponsor: Sun Yat-sen University

Brief Summary

This non-randomized phase II clinical trial aimed to explore the efficacy and safety of Tislelizumab or Tislelizumab combined with Lenvatinib as neoadjuvant treatment for resectable RHCC patients

Detailed Description

Hepatocellular carcinoma (HCC) patients have about 70% of 5-year recurrence rate after curative treatment. Only 30% of recurrent HCC (RHCC) patients are resectable when diagnosed. Neoadjuvant treatment may reduce tumor burden and recurrence rate after surgery for RHCC patients. Immune checkpoint inhibitors combined with or without antiangiogenic agents have already been reported effective in advanced HCC patients as first-line therapy, and in several early-stage solid tumors as neoadjuvant therapy. According to several preclinical results, immune infiltration and the expression of PD-1 were higher in RHCC tumors than in paired primary tumors. So, immune checkpoint inhibitors combined with or without antiangiogenic agents might have a better response in RHCC patients than primary HCC patients. Herein, we designed this phase II clinical trial to explore the efficacy and safety of Tislelizumab (PD-1 inhibitor) or Tislelizumab combined with Lenvatinib as neoadjuvant treatment for resectable RHCC patients. Enrolled resectable RHCC patients will be divided into two non-randomized seperate arms, sequentially (arm 1: neoadjuvant tislelizumab; arm 2: neoadjuvant tislelizumab and lenvatinib). Each arm was estimated to enroll 40 patients. We have already enrolled 17 patients in arm 1, and have terminated the enrollment of arm 1 due to modest treatment responses. The enrollment of arm 2 is ongoing.

Study Timeline

• Study First Submitted: 2020-10-28
• Study First Submitted QC: 2020-10-28
• Study First Posted: 2020-11-04
• Study Start: 2020-12-01
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-07
• Last Update Posted: 2025-01-09
• Primary Completion: 2026-12-01
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Diagnosed as recurrent hepatocellular carcinoma after curative treatment;
2. The criteria for resectability is met;
3. Has at least one evaluable lesion according to the RECIST 1.1 standard and has not received local treatment;
4. Eastern Cooperative Oncology Group score 0-1, Child-pugh score 5-7;
5. Agree to biopsy and blood sample collection;
6. Adequate organ and marrow function.

Exclusion Criteria

1. Previously received any transarterial chemoembolization and immune therapy and other local or systemic liver cancer treatments, except for curative ablation;
2. Extrahepatic metastasis;
3. History of gastroesophageal varices or active cardia ulcers associated with a high risk of bleeding;
4. History of autoimmune disease or need to take immunosuppressant drugs for a long time;
5. History of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
6. Abnormal organ function

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tislelizumab Combined Lenvatinib	Tislelizumab combined with Levatinib	Patients enrolled will receive Tislelizumab combined Lenvatinibas neoadjuvant treatment before surgery (Tislelizumab: 200mg q3w\*2 cycles+Lenvatinib 8/12mg qd\*4weeks) and as adjuvant treatment after surgery for 1 year
Tislelizumab	Tislelizumab	Tislelizumab is one kind of PD-1 inhibitors. Patients enrolled will receive Tislelizumab as neoadjuvant treatment before surgery (200mg q3w\*2 cycles) and as adjuvant treatment after surgery for 1 year

Primary Outcome Measures

Name	Time	Method
Disease-free survival rate	1 year	Defined as the percent of patients without recurrence, progression or death in one year after enrollment

Secondary Outcome Measures

Name	Time	Method
Objective response rate	At time of surgery	Defined as the percent of patients with a complete response (CR) or partial response (PR) documented by the Investigator per RECIST 1.1.
Incidence of severe adverse events	Three months after treatment	Defined as the percent of patients with adverse events over grade 3.
Major pathological response rate	At time of surgery	Defined as the percent of patients with less than 10% visible cancer cells out of the surface expression of the total tumor area at the time of surgery

Trial Locations

Locations (1)

The First Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China