1015TiP - A Prospective, phase II clinical study of tislelizumab monotherapy or in combination with lenvatinib for neoadjuvant treatment of resectable hepatocellular carcinoma

Background

Surgery is the main radical treatment for hepatocellular carcinoma (HCC), but the high postoperative recurrence rate makes the survival benefit of patients limited. Some studies have shown that PD-1 antibody alone as neoadjuvant therapy induced significant tumor necrosis. In our center, Tislelizumab in combination with Lenvatinib as neoadjuvant therapy was well tolerated and significantly induced pathological and clinical response without significant surgical delay (NCT04834986). These results suggest that immunotherapy has good potential as neoadjuvant therapy in resectable liver cancer, but the characteristics of patients targeted by different regiments are not clear. This study aims to explore the factors that influence the efficacy of Tislelizumab monotherapy or in combination with Lenvatinib and accurately screen patients to further improve the safety and efficacy of neoadjuvant treatment.

Trial design

This single-center, two-arm phase II study (NCT05807776) will enroll 50 patients. The key inclusion criteria include confirmed resectable HCC, BCLC A, Child-Pugh A, ECOG PS 0-1, no prior systemic therapy. All patients will undergo pretreatment biopsy and subsequently receive 2 cycles of treatment with 200mg Tislelizumab. Tumor assessment performs in accordance with mRECIST. Patients who achieve partial response(PR) or reduced stable disease(SD) will be assigned to arm 1 and directly undergo surgical resection, start adjuvant treatment 4-8 weeks after surgery with Tislelizumab for 3-6 months. Patients who achieve progressive disease(PD) or increased SD will be assigned to arm 2, undergo second biopsy and receive Tislelizumab and Lenvatinib(8mg/kg) for 2 cycles, followed by surgical resection depends on the patient's physical condition and tumor condition, start adjuvant treatment with Tislelizumab in combination with Lenvatinib for 3-6 months. The primary endpoint is major pathologic response rate (MPR, tumor necrosis >70%), secondary endpoints are 1 and 2 years DFS rate, ORR, surgical delay rate (time from the end of last neoadjuvant treatment cycle to surgery > 28 days) and safety. Study enrollment has begun in April 2023.

Clinical trial identification

NCT05807776.

Editorial acknowledgement

Legal entity responsible for the study

Tianjin Medical University Cancer Institute and Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.