Background Patients with hepatocellular carcinoma (HCC) who exceed standard Milan criteria suffered from high post-transplant recurrence rate.This study will evaluate the safety and efficacy of pembrolizumab in combination with lenvatinib as neoadjuvant therapy in participants with HCC exceeding Milan criteria before liver transplant.

Materials and Methods Participates would be randomly assigned (1:1) to experimental or Comparator/Control by computer-generated allocation based on the envelope method and the hierarchical block randomization method(hierarchy: BCLC stage and AFP level). The envelopes are sealed opaque, and sequentially numbered.Randomization is performed by the trial coordinator.The random number table and the block assignment number table will be kept confidential by the full-time secretary of this project.Center-stratified block-permuted randomization is used in this trial. Then permuted block randomization is used for each stratum with a block size of 4.

Results The initial first patient was recruited in August.2020, the primary hypothesis of this study are that neoadjuvant pembrolizumab plus lenvatinib is superior to regularly waiting in the list with respect to: 1) recurrence-free survival (RFS) as assessed by blinded independent central review (BICR); and 2) Objective Response Rate (ORR).The investigators design a clinical study to explore whether the combination above as a neoadjuvant treatment in patients with advanced HCC before liver transplant could reduce postoperative recurrence and to analyze potential immune biomarker of therapeutic response.

Conclusions The study is still ongoing and the preliminary short term outcome was positive. HCC patients who exceeded milan criteria may benefit from neoadjuvant immunotherapy combined with TKI before liver transplantation.

Disclosure Information H. Feng: None. Q. Xia: None.