Abstract 486: A phase Ib/II, open-label study evaluating the efficacy and safety of Toripalimab injection (JS001) or combination with Lenvatinib as a neoadjuvant therapy for patients with resectable hepatocellular carcinoma (HCC)
Authors: Shi Ying-Hong , Ji Yuan , Liu Wei-Ren , Pang Yan-Rui , Ding Zhen-Bin , Fu Xiu-Tao , Zhang Xin , Huang Cheng , Sun Yun-Fan , Zhu Xiao-Dong , Sun Hui-Chuan , Zhou Jian , Fan Jia 
Published: July 2021

Background: There is no standard of care for neoadjuvant or adjuvant therapy for resectable hepatocellular carcinoma (HCC) yet. This trial is designed to explore the safety and efficacy of toripalimab or toripalimab in combination of lenvatinib as peri-operative treatment in HCC. (NCT03867370)

Methods: In this ongoing phase Ib/II trial, patients (pts) with HCC who are eligible for surgical resection are enrolled. In neoadjuvant part of study, pts in Arm A are given toripalimab 480 mg iv single dose and pts in Arm B are treated with toripalimab 480mg iv plus concurrent lenvatinib 12 or 8 mg daily orally (based on body weight). All pts receive scheduled surgery on day 21-28. Lenvatinib is given until at least 7 days before surgery. Pts with R0 section confirmed by pathological analysis and MRI 4 weeks after surgery can take part in the adjuvant part of study. Toripalimab at 240 mg iv is given every 3 weeks for 48 weeks in Arm A. Pts in Arm B 1:1 randomized to receive toripalimab per same schedule as Arm A or toripalimab plus concurrent lenvatinib for 48 weeks. The primary objective is the pathological response. Secondary objectives include safety/tolerability, ORR, DCR, time to operation and PFS.

Results: From 1 June 2019 to 7 Sep 2020, 18 pts were enrolled (10 in Arm A and 8 in Arm B) and 16 pts were evaluable. Two pts withdrew consent, one was due to the Covid-19 pandemic, and another received liver transplantation subsequently. The HCC in 11 pts were BCLC A stage, 4 pts were BCLC 0 and 1 pt BCLC B. 14 patients were in Chinese HCC staging CNLC Ia, 2 pts were in CNLC Ib. 81.3% patients were recurrent HCC. 16.7% (3/18) of patients experienced Grade 3+ AEs, 1 patient in Arm B experienced

treatment-related SAE (hyperglycemia, well controlled). 16 pts (8 in Arm A and 8 in Arm B) proceeded with resection as planned. There were no delays or cancellations in surgery related to immunotherapy or target treatment. No visible tumor was observed in resected specimen in one patient. No pathological complete response (pCR) was observed in other 15 pts. 3 pts (20%) achieved major pathologic response (MPR, residual tumor in &lt;50% tumor bed) and 2 in Arm A and 1 in Arm B. Multiple immunohistochemistry analysis of the immune infiltrates in the tumor microenvironment showed an increase in T-cell infiltration in MPR tumor tissue compared with non-response tumor tissue.

Conclusion: PD-1 inhibition with toripalimab or toripalimab plus multikinase inhibition with lenvatinib result in promising antitumor activity as preoperative therapy in resectable HCC. There were no new or unexpected toxicities resulting from combination.

Citation Format: Ying-Hong Shi, Yuan Ji, Wei-Ren Liu, Yan-Rui Pang, Zhen-Bin Ding, Xiu-Tao Fu, Xin Zhang, Cheng Huang, Yun-Fan Sun, Xiao-Dong Zhu, Hui-Chuan Sun, Jian Zhou, Jia Fan. A phase Ib/II, open-label study evaluating the efficacy and safety of Toripalimab injection (JS001) or combination with Lenvatinib as a neoadjuvant therapy for patients with resectable hepatocellular carcinoma (HCC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 486.