The efficacy and safety of toripalimab combined with sorafenib for unresectable hepatocellular carcinoma: An open-label, prospective, single-arm phase II study.

Abstract

e16184 Background: Hepatocellular carcinoma (HCC) is often diagnosed at an advanced stage, leaving patients ineligible for surgery. Sorafenib is a first-line therapy, but disease progression still occurs in most patients within a year. Toripalimab, an immune checkpoint inhibitor has demonstrated promising efficacy and safety in various solid tumors, and its combination with Sorafenib may alter outcomes in HCC patients. This study aims to assess the safety and efficacy of Toripalimab plus Sorafenib for the treatment of advanced HCC. Methods: This is a single-arm, open-label, prospective phase II clinical trial (NCT04926532) for patients with unresectable HCC. Participants receive Toripalimab (240mg, iv, d1) and Sorafenib (400mg, bid, po, d1-21) every 3 weeks until disease progression or unacceptable toxicity occurs. The primary endpoints are objective response rate (ORR) evaluated with RECIST v1.1 and safety. Secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response (DOR). Exploratory endpoints comprise monitoring indicators for the efficacy and sensitivity of immunotherapy drugs. Results: As of January 17, 2023, 28 patients were enrolled, with a median age of 59.8 years and 85.7% were male. All patients had Child-Pugh A classification. The median follow-up time was 14.7 months (2.3-31.3). The distribution of patients by CNLC stage was as follows: Ib/IIa/IIb/IIIa/IIIb stage were 25.0%, 17.9%, 25.0%, and 32.1%, respectively. Among all patients, 6 (21.4%) had distant metastasis, 7 (25.0%) had portal vein tumor thrombus (PVTT), and 3 (10.7%) had hepatic vein invasion. The ORR was 35.7% and DCR was 71.4%. Of the 28 patients, 3 (10.7%) achieved complete response (CR), and 7 (25.0%) achieved partial response (PR). The median DOR was 2.7 months (95% CI: 0.9-16.9). The median PFS was 4.8 months (95% CI: 3.1-18.9), and the median OS was not reached (95% CI: NA-NA). 6 patients (21.4%) underwent surgical resection, and 3 of them (50.0%) experienced postoperative recurrence. The median PFS of patients who underwent surgery was 20.4 months (95% CI: 12.6-NA). 6 patients (21.4%) withdrew due to adverse events (AEs). Treatment-related adverse events (TRAEs) occurred in 26/28 patients (92.9%). Grade 1-2 TRAEs occurred in 10/28 patients (35.7%), Grade 3 TRAEs occurred in 11/28 patients (39.3%), and no grade 4-5 TRAEs were observed. This study is currently ongoing. Conclusions: Toripalimab combined with Sorafenib demonstrated encouraging efficacy and tolerable toxicity as a first-line option for patients with unresectable HCC, with some patients achieving tumor downstaging and surgical resection. This combination could be considered an optional regimen for the first-line treatment of unresectable HCC. Clinical trial information: NCT04926532 .