Toripalimab plus hepatic artery infusion chemotherapy in hepatocellular carcinoma patients of Barcelona Clinic Liver Cancer stage C: A biomolecular exploratory, phase II trial.

536 Background: Hepatic arterial infusion chemotherapy (HAIC), and immune checkpoint inhibitors showed promising results for advanced hepatocellular carcinoma. Considering different anti-malignancy mechanisms, combining these two treatments may improve outcomes. This study aimed to evaluate the efficacy and safety of toripalimab (a PD-1 inhibitor) in combination with HAIC for advanced hepatocellular carcinoma (HCC). Methods: In this single-center, single-arm, biomolecular exploratory, prospective phase II trial, HCC patients of BCLC stage C underwent the treatment of toripalimab in combination of FOLFOX-HAIC. The primary endpoint was progression-free survival (PFS) per RECIST v1.1. It has been more than 48 months since the last patient was enrolled, with long-term follow-up to fully assess the benefit of this combination treatment. Luminex cytokine microarray examined 48 most common human cytokines in pre-treatment plasma specimens from enrolled patients to explore molecular markers for predicting efficacy. Results: Between May 20, 2019 and April 26, 2021, twenty-one patients were enrolled. The primary endpoint was a median PFS of 11.93 months [95% confidence interval (CI), 4.57–37.57], and the median overall survival (OS) was 27.57 months (95% CI, 15.63–NA). The objective response rate was 61.90% per RECIST v1.1 and 66.67% per mRECIST, respectively. The most common adverse events were neutropenia and increased alanine aminotransferase level. Exploratory analyses of luminex cytokine microarray suggested that patients with low level of leukemia inhibit factor (LIF) were more likely to be benefit from this combination therapy. Conclusions: Toripalimab in combination with FOLFOX-HAIC demonstrated promising antitumor activity with favorable tolerability as first-line therapy in HCC of BCLC stage C. LIF expression level may be a promising molecular marker for predicting the efficacy of this combination therapy. Clinical trial information: NCT03851939 . Best observed treatment response. All patients (n=21) RECISTv1.1 (n=21) mRECIST (n=21) CR 0 4 (19.05%) PR 13 (61.90%) 10 (47.62%) SD 4 (19.05%) 3 (14.29%) PD 4 (19.05%) 4 (19.05%) ORR, n (%) 13 (61.90%) 14 (66.67%)