Camrelizumab combined with Lenvatinib and RALOX-HAIC for unresectable hepatocellular carcinoma (Cal Era): a prospective, single-arm, phase II trial
Mengya Zang, Qi Li, Xiaoyun Hu, Huajin Pang, Rong Li, Wenli Li, Yongru Chen, Peilin Zhu, Kaiyan Su, Guosheng Yuan, Yuan Li, Yuanfeng Li, Jinzhang Chen
Abstract
Introduction: Combining systemic agents with hepatic arterial infusion chemotherapy (HAIC) has produced promising outcomes in advanced hepatocellular carcinoma (HCC). Raltitrexed, an antimetabolite recognized for its extended plasma half-life, enables shorter infusion schedules. This study aimed to assess the efficacy, safety, and potential predictive biomarkers of a therapeutic approach incorporating camrelizumab, lenvatinib, and a HAIC protocol using raltitrexed plus oxaliplatin (RALOX) in patients with intermediate to advanced HCC. Methods: Participants in this single-arm phase II study (NCT05003700) had Barcelona Clinic Liver Cancer (BCLC) stage B or C HCC. They received RALOX-HAIC in tandem with camrelizumab and lenvatinib for a maximum of six cycles, continuing until either disease progression or unacceptable toxicity. The primary outcome measure was the objective response rate (ORR). Results: Thirty-nine individuals underwent at least one tumor review after baseline. The confirmed ORR was 66.7% (95% CI, 49.8–80.9). The median progression-free survival was 13.8 months (95% CI, 10.5–20.5), and the median overall survival was 21.2 months (95% CI, 14.3–21.2). Grade 3-4 treatment-related adverse events occurred in 79.5% of the subjects, with the most common being decreased neutrophil count (41%), decreased platelet count (30.8%), and increased aspartate aminotransferase (23.1%). All side effects were, as anticipated, controllable, and no treatment-related deaths were reported. Serum IL2, CXCL13, and CCL19 levels significantly differed between stable disease and partial response patients (P < 0.05 and |fold change| > 1.5). Furthermore, risk stratification based on these three biomarkers revealed shorter progression-free survival and overall survival in high-risk versus low-risk subgroups (P < 0.05). These results suggested that the serum concentrations of IL-2, CXCL13, and CCL19 emerged as potential predictors of clinical benefits under this triple-combination protocol. Conclusion: The triple regimen of camrelizumab, lenvatinib, and RALOX-HAIC exhibited notable antitumor capabilities and acceptable tolerability in patients with advanced HCC. Moreover, baseline levels of IL-2, CXCL13, and CCL19 may function as predictive indicators of the response to this first-line therapeutic strategy.