Camrelizumab combined with Lenvatinib and RALOX-HAIC for unresectable hepatocellular carcinoma (Cal Era): a prospective, single-arm, phase II trial

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.