Camrelizumab combined with lenvatinib and RALOX-HAIC for hepatocellular carcinoma (HCC) in BCLC stage B and C: A prospective, single-arm, phase II trial (Cal Era study).

Abstract

e16128 Background: The combination of systemic therapies and hepatic arterial infusion chemotherapy (HAIC) showed promising outcomes for advanced hepatocellular carcinoma (HCC). Raltitrexed, an antimetabolic drug with long plasma concentrations half-life, could be used in short infusions. HAIC with raltitrexed plus oxaliplatin (RALOX) was reported to be effective and safe in HCC. This study aimed to investigate the efficacy and safety of combined camrelizumab and lenvatinib plus RALOX-HAIC as a first-line treatment in advanced HCC patients. Methods: This single-arm, phase II study included treatment-naive adult (≥18 years) patients with HCC in BCLC stage B and C and Child-Pugh score small or equal to 7 points (NCT05003700). Patients were administrated with RALOX-HAIC (oxaliplatin 100mg/m2, raltitrexed 3 mg/m2, every 3 weeks), combined with camrelizumab (200mg by IV infusion, every 3 weeks) and lenvatinib (8mg orally once daily) for 6 cycles, followed by maintenance therapy with camrelizumab and lenvatinib until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Results: Between March 2021 and October 2022, 36 patients (33 men and 3 women; median age, 54.5 years) were enrolled. The median tumor size was 11.4 cm, 86.1% of patients had portal vein invasion, and 38.9% had extrahepatic metastasis. As of February 1, 2023, the median follow-up was 14.2 months, and all patients had at least one post-baseline tumor assessment. The confirmed ORR per RECIST v1.1 and per mRECIST was respectively 61.1% (95% CI, 44.4−77.8), and 83.3% (95% CI, 70.5−96.1) including 4(11.1%) patients who achieved a complete radiological response. The median progression-free survival (PFS) time was 13.8 months (95%CI, 8.8-20.5) per RECIST v1.1. The 6-month and 12-month overall survival rate were 94.3% and 64.9%, respectively. Grade 3-4 treatment-related adverse events (AEs) occurred in 75% of patients, and the most common were neutropenia (44.4%) thrombocytopenia (36.1%), elevated aspartate aminotransferase (25.0%), and leucopenia (19.4%). All AEs were expected and manageable, and no treatment-related deaths were reported. Conclusions: Combination treatment with camrelizumab and lenvatinib plus RALOX-HAIC showed promising antitumor activity and acceptable toxicity in patients with advanced HCC. Clinical trial information: NCT05003700 .