Qin Albert, Ho Ming-Chih, Tsai Chan-Yen, Liu Chun-Jen, Chen Pei-Jer
Medical Research and Clinical Operations, PharmaEssentia Corporation, Taipei, Taiwan.
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
Hepatol Int. 2025 Apr 5. doi: 10.1007/s12072-025-10824-4.
BACKGROUND/PURPOSE: Post-operative recurrence is a major clinical challenge with hepatocellular carcinoma (HCC). While currently unapproved, anti-programmed cell death 1 (PD-1) and anti-vascular endothelial growth factor combination adjuvant therapy showed promise. We initiated a phase I trial using sequential treatment with ropeginterferon alfa-2b (ropeg), a novel interferon-based antiviral and antitumor agent, followed by anti-PD-1 therapeutic antibody nivolumab as an adjuvant therapy for hepatitis B virus (HBV)-related HCC.
Patients who underwent surgical resection of HBV-related HCC with curative intent received sequential therapy with six doses of ropeg every two weeks at 450 μg, followed by three doses of nivolumab escalating from 0.3 to 0.75 mg/kg every two weeks. Safety, HBV surface antigen (HBsAg) loss or decrease, anti-HBV surface (HBs) antibodies, cancer recurrence, and survival were evaluated.
Fifteen eligible patients were enrolled. Most adverse events (AEs) were mild or moderate and no severe or serious AEs were observed. Alanine transaminase flares, including one grade 3 event as dose-limiting toxicity, were noted in five cases and the final recommended dose for anti-PD1 was determined at 0.75 mg/kg. Interestingly, all five cases had HBsAg clearance or reduction. All patients in the study were alive without cancer recurrence during a median follow-up of 1024 days with six patients surviving > 4 years and three for > 5 years.
This phase I trial supports the safety and clinical efficacy of sequential treatment with ropeg and nivolumab in post-resection HBV-related HCC. This regimen holds promise for further adjuvant therapy trials in HCC, both HBV-related and other types.
背景/目的：术后复发是肝细胞癌（HCC）面临的一项重大临床挑战。虽然目前尚未获批，但抗程序性细胞死亡蛋白1（PD-1）与抗血管内皮生长因子联合辅助治疗显示出前景。我们开展了一项I期试验，采用新型基于干扰素的抗病毒和抗肿瘤药物罗哌干扰素α-2b（ropeg）序贯治疗，随后使用抗PD-1治疗性抗体纳武单抗作为乙型肝炎病毒（HBV）相关HCC的辅助治疗。
接受了具有治愈意图的HBV相关HCC手术切除的患者接受序贯治疗，每两周给予6剂450μg的ropeg，随后每两周给予3剂纳武单抗，剂量从0.3mg/kg递增至0.75mg/kg。评估安全性、HBV表面抗原（HBsAg）丢失或减少、抗HBV表面（HBs）抗体、癌症复发和生存率。
招募了15名符合条件的患者。大多数不良事件（AE）为轻度或中度，未观察到严重或重大AE。5例患者出现丙氨酸转氨酶升高，其中1例3级事件作为剂量限制性毒性，抗PD1的最终推荐剂量确定为0.75mg/kg。有趣的是，所有5例患者的HBsAg均清除或降低。研究中的所有患者在中位随访1024天期间均存活且无癌症复发，6例患者存活超过4年，3例患者存活超过5年。
这项I期试验支持ropeg和纳武单抗序贯治疗在切除术后HBV相关HCC中的安全性和临床疗效。该方案有望在HBV相关和其他类型的HCC中开展进一步的辅助治疗试验。
