Division of Cancer, Department of Surgery & Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, W120HS, London, UK.
Department of Translational Medicine, Università del Piemonte Orientale "A. Avogadro", Via Paolo Solaroli, 17, 28100, Novara, NO, Italy.
BMC Cancer. 2021 Mar 23;21(1):301. doi: 10.1186/s12885-021-08033-x.
After liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. There are no approved anti-cancer therapies known to affect such risk, highlighting the acute need for novel systemic therapies to control the probability of disease relapse. Immunotherapy is expanding as a novel treatment option for HCC. Emerging data from cohort 4 of the CA209-040 study, which investigated the safety and preliminary efficacy of nivolumab/ipilimumab co-administration in advanced HCC, suggest that the combination can be delivered safely with an acceptable proportion of reversible grade 3-4 toxicities (27.1%) and a low discontinuation rate (2%) in patients with HCC. Here, we describe the design and rationale of PRIME-HCC, a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab/ipilimumab combination prior to LR in early-stage HCC.
The study involves an initial safety run-in phase (Part 1) to allow for preliminary safety characterisation within the first 6 patients enrolled and a subsequent expansion (Part 2). Ipilimumab will be administered once only on Day 1. Nivolumab will be administered on Day 1 and Day 22 (± 3 days) for a total of two 21-day cycles (i.e. 6 weeks of treatment). The primary objective of the study is to determine the safety and tolerability of the nivolumab/ipilimumab combination prior to LR. The secondary objective is to preliminarily characterize the efficacy of the combination prior to LR, including objective response rate (ORR) and pathologic response rates. Additional exploratory objectives include preliminary evidence of long-term disease control and to identify predictive correlates of response to the nivolumab/ipilimumab combination in HCC.
The results of this study will help define the positioning of neoadjuvant nivolumab/ipilimumab combination in the perioperative management of HCC, with potential to improve survival outcomes in this patient population.
EudraCT Number: 2018-000987-27 Clinical trial registry & ID: ClinicalTrials.gov : NCT03682276 .
肝癌患者在接受肝切除（LR）后复发风险较高。目前尚无已知的抗癌疗法能够影响这种风险，这突显了迫切需要新的系统疗法来控制疾病复发的概率。免疫疗法作为 HCC 的一种新的治疗选择正在不断发展。来自 CA209-040 研究队列 4 的最新数据表明，纳武单抗/伊匹单抗联合治疗晚期 HCC 的安全性和初步疗效，提示该联合方案在 HCC 患者中具有良好的安全性，可接受的比例为可逆性 3-4 级毒性（27.1%）和低停药率（2%）。在这里，我们描述了 PRIME-HCC 的设计和原理，这是一项两部分、多中心、Ib 期研究，旨在评估纳武单抗/伊匹单抗联合方案在早期 HCC 患者 LR 前的安全性和生物活性。
该研究包括初始安全性探索阶段（第 1 部分），以允许在前 6 名入组患者中进行初步安全性评估，然后进行扩展（第 2 部分）。伊匹单抗将仅在第 1 天给药一次。纳武单抗将在第 1 天和第 22 天（±3 天）给药，共两个 21 天周期（即 6 周治疗）。该研究的主要目的是确定 LR 前纳武单抗/伊匹单抗联合方案的安全性和耐受性。次要目的是初步确定 LR 前联合方案的疗效，包括客观缓解率（ORR）和病理缓解率。额外的探索性目标包括初步证明长期疾病控制，并确定对 HCC 中纳武单抗/伊匹单抗联合方案反应的预测相关性。
这项研究的结果将有助于确定新辅助纳武单抗/伊匹单抗联合方案在 HCC 围手术期管理中的定位，有可能改善这一患者群体的生存结果。
EudraCT 编号：2018-000987-27 临床试验注册号：ClinicalTrials.gov：NCT03682276
