一项 Ib 期随机多中心试验，分离肝灌注联合伊匹单抗和纳武单抗治疗葡萄膜黑色素瘤转移（SCANDIUM II 试验）。
A phase Ib randomized multicenter trial of isolated hepatic perfusion in combination with ipilimumab and nivolumab for uveal melanoma metastases (SCANDIUM II trial).
发表日期：2024 Jul 02
作者：
R Olofsson Bagge, A Nelson, A Shafazand, C Cahlin, A Carneiro, H Helgadottir, M Levin, M Rizell, G Ullenhag, S Wirén, P Lindnér, J A Nilsson, L Ny
来源：
ESMO Open
摘要：
葡萄膜黑色素瘤 (UM) 是一种罕见的恶性肿瘤，50% 的患者会出现主要影响肝脏的转移性疾病。约 40% 的转移性 UM 患者对大剂量美法仑一次性隔离肝灌注 (IHP) 有反应。该 IHP 试验研究 IHP 联合易普利姆玛 (IPI) 和纳武单抗 (NIVO) 的安全性和临床疗效。在该 IHP 试验中，未接受过免疫治疗的患者被随机分配接受 IHP 治疗，随后接受 IPI 3 mg/kg 和 NIVO 1 mg /kg (IPI3/NIVO1) 四个周期（术后组），或术前 IPI3/NIVO1、IHP 一个周期，然后 IPI3/NIVO1 三个周期（术后组），然后进行 NIVO 维持治疗480 mg，持续 1 年。18 名患者被纳入并随机分组。三名患者没有按计划接受 IHP。总共有 11/18 名患者（术后组 6 名，术前组 5 名）未完成计划的四个 IPI3/NIVO1 周期。两组的 IHP 毒性相似，但术前组的免疫相关不良事件 (AE) 数量较高。在可评估的患者中，术后组的总体缓解率为 57% (4/7)，术前组的总体缓解率为 22% (2/9)。IHP 和 IPI3/NIVO1 的联合治疗与严重的不良事件。这种组合的疗效令人鼓舞，反应率很高。在 IHP 之前进行一个周期的术前 IPI/NIVO 并未显示出安全性或有效性方面的潜在益处。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。
Uveal melanoma (UM) is a rare malignancy where 50% of patients develop metastatic disease primarily affecting the liver. Approximately 40% of patients with metastatic UM respond to one-time isolated hepatic perfusion (IHP) with high-dose melphalan. This phase I trial investigates the safety and clinical efficacy of IHP combined with ipilimumab (IPI) and nivolumab (NIVO).Immunotherapy-naïve patients were randomized in this phase I trial to receive either IHP followed by IPI 3 mg/kg and NIVO 1 mg/kg (IPI3/NIVO1) for four cycles (post-operative arm), or one cycle of preoperative IPI3/NIVO1, IHP and then three cycles of IPI3/NIVO1 (pre-post-operative arm), followed by maintenance therapy with NIVO 480 mg for 1 year.Eighteen patients were enrolled and randomized. Three patients did not undergo IHP as planned. In total, 11/18 patients (6 in the post-operative arm and 5 in the pre-post-operative arm) did not complete the planned four cycles of IPI3/NIVO1. Toxicity to IHP was similar in both groups, but the number of immune-related adverse events (AEs) was higher in the pre-post-operative arm. Among assessable patients, overall response rate was 57% in the post-operative arm (4/7) and 22% in the pre-post-operative arm (2/9).Combination therapy with IHP and IPI3/NIVO1 was associated with severe AEs. The efficacy of this combination is encouraging with high response rates. One cycle of preoperative IPI/NIVO before IHP did not show potential benefits in terms of safety or efficacy.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.