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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
晚期实体瘤患者中 nemvaleukin alfa 的低频静脉给药：1/2 期 ARTISTRY-3 试验
英文原题：Less frequent intravenous dosing of nemvaleukin alfa in patients with advanced solid tumors: the phase 1/2 ARTISTRY-3 trial.
查看英文原题
Less frequent intravenous dosing of nemvaleukin alfa in patients with advanced solid tumors: the phase 1/2 ARTISTRY-3 trial.
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研究概要
更低频次的静脉注射 nemvaleukin 显示出药效学机制验证，且可耐受，并伴有一定程度的疾病稳定。
中文摘要
背景
既往研究显示，在21天周期的第1–5天每日静脉给予nemvaleukin alfa（nemvaleukin，ALKS 4230），对经多线治疗的晚期实体瘤具有抗肿瘤活性，且安全性可管理。本研究报告开放标签I/II期ARTISTRY-3研究（NCT04592653）队列2结果，该队列评估了nemvaleukin较低频次静脉给药治疗晚期实体瘤的效果。
方法
符合条件的患者在21天周期内接受递增剂量静脉nemvaleukin，给药方案为第1天、第1和8天，或第1和4天。主要终点为剂量限制性毒性（DLT）的发生率。
结果
2022年4月至2024年6月，共52例患者接受nemvaleukin治疗，未报告DLT。大多数治疗相关不良事件（TRAE）为1–2级；6例患者（12%）发生3级TRAE，最常见为中性粒细胞减少。nemvaleukin暴露量随剂量递增而增加。观察到全血中NK细胞和CD8+ T细胞扩增，而调节性T细胞扩增很少。推荐的II期剂量为30 μg/kg，于第1和8天给药。未观察到客观缓解；16例（31%）患者疾病稳定，其中6例（12%）稳定持续3个月。治疗期间活检显示肿瘤微环境中NK细胞和CD8+ T细胞浸润增加。
结论
较低频次静脉给予nemvaleukin可显示药效学机制证据，且具有良好耐受性，并使部分患者疾病稳定。
展开英文摘要原文
BACKGROUND
Intravenous (IV) nemvaleukin alfa (nemvaleukin, ALKS 4230) administered daily on days 1-5 in 21 day cycles demonstrated antitumor activity and manageable safety in heavily pretreated advanced solid tumors. We present results from cohort 2 of the open-label phase I/II ARTISTRY-3 (NCT04592653) study, which evaluated less frequent IV dosing of nemvaleukin in advanced solid tumors.
METHODS
Eligible patients received escalating IV nemvaleukin doses in 21-day cycles on 3 schedules: day 1, days 1 and 8, and days 1 and 4. The primary endpoint was the incidence of dose-limiting toxicities (DLTs).
RESULTS
From April 2022 to June 2024, 52 patients received nemvaleukin. No DLTs were reported. Most treatment-related adverse events (TRAEs) were grade 1-2. Six patients (12%) experienced grade 3 TRAEs, the most common being neutropenia. Nemvaleukin exposure increased with escalating doses. Natural killer (NK) cell and CD8+ T-cell expansion in whole blood was observed, with minimal regulatory T-cell expansion. Nemvaleukin at 30 g/kg on days 1 and 8 was the recommended phase II dose. No objective responses were observed; 16 (31%) patients had stable disease (6 [12%] for 3 months). Increased tumor microenvironment infiltration of NK cells and CD8+ T-cells was observed in on-treatment biopsies.
CONCLUSIONS
Less frequent IV doses of nemvaleukin demonstrated pharmacodynamic proof of mechanism and were tolerable with some disease stabilization.
论文信息
- 作者
- Piha-Paul SA、Call JA、Spira AI、Bartolomé J、de Miguel M、Chen X、Donatelli SS、Lakhani NJ
- 第一作者单位
- Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States.United States
- 通讯作者单位
- START Midwest, Grand Rapids, MI 49546, United States.United States
- 文献类型
- I 期临床试验 · II 期临床试验 · 多中心研究
- 期刊
- The oncologist2025 Oct 1
- 原文标识
- PubMed 40990800 · DOI 10.1093/oncolo/oyaf301
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