Less Frequent Intravenous Dosing of Nemvaleukin Alfa in Patients With Advanced Solid Tumors: The Phase 1/2 ARTISTRY-3 trial.

IF 4.2 2区医学 Q1 ONCOLOGY

Oncologist Pub Date : 2025-09-24 DOI:10.1093/oncolo/oyaf301

Sarina A Piha-Paul, Justin A Call, Alexander I Spira, Jorge Bartolomé, Maria de Miguel, Xiwei Chen, Sarah S Donatelli, Nehal J Lakhani

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引用次数: 0

Abstract

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 three schedules: day 1, days 1 and 8, and days 1 and 4. The primary endpoint was incidence of dose-limiting toxicities (DLTs).

Results: From April 2022 to June 2024, 52 patients received nemvaleukin. No DLTs were reported. Most nemvaleukin-related treatment-emergent 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. NK and CD8+ T-cell expansion in whole blood was observed, with minimal regulatory T-cell expansion. Nemvaleukin at 30 μg/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 and CD8+ T-cells was observed in on-treatment biopsies.

Conclusion: Less frequent IV doses of nemvaleukin demonstrated pharmacodynamic proof of mechanism and was tolerable with some disease stabilization.

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晚期实体瘤患者静脉注射Nemvaleukin - α的频率较低：1/2期ARTISTRY-3试验

背景：静脉注射（IV） nemvaleukin α (nemvaleukin, ALKS 4230)，每天1-5天，21天为周期，在重度预处理的晚期实体瘤中显示出抗肿瘤活性和可管理的安全性。我们报告了开放标签I/II期ARTISTRY-3 （NCT04592653）研究的队列2的结果，该研究评估了在晚期实体瘤中静脉给药频率较低的nevaleukin。方法：符合条件的患者以21天为周期，在第1天、第1天和第8天以及第1天和第4天接受逐步递增的静脉注射奈瓦列金剂量。主要终点是剂量限制性毒性（dlt）的发生率。结果：2022年4月至2024年6月，52例患者接受了nevaleukin治疗。未见DLTs报告。大多数与nevaleuin相关的治疗不良事件（TRAEs）为1-2级。6名患者（12%）经历了3级TRAEs，最常见的是中性粒细胞减少症。内姆瓦柳金暴露随着剂量的增加而增加。全血NK和CD8+ t细胞扩增，调节t细胞扩增最小。Nemvaleukin在第1天和第8天的剂量为30 μg/kg，是推荐的II期剂量。未观察到客观反应；16例（31%）患者病情稳定（6例(12%)≥3个月）。治疗前活检观察到肿瘤微环境中NK和CD8+ t细胞浸润增加。结论：少剂量静脉注射奈瓦柳金的药效学机制证明，可耐受，并有一定的疾病稳定。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncologist 医学-肿瘤学

CiteScore

10.40

自引率

3.40%

发文量

309

审稿时长

3-8 weeks

期刊介绍： The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.