Abstract：
NKTR-255 is an investigational polyethylene glycol-modified recombinant human IL-15 (rhIL-15) receptor agonist, designed to improve the immunotherapeutic and anti-cancer benefit observed with rhIL-15 while circumventing the toxicities associated with this therapy. In preclinical studies, NKTR-255 has demonstrated enhanced proliferation and function of CD8+ T cells and natural killer cells, as well as enhanced anti-tumor activity and survival both as monotherapy and in combination with monoclonal antibodies in multiple cancer models. Here, we describe the rationale and design of the first-in-human Phase I, dose-escalation and dose-expansion study of NKTR-255 alone and in combination with daratumumab or rituximab in adults with relapsed/refractory multiple myeloma or non-Hodgkin\'s lymphoma that will determine the maximum tolerated dose and recommended Phase II dose for NKTR-255.
Lay abstract Interleukin-15 (IL-15) is a protein that helps the body\'s natural immune system to defend itself against infections and diseases like cancer. This article discusses a clinical trial in patients with multiple myeloma or non-Hodgkin\'s lymphoma that evaluates a new investigational medicine, NKTR-255, a polymer-modified form of IL-15 that has been engineered to improve its ability to provide a sustained anti-tumor immune response. The trial will explore different doses of NKTR-255 to determine patient side effects and to find the highest acceptable dose that patients can tolerate. Based on this, a dose will be chosen that offers an optimal balance between having a positive anti-cancer effect and minimizing side effects. This dose will be tested further in patients who have had different treatments in the past. If the side effects are acceptable, this dose will be tested in a new trial in a large number of patients. Clinical Trial Registration: NCT04136756 (ClinicalTrials.gov).
Lay abstract Interleukin-15 (IL-15) is a protein that helps the body\'s natural immune system to defend itself against infections and diseases like cancer. This article discusses a clinical trial in patients with multiple myeloma or non-Hodgkin\'s lymphoma that evaluates a new investigational medicine, NKTR-255, a polymer-modified form of IL-15 that has been engineered to improve its ability to provide a sustained anti-tumor immune response. The trial will explore different doses of NKTR-255 to determine patient side effects and to find the highest acceptable dose that patients can tolerate. Based on this, a dose will be chosen that offers an optimal balance between having a positive anti-cancer effect and minimizing side effects. This dose will be tested further in patients who have had different treatments in the past. If the side effects are acceptable, this dose will be tested in a new trial in a large number of patients. Clinical Trial Registration: NCT04136756 (ClinicalTrials.gov).
摘要：
NKTR-255是一种研究性聚乙二醇修饰的重组人IL-15（rhIL-15）受体激动剂，旨在改善rhIL-15观察到的免疫治疗和抗癌益处，同时规避与该疗法相关的毒性。在临床前研究中,NKTR-255已证明CD8+T细胞和自然杀伤细胞的增殖和功能增强，以及在多种癌症模型中作为单一疗法和与单克隆抗体联合使用增强的抗肿瘤活性和生存率。这里,我们描述了人类第一阶段的基本原理和设计，在复发性/难治性多发性骨髓瘤或非霍奇金淋巴瘤成人患者中,NKTR-255单独及联合达雷妥单抗或利妥昔单抗的剂量递增和剂量扩大研究将确定NKTR-255的最大耐受剂量和推荐II期剂量.白细胞介素-15（IL-15）是一种蛋白质，可以帮助人体的自然免疫系统抵御感染和癌症等疾病。本文讨论了一项针对多发性骨髓瘤或非霍奇金淋巴瘤患者的临床试验，该临床试验评估了一种新的研究药物，NKTR-255，一种聚合物修饰形式的IL-15，已被设计为改善其提供持续抗肿瘤免疫应答的能力。该试验将探索不同剂量的NKTR-255，以确定患者的副作用，并找到患者可以耐受的最高可接受剂量。基于此,将选择在具有积极抗癌效果和最小化副作用之间提供最佳平衡的剂量。该剂量将在过去接受过不同治疗的患者中进一步测试。如果副作用可以接受，该剂量将在大量患者的新试验中进行测试。临床试验注册：NCT04136756（ClinicalTrials.gov）。
