A phase 1 dose‐escalation study of LY3295668 erbumine as monotherapy and in combination with topotecan and cyclophosphamide in children with relapsed/refractory neuroblastoma

拓扑替康 医学 神经母细胞瘤 联合疗法 耐火材料(行星科学) 中性粒细胞减少症 环磷酰胺 粘膜炎 队列 不利影响 肿瘤科 胃肠病学 毒性 内科学 外科 化疗 细胞培养 遗传学 天体生物学 生物 物理
作者
Steven G. DuBois,Chitose Ogawa,Lucas Moreno,Yaël P. Mossé,Matthias Fischer,Anne L. Ryan,Kieuhoa T. Vo,Bram De Wilde,Alba Rubio‐San‐Simón,Margaret E. Macy,Lisa Howell,Suzanne Shusterman,Nadège Corradini,Roberto Luksch,Isabelle Aerts,Jennifer H. Foster,Brian Weiss,C Karthik,Eunice Yuen,Emin Avşar
出处
期刊:Cancer [Wiley]
卷期号:131 (4)
标识
DOI:10.1002/cncr.35751
摘要

Abstract Background This study evaluated the safety, pharmacokinetics, and antitumor activity of LY3295668 erbumine as monotherapy and combination therapy in children with relapsed/refractory neuroblastoma. Methods Patients aged 2–21 years who had relapsed/refractory neuroblastoma were enrolled. LY3295668 erbumine was evaluated at two dose levels (12 and 15 mg/m 2 ) and administered orally twice daily continuously as monotherapy and in combination with intravenous topotecan and cyclophosphamide in 28‐day cycles. Results Twenty‐five patients were treated. No dose‐limiting toxicity occurred in monotherapy; one patient had dose‐limiting toxicities in the combination therapy cohort (grade 3 mucositis and grade 4 neutropenia). The recommended phase 2 dose for both monotherapy and combination therapy was 15 mg/m 2 . Twenty‐two patients (88%) had one or more treatment‐related adverse event(s) (TRAEs), and 18 (72%) experienced grade ≥3 TRAEs. Myelosuppression was the most common high‐grade TRAE observed in the combination therapy cohort. At both dose levels, steady‐state plasma concentrations exceeded xenograft 90% inhibitory concentration levels. In the monotherapy cohort, one patient had a minor response, and one patient had stable disease, both continuing for >12 months. In the combination therapy cohort, two patients had a partial response, two had a minor response, and six had stable disease. Overall, the response rate, according to New Approaches to Neuroblastoma Therapy version 2.0 criteria, was 8%, and the disease control rate was 52%. Conclusions LY3295668 erbumine had a manageable safety profile as monotherapy and in combination therapy. Although proof‐of‐concept clinical responses were observed, future studies with biomarker‐selected populations and/or novel combinations may yield higher response rates with Aurora kinase A inhibition.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
RNNNLL完成签到,获得积分10
刚刚
搜集达人应助大力的诗蕾采纳,获得10
2秒前
4秒前
lanyun00123关注了科研通微信公众号
6秒前
秋不落棠发布了新的文献求助10
7秒前
7秒前
8秒前
自然友菱完成签到,获得积分10
9秒前
领导范儿应助xkyasc采纳,获得10
10秒前
在水一方应助luo采纳,获得10
10秒前
11秒前
20011013完成签到 ,获得积分10
11秒前
iNk应助微微采纳,获得10
11秒前
12秒前
12秒前
飞乐扣完成签到 ,获得积分10
13秒前
粗暴的君浩完成签到,获得积分10
13秒前
在水一方应助emm采纳,获得10
14秒前
17秒前
高文琴完成签到,获得积分10
17秒前
量子星尘发布了新的文献求助10
17秒前
monoklatt发布了新的文献求助10
18秒前
查查完成签到,获得积分10
18秒前
19秒前
必中发布了新的文献求助10
19秒前
所所应助jiang采纳,获得10
20秒前
李健应助HelloKun采纳,获得10
21秒前
晚风完成签到,获得积分10
21秒前
21秒前
默默雅阳发布了新的文献求助10
22秒前
勤恳的不二完成签到,获得积分10
22秒前
FashionBoy应助狂野忆文采纳,获得10
23秒前
hx完成签到,获得积分10
23秒前
SciGPT应助狂野忆文采纳,获得10
23秒前
小马甲应助狂野忆文采纳,获得10
23秒前
单薄的夜南应助狂野忆文采纳,获得10
23秒前
water应助狂野忆文采纳,获得10
23秒前
water应助狂野忆文采纳,获得10
23秒前
water应助狂野忆文采纳,获得10
23秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Toward a Combinatorial Approach for the Prediction of IgG Half-Life and Clearance 500
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3969940
求助须知:如何正确求助?哪些是违规求助? 3514642
关于积分的说明 11175298
捐赠科研通 3249947
什么是DOI,文献DOI怎么找? 1795178
邀请新用户注册赠送积分活动 875617
科研通“疑难数据库(出版商)”最低求助积分说明 804891