A phase II open label, randomized clinical trial of atezolizumab with or without human recombinant IL-7 (CYT107) in advanced urothelial cancer

阿替唑单抗 医学 肿瘤科 不利影响 内科学 临床研究阶段 癌症 免疫疗法 临床试验 泌尿科 彭布罗利珠单抗
作者
Randy F. Sweis,Gurkamal Chatta,Rohit K. Jain,Helen Moon,Scott E. Delacroix,Alana Fang,Leonard D’Amico,Angela Shaulov Kask,Martin A. Cheever,Steven P. Fling,Elad Sharon,Andreanne M. Lacroix,Judith C. Kaiser,Russell K. Pachynski,Evan Y. Yu
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
标识
DOI:10.1158/1078-0432.ccr-24-1728
摘要

Abstract Purpose: Advanced urothelial cancer generally has high mortality despite modern anti-PD-1/L1 antibody-based combinations. Augmenting checkpoint inhibitor-mediated immune responses with lymphocyte growth factors may improve outcomes. We conducted a randomized phase II study (CITN-14) in 47 patients to explore whether human recombinant IL-7 (CYT107) could be safely combined with PD-L1 inhibition to enhance responses. Patients and Methods: Patients with urothelial cancer following platinum chemotherapy were randomized to atezolizumab alone or with CYT107 weekly for four doses. The primary objective was clinical efficacy by objective response rate (ORR). Secondary objectives included safety, toxicity, and other clinical outcomes. Correlative endpoints included peripheral immunophenotyping and quantification of cytokines. Results: CYT107 plus atezolizumab was well-tolerated, without dose-limiting toxicities (DLTs), and lower grade 3-4 treatment-related adverse events (TRAEs) compared to atezolizumab. The ORR was 26.3% for the combination versus 23.8% for atezolizumab alone (p = 0.428). The complete response (CR) rate was 10.5% for the combination versus 4.8% for monotherapy. Three patients on the combination had responses >21 months versus one with monotherapy. CD4+ and CD8+ T lymphocyte expansion occurred in patients with response to combination therapy, with the greatest effect in T memory stem cell (Tscm) cells. Responding patients had elevated baseline CCL4 and decreased VEGF-A and TNF. Conclusions: Combining CYT107 with atezolizumab was safe and resulted in lymphocyte expansion, a doubling of the CR rate, and durable responses exceeding 2 years, however, the ORR was similar to atezolizumab alone. Increased and sustained doses of CYT107 coupled with patient selection strategies should be further investigated.
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
猪猪hero应助sunsunsun采纳,获得10
1秒前
1秒前
2秒前
xiewen完成签到,获得积分20
4秒前
htx发布了新的文献求助30
4秒前
香蕉觅云应助羊羊羊采纳,获得10
4秒前
5秒前
8秒前
hunbaekkkkk发布了新的文献求助10
9秒前
泡泡球完成签到,获得积分10
11秒前
大模型应助dreamfly采纳,获得10
11秒前
庄冬丽发布了新的文献求助10
12秒前
12秒前
赵一丁发布了新的文献求助10
14秒前
14秒前
研友_VZG7GZ应助微微采纳,获得10
17秒前
18秒前
guoze完成签到,获得积分10
18秒前
哈尔婧发布了新的文献求助10
18秒前
猫猫头发布了新的文献求助30
20秒前
呀呀呀完成签到,获得积分10
20秒前
21秒前
魔幻擎宇发布了新的文献求助20
21秒前
MMMM完成签到,获得积分10
21秒前
量子星尘发布了新的文献求助10
22秒前
Lsc完成签到,获得积分10
24秒前
MMMM发布了新的文献求助10
25秒前
26秒前
29秒前
29秒前
30秒前
小二郎应助木水采纳,获得10
31秒前
Tingshan发布了新的文献求助10
33秒前
35秒前
Abby发布了新的文献求助10
35秒前
35秒前
Laurel完成签到,获得积分10
36秒前
自然剑发布了新的文献求助10
39秒前
CipherSage应助松鼠桂鱼采纳,获得10
39秒前
失眠的狗发布了新的文献求助10
40秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
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 3976267
求助须知:如何正确求助?哪些是违规求助? 3520472
关于积分的说明 11203425
捐赠科研通 3257089
什么是DOI,文献DOI怎么找? 1798589
邀请新用户注册赠送积分活动 877785
科研通“疑难数据库(出版商)”最低求助积分说明 806523