亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials

医学 吉西他滨 鼻咽癌 内科学 顺铂 肿瘤科 临床研究阶段 化疗 放射治疗
作者
Wenfeng Fang,Yunpeng Yang,Yuxiang Ma,Shaodong Hong,Lizhu Lin,Xiaohui He,Jianping Xiong,Ping Li,Hongyun Zhao,Yan Huang,Yang Zhang,Likun Chen,Ningning Zhou,Yuanyuan Zhao,Xue Hou,Qing Yang,Li Zhang
出处
期刊:Lancet Oncology [Elsevier BV]
卷期号:19 (10): 1338-1350 被引量:416
标识
DOI:10.1016/s1470-2045(18)30495-9
摘要

Summary

Background

Platinum-based doublet chemotherapy regimens, preferentially gemcitabine plus cisplatin, are generally considered the first-line standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma. However, no consensus has been reached regarding treatment following progression after first-line therapy. Camrelizumab (SHR-1210) is a humanised anti-programmed death-1 (anti PD-1) antibody. We present safety and preliminary antitumour activity of camrelizumab alone as second-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma and combined with gemcitabine and cisplatin as first-line therapy in this patient population.

Methods

We report the results from two single-arm, phase 1 trials. Both trials included patients aged 18–70 years with histologically or cytologically confirmed nasopharyngeal carcinoma and confirmed metastatic disease or locoreginal recurrence, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients who received at least one previous line of treatment were enrolled at five academic hospitals in China into the dose-escalation and expansion trial to receive camrelizumab monotherapy intravenously at escalating doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg, and a bridging dose of 200 mg per dose once every 2 weeks (monotherapy trial). Treatment-naive patients were enrolled from a single centre in China to receive six cycles of camrelizumab 200 mg (day 1), gemcitabine 1 g/m2 (days 1 and 8), and cisplatin 80 mg/m2 (day 1) every 3 weeks followed by camrelizumab 200 mg maintenance once every 3 weeks (combination trial). The primary endpoint of both trials was the safety and tolerability of the study treatment. Analyses were done per protocol. Both trials are registered with ClinicalTrials.gov, number NCT02721589 (camrelizumab monotherapy trial) and NCT03121716 (camrelizumab combination trial). Both trials are ongoing, but are no longer enrolling patients.

Findings

In the camrelizumab monotherapy trial, between March 31, 2016, and Sept 20, 2017, 121 patients were assessed for eligibility, of whom 93 patients were enrolled across the dose-escalation and expansion cohorts and received at least one dose of camrelizumab (safety population). 15 (16%) of 93 patients had treatment-related adverse events of grade 3 or 4, the most common of which were elevated conjugated bilirubin concentration (three [3%] of 93 patients), stomatitis, anaemia, and increased concentrations of aspartate aminotransferase, alanine aminotransferase, and total bilirubin, each of which occurred in two (2%) patients. Eight (9%) patients had a treatment-related serious adverse event. No dose-limiting toxic effects were observed during the dose-escalation phase. 31 (34%; 95% CI 24–44) of 91 evaluable patients on camrelizumab monotherapy had an overall response with a median follow-up of 9·9 months (IQR 8·1–11·7). In the camrelizumab combination trial, between April 18, 2017, and Aug 15, 2017, 24 patients were assessed for eligibility, of whom 23 patients were enrolled and treated (safety population). 20 (87%) of 23 patients had grade 3 or 4 treatment-related adverse events: neutropenia (13 [57%] of 23 patients), anaemia (11 [48%] patients), leucopenia (11 [48%] patients), thrombocytopenia (seven [30%] patients), oedema (two [9%] patients), hyponatraemia (two [9%] patients), hypochloraemia (one [4%] patients), and rash (one [4%] patient). Two patients had treatment-related serious adverse events. No treatment-related deaths occurred in these trials. 20 (91% [95% CI 72–97]) of 22 evaluable patients had an overall response with a median follow-up time of 10·2 months (IQR 9·7–10·8).

Interpretation

Camrelizumab is a well tolerated, potential treatment option for patients with recurrent or metastatic nasopharyngeal carcinoma. The combination of camrelizumab plus gemcitabine and cisplatin has a manageable toxicity profile and promising preliminary antitumour activity for this disease in treatment-naive patients. Randomised controlled trials are needed to further establish the role of immune checkpoint inhibition for nasopharyngeal carcinomas.

Funding

Hengrui Medicine Co, Chinese National Natural Science Foundation project, Science and Technology Program of Guangdong, Pearl River Nova Program of Guangzhou.
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
Ava应助飞翔的企鹅采纳,获得10
14秒前
22秒前
量子星尘发布了新的文献求助10
29秒前
30秒前
noob_发布了新的文献求助20
31秒前
36秒前
43秒前
noob_完成签到,获得积分20
49秒前
echo发布了新的文献求助10
50秒前
founder发布了新的文献求助20
1分钟前
1分钟前
飞翔的企鹅完成签到,获得积分10
1分钟前
1分钟前
MchemG应助科研通管家采纳,获得10
1分钟前
MchemG应助科研通管家采纳,获得10
1分钟前
量子星尘发布了新的文献求助10
2分钟前
从容的水壶完成签到 ,获得积分10
2分钟前
量子星尘发布了新的文献求助10
3分钟前
George完成签到,获得积分10
3分钟前
4分钟前
wang完成签到,获得积分10
4分钟前
欣欣完成签到 ,获得积分10
4分钟前
柳行天完成签到 ,获得积分10
5分钟前
量子星尘发布了新的文献求助10
5分钟前
5分钟前
Djnsbj发布了新的文献求助10
6分钟前
sinan发布了新的文献求助10
6分钟前
WerWu完成签到,获得积分10
6分钟前
7分钟前
7分钟前
7分钟前
科研通AI2S应助科研通管家采纳,获得10
7分钟前
量子星尘发布了新的文献求助10
7分钟前
7分钟前
dara997发布了新的文献求助10
7分钟前
dara997完成签到,获得积分10
7分钟前
辣椒油完成签到,获得积分20
7分钟前
8分钟前
8分钟前
8分钟前
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 3976665
求助须知:如何正确求助?哪些是违规求助? 3520770
关于积分的说明 11204794
捐赠科研通 3257528
什么是DOI,文献DOI怎么找? 1798733
邀请新用户注册赠送积分活动 877897
科研通“疑难数据库(出版商)”最低求助积分说明 806629