Population Pharmacokinetics and Exposure–Response Analysis of Tremelimumab 300 mg Single Dose Combined with Durvalumab 1500 mg Q4W (STRIDE) in Patients with Unresectable Hepatocellular Carcinoma

银耳霉素 杜瓦卢马布 医学 人口 肿瘤科 内科学 药代动力学 肝细胞癌 癌症 环境卫生 免疫疗法 无容量 易普利姆玛
作者
KyoungSoo Lim,Aburough Abegesah,Chunling Fan,Zhijian He,Xuyang Song,Cecil Chen,Alejandra Negro,M. Makowsky,Charu Gupta,Song Ren,Alex Phipps,Megan Gibbs,Diansong Zhou
出处
期刊:The Journal of Clinical Pharmacology [Wiley]
卷期号:63 (11): 1221-1231 被引量:1
标识
DOI:10.1002/jcph.2288
摘要

A novel single-dose regimen of 300 mg tremelimumab in combination with durvalumab (STRIDE) has demonstrated a favorable benefit-risk profile in the phase 1/2 Study 22 trial (in patients with unresectable hepatocellular carcinoma, uHCC) and in the phase 3 HIMALAYA study. The current analysis evaluated the population pharmacokinetics (PopPK) of tremelimumab and durvalumab, and the exposure-response (ER) relationship for efficacy and safety of STRIDE in patients with uHCC. Previous PopPK models for tremelimumab and durvalumab were updated using data from previous studies in various cancers combined with data from Study 22 and HIMALAYA. Typical population mean parameters and associated inter- and intra-individual variability were assessed, as was the influence of covariates. Individual exposure metrics were derived from the individual empirical Bayes estimates as drivers for ER analysis related to efficacy and safety from HIMALAYA. The observed pharmacokinetics of tremelimumab in uHCC were well described by a 2-compartment model with both linear and time-dependent clearance. All identified covariates changed tremelimumab PK parameters by <25%, and thus had minimal clinical relevance; similar results were obtained from durvalumab PopPK analysis. None of tremelimumab or durvalumab exposure metrics were significantly associated with overall survival (OS), progression-free survival (PFS), or adverse events. Baseline aspartate aminotransferase and neutrophil-to-lymphocyte ratio (NLR) were associated with OS (P < .001) by the Cox proportional hazards model. No covariate was identified as a significant factor for PFS. No dose adjustment for tremelimumab or durvalumab is needed based on PopPK covariate analyses or ER analyses. Our findings support the novel STRIDE dosing regimen in patients with uHCC.
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
tangyong完成签到,获得积分10
刚刚
tananna完成签到,获得积分10
1秒前
1秒前
傻傻的咖啡豆完成签到,获得积分10
2秒前
哦吼发布了新的文献求助10
2秒前
度帕明发布了新的文献求助10
2秒前
谜呀发布了新的文献求助10
3秒前
李爱国应助陆未离采纳,获得30
3秒前
丘比特应助高兴的万声采纳,获得10
3秒前
yanmh完成签到,获得积分10
4秒前
李小伟完成签到,获得积分10
4秒前
Senna完成签到,获得积分10
5秒前
5秒前
落寞冬云完成签到,获得积分10
5秒前
5秒前
踏月偷心发布了新的文献求助10
6秒前
Prozac完成签到,获得积分10
6秒前
wisdom完成签到,获得积分0
6秒前
7秒前
满意的醉蝶完成签到,获得积分10
8秒前
度帕明完成签到,获得积分10
8秒前
尤寄风发布了新的文献求助10
8秒前
qq完成签到 ,获得积分10
8秒前
今后应助qidada采纳,获得10
9秒前
小情绪完成签到 ,获得积分10
9秒前
景代丝完成签到,获得积分10
9秒前
冷傲天川发布了新的文献求助10
9秒前
九三完成签到,获得积分10
9秒前
Swu完成签到,获得积分10
9秒前
9秒前
Weining完成签到,获得积分10
10秒前
钰宁完成签到,获得积分10
10秒前
如意竺完成签到,获得积分10
10秒前
全职法师刘海柱完成签到,获得积分10
11秒前
飞翔的梦完成签到,获得积分10
11秒前
Vivian完成签到,获得积分10
11秒前
11秒前
老衲完成签到,获得积分0
12秒前
可乐不加冰完成签到,获得积分10
12秒前
王大可完成签到,获得积分10
13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
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 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 3968608
求助须知:如何正确求助?哪些是违规求助? 3513486
关于积分的说明 11168243
捐赠科研通 3248926
什么是DOI,文献DOI怎么找? 1794540
邀请新用户注册赠送积分活动 875188
科研通“疑难数据库(出版商)”最低求助积分说明 804676