A First-in-Human, Phase 1, Multicenter, Open-label, Dose-Escalation Study of PCA062, an Antibody-Drug Conjugate Targeting P-Cadherin, in Patients with Solid Tumors.

结合 医学 药代动力学 药理学 化学 癌症 抗体-药物偶联物 癌症研究 临床研究阶段 药效学 内科学
作者
Matteo Duca,Darren W.T. Lim,Pete Anderson,Shunji Takahashi,John Sarantopoulos,Andrea Varga,Joseph Anthony D'Alessio,Tinya Abrams,Qing Sheng,Eugene Youchin Tan,Maria Santos Rosa,Juan Gonzalez-Maffe,Janna Sand-Dejmek,Claire Fabre,Miguel Martin
出处
期刊:Molecular Cancer Therapeutics [American Association for Cancer Research]
标识
DOI:10.1158/1535-7163.mct-21-0652
摘要

This first-in-human (FIH), phase 1, multicenter, open-label study was conducted to characterize the safety, tolerability, pharmacokinetics, and preliminary efficacy, and to establish the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) of PCA062 in patients with solid tumors. Adult patients with any solid tumor type and having a documented P-cadherin-positive tumor were enrolled; exceptions to P-cadherin positivity requirement were head and neck squamous cell carcinomas (HNSCC) and esophageal squamous cell carcinoma (ESCC). Dose escalation was guided by an adaptive Bayesian logistic regression model with escalation with overdose control to determine the MTD/RDE. Forty-seven patients were treated at 10 different dose levels of PCA062, ranging from 0.4 to 5.0 mg/kg Q2W administered as a 1-hour intravenous infusion. All enrolled patients discontinued the treatment; primary reason for discontinuation was progressive disease (78.7%). All 47 patients experienced at least one AE, of which 32 patients had a grade {greater than or equal to}3 AE and 37 patients experienced AEs suspected to be study drug related. The MTD of PCA062 was 3.6 mg/kg Q2W and thrombocytopenia was reported as a DLT that was attributed to the known toxicities of the DM1 payload with no P cadherin-related toxicities. PK was proportional, and no patients developed antidrug antibodies, suggesting adequate exposure at the doses tested. One patient out of 47 achieved a partial response and there was no correlation between tumor P-cadherin expression and clinical efficacy. Due to limited anti-tumor activity at the maximally tolerated dose level, Novartis has terminated clinical development of PCA062 (NCT02375958).
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
初初见你完成签到,获得积分10
4秒前
7秒前
思源应助淡淡月饼采纳,获得20
7秒前
dd完成签到 ,获得积分10
8秒前
Nayvue发布了新的文献求助10
12秒前
未来的幻想完成签到,获得积分10
14秒前
Kvolu29完成签到,获得积分10
15秒前
长理物电强完成签到,获得积分10
16秒前
若安在完成签到,获得积分10
17秒前
完美世界应助潘特采纳,获得10
18秒前
拼搏问薇完成签到 ,获得积分10
18秒前
单薄乐珍完成签到 ,获得积分0
21秒前
张静枝完成签到 ,获得积分10
21秒前
六步郎完成签到,获得积分10
21秒前
啊怙纲完成签到 ,获得积分10
23秒前
量子星尘发布了新的文献求助10
25秒前
scott_zip完成签到 ,获得积分10
26秒前
gxl完成签到,获得积分0
30秒前
xxx完成签到 ,获得积分10
33秒前
33秒前
努力生活的小柴完成签到,获得积分10
35秒前
37秒前
tangyong完成签到,获得积分10
39秒前
长安发布了新的文献求助10
39秒前
SucceedIn完成签到,获得积分10
40秒前
41秒前
44秒前
海洋岩土12138完成签到 ,获得积分10
45秒前
lzz完成签到 ,获得积分10
45秒前
冬雪完成签到,获得积分10
49秒前
woommoow完成签到,获得积分10
49秒前
aaatan完成签到 ,获得积分10
49秒前
lynn完成签到,获得积分10
50秒前
ABC发布了新的文献求助10
50秒前
回忆完成签到,获得积分10
51秒前
溜了溜了完成签到,获得积分10
54秒前
萧水白完成签到,获得积分10
56秒前
马桶盖盖子完成签到 ,获得积分10
56秒前
漆漆漆漆漆完成签到,获得积分10
58秒前
xzy998应助科研通管家采纳,获得10
58秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
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 4038184
求助须知:如何正确求助?哪些是违规求助? 3575908
关于积分的说明 11373872
捐赠科研通 3305715
什么是DOI,文献DOI怎么找? 1819255
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022