【勘误】补漏ASCO ：TAB008 phase1(顺便看下其他几家)
东曜之前披露过90% CI的值，但是ASCO的摘要只有范围，这次更新
首先恭喜TOT BIOPHARM(东曜药业)，目前TAB008单抗联合紫杉醇和卡铂对比贝伐珠单抗(安维汀®)联合紫杉醇和卡铂化疗-线治疗晚期或复发性非鳞状细胞、非小细胞肺癌的III期临床研究正在招募进行中。
除了TAB008之外，汇总了ABP 215和HLX 04的1期，三个biosimilar和原研相比药物动力学均达到了生物等效性，且在免疫原性方面未观察到不同、安全性特征方面相似。
1 主要临床终点：几个PK数据的比较
ABP-215是目前唯一获批的Bevacizumab 的biosimilar (17年9月和11月分别被FDA和EMA批准)
HLX04是Helinus(复宏汉霖)开发的Bevacizumab的biosimilar，目前HLX04与贝伐珠单抗分别联合以奥沙利铂和5-氟尿嘧啶类为基础的化疗，治疗转移性结直肠癌疗效的III期试验正在招募中。
2 次要临床终点：安全性数据
首先是TAB008
下面是ABP215的AE统计
分组是这样
AE统计
5%以上的AE
HLX04的1b期数据（节选自某次会议Helinus CEO Dr. Scott Liu的PPT，本号无版权，此次纯属非商业引用）
3 原文
东曜的数据
A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of TAB008 and bevacizumab in healthy volunteers.
Citation: J Clin Oncol 36, 2018 (suppl; abstr e14504)
Author(s): Jacqueline M Liu, Xinghe Wang, Jin Wang, Lu Qi, Zejuan Wang, Xisheng Liu; TOT BIOPHARM, Suzhou, China; Capital Medical University and Peking University affiliated Beijing Shijitan Hospital, Beijing, China
Background: This study compared the pharmacokinetic (PK) profiles of the biosimilar TAB008 with bevacizumab (EU) in healthy adult males.
Methods: A randomized, double-blind, single-dose study in which healthy male subjects aged 18 to 45years, and body mass index 19-28kg/m2, were randomized to receive 1 mg/kg of TAB008 (n = 49) or bevacizumab (EU) (n = 50) over a 90 minute infusion. The subjects were followed for 99days after drug administration. Primary endpoints were area under the serum concentration–time curve from time 0 to time of last quantifiable concentration (AUC0-t), AUC from time 0 extrapolated to infinity (AUC0-inf), and the maximum observed serum concentration (Cmax). Secondary endpoints included safety and immunogenicity.
Results: The 2 groups of test subjects were well matched with regards to all demographic and baseline characteristics. The treatment-group ratios of LS geometric means for the 3 primary PK parameters were fully contained within the bioequivalence limits of 80.00% to 125.00% (90% CI: 103.66% to 118.33% for Cmax, 94.32% to 111.72% for AUC0-t, and 94.69% to 112.23% for AUC0-∞). Treatment-emergent adverse events (TEAEs) were reported in 25 (51.0%) subjects in the TAB008 group and 22 (44%) subjects in the Bevacizumab (EU) group; drug related TEAEs were reported in 19 (38%) subjects in both groups. NCI-CTCAE Grade 3 TEAEs were reported in 1 (2.0%) subject in the TAB008 group, and 3 (6.0%) subjects in the BevACIZUMAB(EU) group; there were no Grade 4 or 5 TEAEs. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies were detected in the TAB008 group, one subject in the bevacizumab (EU) group developed anti-drug antibody.
Conclusions: This study demonstrated the PK similarity of TAB008 to bevacizumab (EU). Safety and tolerability were comparable between treatments, and no subject developed binding or neutralizing anti-drug antibodies to TAB008.
Clinical trial information: CTR20160522.
ABP 215
A phase I, randomized, single-dose study evaluating the pharmacokinetic equivalence of biosimilar ABP 215 and bevacizumab in healthy adult men.
Markus R1, Chow V1, Pan Z1, Hanes V2
PURPOSE:
This study compared the pharmacokinetic (PK) profiles of the proposed biosimilar ABP 215 with bevacizumab in healthy males.
METHODS:
In this randomized, single-blind, single-dose, three-arm, parallel-group study, healthy subjects were randomized to receive ABP 215 (n = 68), bevacizumab (US) (n = 67), or bevacizumab (EU) (n = 67) 3 mg/kg intravenously. Primary endpoints were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed concentration (C max). Secondary endpoints included safety and immunogenicity.
RESULTS:
AUCinf and C max were similar across the three groups. Geometric means ratio (GMR) for C max and AUCinf, respectively, was 0.98 and 0.99 for ABP 215 versus bevacizumab (US); 1.03 and 0.96 for ABP 215 versus bevacizumab (EU); and 1.05 and 0.97 for bevacizumab (US) versus bevacizumab (EU). The 90% confidence intervals for the GMRs of AUCinf and C max were within the prespecified standard PK bioequivalence criteria of 0.80 to 1.25. The incidence of adverse events (AEs) was 47.1, 32.8, and 61.2% in the ABP 215, bevacizumab (US) and bevacizumab (EU) groups, respectively. When analyzed by investigational site, the incidence and severity of AEs were comparable in the ABP 215 and bevacizumab groups. There were no AEs leading to study discontinuation. No binding or neutralizing anti-drug anti-bodies was detected.
CONCLUSIONS:
This study demonstrated the PK similarity of ABP 215 to both bevacizumab (US) and bevacizumab (EU), and of bevacizumab (US) to bevacizumab (EU). Safety and tolerability were comparable between treatments and no subject developed binding or neutralizing anti-drug anti-bodies.