ABP 798 的疗效和安全性：JASMINE 试验中滤泡性淋巴瘤患者与利妥昔单抗参比制剂比较的结果。
Efficacy and Safety of ABP 798: Results from the JASMINE Trial in Patients with Follicular Lymphoma in Comparison with Rituximab Reference Product.
机构信息
Division of Hematology and Oncology, University of Leipzig, Liebigstr. 19, 04106, Leipzig, Germany.
Lithuanian University of Health Sciences, Kaunas, Lithuania.
出版信息
Target Oncol. 2020 Oct;15(5):599-611. doi: 10.1007/s11523-020-00748-4.
INTRODUCTION
ABP 798 is being developed as a biosimilar to rituximab reference product (RP), a CD20-directed cytolytic antibody that is approved in the US and EU for the treatment of non-Hodgkin lymphoma (NHL).
METHODS
This randomized, double-blind, comparative clinical study (JASMINE) evaluated the efficacy and safety of ABP 798 compared with rituximab RP. Adult, anti-CD20 treatment naïve patients diagnosed with grade 1, 2, or 3a follicular B-cell NHL expressing CD20 were randomized 1:1 to receive a 375 mg/m infusion of either ABP 798 or rituximab RP once weekly for 4 weeks and at weeks 12 and 20. Tumor assessments were performed at baseline and weeks 12 and 28. Primary endpoint was the risk difference (RD) of overall response rate (ORR) of complete response, unconfirmed complete response, or partial response by week 28 based on data from central, independent, and blinded assessments of disease.
RESULTS
Of the 256 randomized patients, 254 were treated with ABP 798 (n = 128; 100%) or rituximab RP (n = 126; 98.4%); 96 (78.0%) patients in the ABP 798 group and 87 (70.2%) in the rituximab RP group had a best ORR by week 28. The point estimate of RD in ORR between ABP 798 and rituximab RP from the adjusted generalized linear model for stratification factors was 7.7%. Clinical equivalence was based on sequential testing of the one-sided 95% lower confidence limits and one-sided 95% upper confidence limits of RD in ORR (- 1.4% and 16.8%, respectively) which was within the prespecified non-inferiority margin (- 15%) and non-superiority margin (35.5%), respectively. Results of sensitivity analyses were consistent with the primary efficacy analysis. ABP 798 was also comparable to rituximab RP across additional secondary endpoints, further supporting the conclusion of similarity, and including: RD of ORR at week 12; trough serum concentrations; percent of patients with complete depletion of CD19+ cell count at day 8; safety; and immunogenicity.
CONCLUSIONS
These results support a conclusion of similar clinical efficacy between ABP 798 and rituximab RP in patients with follicular lymphoma.
NCT NUMBER
NCT02747043; first posted April 21, 2016.
EUDRACT NUMBER
2013-005,542-11; submitted 14 October, 2014.
简介
ABP798 是一种利妥昔单抗参照产品（RP）的生物类似药，在美国和欧盟被批准用于治疗非霍奇金淋巴瘤（NHL）。
方法
这是一项随机、双盲、对照的临床研究（JASMINE），评估了 ABP798 与利妥昔单抗 RP 的疗效和安全性。年龄在 18 岁及以上、首次接受 CD20 治疗且患有 1 级、2 级或 3a 级滤泡性 B 细胞 NHL 并表达 CD20 的患者，按 1:1 比例随机接受每周一次的 ABP798 或利妥昔单抗 RP 375mg/m 输注，共 4 周，第 12 周和第 20 周再各输注一次。在基线和第 12 周及 28 周时进行肿瘤评估。主要终点是基于中央、独立和盲法评估疾病数据，28 周时总缓解率（ORR）的完全缓解、未确认完全缓解或部分缓解的风险差异（RD）。
结果
256 名随机患者中，254 名患者接受了 ABP798（n=128；100%）或利妥昔单抗 RP（n=126；98.4%）治疗；ABP798 组 96 名（78.0%）患者和利妥昔单抗 RP 组 87 名（70.2%）患者在第 28 周达到最佳 ORR。调整分层因素的广义线性模型的 RD 在 ORR 中的点估计值为 7.7%。基于 RD 在 ORR 中的单侧 95%置信下限和单侧 95%置信上限的连续检验，临床等效性为 RD（-1.4%和 16.8%）分别在预设的非劣效性界值（-15%）和非优越性界值（35.5%）内。敏感性分析的结果与主要疗效分析一致。ABP798 在其他次要终点方面也与利妥昔单抗 RP 相当，进一步支持了相似性的结论，包括：第 12 周的 ORR 差异；血清谷浓度；第 8 天 CD19+细胞计数完全耗竭的患者比例；安全性；和免疫原性。
结论
这些结果支持 ABP798 和利妥昔单抗 RP 在滤泡性淋巴瘤患者中的临床疗效相似。
NCT02747043；首次于 2016 年 4 月 21 日公布。
EUDRACT 编号：2013-005，542-11；于 2014 年 10 月 14 日提交。
Zotero 插件