A phase III, randomized, double-blind, multicenter study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB8 (proposed bevacizumab biosimilar) and reference bevacizumab in patients with metastatic or recurrent nonsquamous non-small cell lung cancer
A phase III, randomized, double-blind, multicenter study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB8 (proposed bevacizumab biosimilar) and reference bevacizumab in patients with metastatic or recurrent nonsquamous non-small cell lung cancer
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DOI：
10.1016/j.lungcan.2020.05.027
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发表时间：
2020-08-01
期刊：
影响因子：
5.3
通讯作者：
Shin，Donghoon
中科院分区：
文献类型：
--
作者：
Reck，Martin;Luft，Alexander;Shin，Donghoon
目的比较生物相似候选药物SB8和参比产品贝伐单抗(BEV)治疗转移性或复发性非小细胞肺癌的有效性、安全性、药代动力学和免疫原性。方法患者随机(1：1)在III期双盲试验中接受SB8或BEV 15 /kg静脉滴注紫杉醇/卡铂，每3周一次，共24周，然后进行SB8或BEV维持治疗。主要终点是24周前的最佳总体应答率(ORR)。次要终点包括生存结果、安全性、PK和免疫原性。结果763例患者(SB8，n= 379；BEV，n= 384)被随机分配；基线特征平衡良好。Fas和PPS的最佳ORR分别为47.6%和42.8%，SB8和Bev的最佳ORR分别为50.1%和44.8%。最佳切缘比为1.11(90%CI，0.975−1.269)，最佳切缘比差异为5.3%(95%CI，−2.2%~12.9%)。无进展生存期分别为8.5个月和7.9个月(HR[95%CI]，0.99[0.83-1.18]；p= 0.9338)，总生存期分别为14.90个月和15.80个月(HR[95%CI]，1.03[0.83-1.28]；p= 0.7713)，有效时间分别为7.7个月和7.00个月(HR[95%CI]，1.05[0.81-1.37])；P= 0.6928)。SB8和BEV的严重程度和不良反应发生率、PK和免疫原性相似。结论SB8和BEV在最佳ORR风险比方面相当，具有相当的安全性、PK和免疫原性。
ObjectivesEfficacy, safety, pharmacokinetics (PK), and immunogenicity of the biosimilar candidate SB8 was compared to its reference product bevacizumab (BEV) in patients with metastatic or recurrent nonsquamous non―small cell lung cancer.MethodsPatients were randomized (1:1) in a phase III, double-blind study to receive intravenous SB8 or BEV 15 mg/kg with paclitaxel/carboplatin every 3 weeks for 24 weeks, followed by SB8 or BEV maintenance monotherapy. The primary endpoint was best overall response rate (ORR) by 24 weeks. Secondary endpoints included survival outcomes, safety, PK, and immunogenicity.Results763 patients (SB8,n= 379; BEV,n= 384) were randomized; baseline characteristics were well balanced. Best ORR in the FAS was 47.6% and 42.8%, and best ORR in the PPS was 50.1% and 44.8% for SB8 and BEV, respectively. The risk ratio of best ORR was 1.11 (90% CI, 0.975−1.269), and the risk difference in best ORR was 5.3% (95% CI, −2.2%–12.9%). Median survival outcomes were comparable between SB8 and BEV: progression-free survival was 8.50 vs 7.90 months, respectively (HR [95% CI], 0.99 [0.83–1.18];p= 0.9338); overall survival was 14.90 vs 15.80 months, respectively (HR [95% CI], 1.03 [0.83–1.28];p= 0.7713); and duration of response was 7.70 vs 7.00 months, respectively (HR [95% CI], 1.05 [0.81–1.37];p= 0.6928). Severity and incidence of treatment-emergent adverse events, PK, and immunogenicity were comparable between SB8 and BEV.ConclusionThis study demonstrated equivalence between SB8 and BEV in terms of best ORR risk ratio, with comparable safety, PK, and immunogenicity.