贝伐单抗生物类似药SIBP04与贝伐单抗（阿瓦斯汀®）作为局部晚期或转移性非鳞状非小细胞肺癌一线治疗的疗效和安全性：一项随机、双盲、3期试验

IF 2.8

Cancer pathogenesis and therapy Pub Date : 2025-07-01 DOI:10.1016/j.cpt.2025.01.001

Yuankai Shi , Minghong Bi , Qingshan Li , Guolei Wang , Jianhua Chen , Mingjun Li , Jianhua Shi , Jiazhuan Mei , Yinghua Ji , Qingdi Xia , Yuanqing Feng , Shufeng Xu , Tongmei Zhang , Xiaohui Gao , Shubin Tang , Jie Weng , Zhuo Cao , Hongbo Wu , Xiubao Ren , Hua Xie , Sheng Yang

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引用次数: 0

摘要

sibp04是贝伐单抗（Avastin®，Roche, Basel, Switzerland）的生物仿制药。本研究评估了SIBP04与Avastin®作为局部晚期或转移性非鳞状非小细胞肺癌（nsqNSCLC）一线治疗的等效性。在这项随机、双盲、多中心、3期试验中，我们招募了来自中国58家医院的局部晚期或转移性nsqNSCLC患者。患者按1:1随机分配，接受SIBP04或Avastin®（15 mg/kg）联合紫杉醇（175 mg/m2）和卡铂（曲线下面积[AUC] = 5.0，不超过800 mg）（PC）静脉注射方案（3周周期，最多6个周期），随后接受SIBP04维持治疗。主要终点是客观缓解率（ORR），定义为从第一次给药到第18周的最佳总体缓解，由独立审查委员会（IRC）根据实体瘤反应评估标准（RECIST） 1.1版评估。主要终点的临床等效性是通过比较每个方案集（PPS）人群中ORR比率（SIBP04 + PC vs. Avastin®+ PC）的双侧90%置信区间（CI）来实现的，其预先规定的等效范围为0.75-1.33。次要终点包括无进展生存期、总生存期、反应持续时间、疾病控制率、安全性、免疫原性和稳态谷浓度的药理学生物等效性。结果从2020年4月17日至2021年4月20日，517例患者随机分配接受SIBP04 + PC （n = 259）或Avastin®+ PC （n = 258）治疗。在全分析集（FAS）人群中，SIBP04 + PC组的ORR为55.6% (95% CI, 49.3-61.8)， Avastin + PC组的ORR为59.3% (95% CI, 53.0-65.4) (P = 0。3944)。SIBP04 + PC组在PPS人群中的ORR为62.6% (95% CI, 55.8-69.0)， Avastin + PC组的ORR为64.7% (95% CI, 58.0-71.0) （P = 0.6448）。FAS人群的ORR比（SIBP04 + PC vs. Avastin®+ PC）分别为0.94 （90% CI, 0.8270-1.0621）和0.97 (90% CI, 0.8578-1.0900)，均在预定的0.75-1.33等效范围内。其他疗效终点、安全性、免疫原性和药代动力学在各组间均具有可比性。结论sibp04在局部晚期或转移性nsqNSCLC患者中具有与阿瓦斯汀相同的疗效和安全性。SIBP04 + PC方案将为这类患者提供另一种一线治疗选择。临床试验注册：clinicaltrials .gov，标识符NCT05318443。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Efficacy and safety of bevacizumab biosimilar SIBP04 compared with bevacizumab (Avastin®) as first-line treatment for locally advanced or metastatic non-squamous non-small-cell lung cancer: A randomized, double-blind, phase 3 trial

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Background

SIBP04 is a biosimilar of bevacizumab (Avastin®, Roche, Basel, Switzerland). This study evaluated the equivalence of SIBP04 to Avastin® as first-line treatment for locally advanced or metastatic non-squamous non-small-cell lung cancer (nsqNSCLC).

Methods

In this randomized, double-blind, multi-center, phase 3 trial, we recruited patients with locally advanced or metastatic nsqNSCLC from 58 hospitals at China. Patients were randomly allocated 1:1 to receive SIBP04 or Avastin® (15 mg/kg) combined with paclitaxel (175 mg/m²) and carboplatin (area under curve [AUC] = 5.0, no more than 800 mg) (PC) regimens intravenously (3-week cycles, up to six cycles) followed by SIBP04 maintenance therapy. The primary endpoint was objective response rate (ORR), defined as the best overall response from the first dose to the 18th week, assessed by the independent review committee (IRC) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Clinical equivalence of the primary endpoint was done by comparing the two-sided 90% confidence interval (CI) of the ORR ratio (SIBP04 plus PC vs. Avastin® plus PC) in the per-protocol set (PPS) populaiton with the prespecified equivalence margin of 0.75–1.33. Secondary endpoints included progression-free survival, overall survival, duration of response, disease control rate, safety, immunogenicity, and pharmacological bioequivalence of steady-state trough concentrations.

Results

From April 17, 2020, to April 20, 2021, 517 patients were randomly assigned to receive SIBP04 plus PC (n = 259) or Avastin® plus PC (n = 258). The ORR of the SIBP04 plus PC group was 55.6% (95% CI, 49.3–61.8) and that of the Avastin® plus PC group was 59.3% (95% CI, 53.0–65.4) in the full analysis set (FAS) population (P = 0. 3944). The ORR of the SIBP04 plus PC group was 62.6% (95% CI, 55.8–69.0) and that of the Avastin® plus PC group was 64.7% (95% CI, 58.0–71.0) in the PPS population (P = 0.6448). The ORR ratio (SIBP04 plus PC vs. Avastin® plus PC) was 0.94 (90% CI, 0.8270–1.0621) in the FAS population and 0.97 (90% CI, 0.8578–1.0900) in the PPS population, respectively, both within the prespecified equivalence margin of 0.75–1.33. Other efficacy endpoints, safety, immunogenicity, and pharmacokinetics were all comparable across the groups.

Conclusions

SIBP04 showed equivalent efficacy and safety profile to Avastin® in patients with locally advanced or metastatic nsqNSCLC. SIBP04 plus PC regimen will offer an alternative first-line treatment option for this patient population.