目的:曲妥珠单抗靶向人表皮生长因子受体2(HER2)受体,用于治疗HER2阳性转移性乳腺癌。BP02,一种重组IgG1κ人源化单克隆抗体,正在开发为曲妥珠单抗生物仿制药。这项研究的目的是评估BP02与参考曲妥珠单抗(RT:Herceptin®-EU)在HER2阳性转移性乳腺癌患者中的等效性。
方法:这种双盲,1:1随机化,平行组,主动控制,III期等效性试验招募了18-75岁组织学/细胞学证实为HER2阳性的女性,局部复发或转移性乳腺癌伴全身转移,来自印度的59个地点。患者按雌激素受体/孕激素受体状态进行1:1分层,接受BP02/RT(第1周期第1天的8-mg/kg负荷剂量,第1周期第2-8天的6mg/kg,每个3周周期)联合多西他赛(第1周期第1-8天的75mg/m2)[诱导期]。有完全或部分反应的参与者,在诱导期结束时或稳定的疾病继续研究药物直到疾病进展/治疗停止[维持期]。主要疗效终点是实体瘤中每个反应评估标准的客观反应率(RECIST)1.1。
结果:9月23日之间,2020年9月16日,2022年,招募了690名患者(BP02/RT各345名)。在诱导阶段结束时(意向治疗人群),相似比例的患者获得BP02的客观缓解率(n=231[67.0%],95%置信区间[CI]62.0,71.9)和RT(n=238[69.0%],95%CI64.1,73.9)。风险差异的95%CI(-2.03,95%CI-9.15,5.09)和90%CI风险比(0.97,90%CI0.89,1.06)在±13%和(0.80,1.25)的等效范围内,分别。据报道,出现治疗引起的不良事件导致治疗退出的患者分别为2.9%和3.2%的BP02和RT患者,分别。
结论:BP02在24周结束时表现出与RT相当的疗效和相似的安全性。
背景:CTRI编号:CTRI/2020/04/024456。
OBJECTIVE: Trastuzumab targets human epidermal growth factor receptor 2 (HER2) receptors and is indicated for treating HER2-positive metastatic breast cancer. BP02, a recombinant IgG1 kappa humanized monoclonal antibody, is being developed as a
trastuzumab biosimilar. The objective of this
study was to evaluate the equivalence of BP02 with reference
trastuzumab (RT: Herceptin®-EU) in patients with HER2-positive metastatic breast cancer.
METHODS: This double-blinded, 1:1 randomized, parallel-group, active-controlled, phase III equivalence
trial recruited women aged 18-75 years with histologically/cytologically confirmed HER2- positive, locally recurrent or metastatic breast cancer with systemic metastasis, from 59 sites in India. Patients were randomly allocated 1:1 stratified by estrogen receptor/progesterone receptor status to receive BP02/RT (8-mg/kg loading dose on day 1-cycle 1, 6 mg/kg on day 1-cycles 2-8, of each 3-week cycle) combined with docetaxel (75 mg/m2 on day 1-cycles 1-8) [induction phase]. Participants with complete or partial response, or stable disease at the end of the induction phase continued the
study drug until disease progression/treatment discontinuation [maintenance phase]. The primary efficacy endpoint was the objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
RESULTS: Between 23 September, 2020 and 16 September, 2022, 690 patients were recruited (n = 345 each to BP02/RT). At the end of the induction phase (intent-to-treat population), a similar proportion of patients achieved an objective response rate with BP02 (n = 231 [67.0%], 95% confidence interval [CI] 62.0, 71.9) and RT (n = 238 [69.0%], 95% CI 64.1, 73.9). The 95% CI of risk difference (-2.03, 95% CI -9.15, 5.09) and 90% CI of risk ratio (0.97, 90% CI 0.89, 1.06) were within equivalence margins of ± 13% and (0.80, 1.25), respectively. Treatment-emergent adverse events leading to treatment withdrawal were reported in 2.9% and 3.2% patients with BP02 and RT, respectively.
CONCLUSIONS: BP02 showed an equivalent efficacy and similar safety profile to RT at the end of 24 weeks.
BACKGROUND: CTRI Number: CTRI/2020/04/024456.