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Abstract：
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.
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.
摘要：
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。
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。
