Socinski Mark A, Waller Cornelius F, Idris Tazeen, Bondarenko Igor, Luft Alexander, Beckmann Katrin, Vishweswaramurthy Ashwini, Loganathan Subramanian, Donnelly Charles, Hummel Matthew A, Shapiro Roxann, Woods Melody, Rao Anita, Nayak Vivek G, Ranganna Gopinath, Barve Abhijit
AdventHealth Cancer Institute, 2501 North Orange Avenue, Suite 289, Orlando, FL 32803, USA.
Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Centre Freiburg, Freiburg, Germany.
Ther Adv Med Oncol. 2021 Nov 18;13:17588359211045845. doi: 10.1177/17588359211045845. eCollection 2021.
This phase III study compared the efficacy and safety of proposed biosimilar MYL-1402O with reference bevacizumab (BEV), as first-line treatment for patients with stage IV non-squamous non-small-cell lung cancer.
Patients were randomly assigned (1:1) to receive MYL-1402O or bevacizumab with carboplatin-paclitaxel up to 18 weeks (6 cycles), followed by up to 24 weeks (8 cycles) of bevacizumab monotherapy. The primary objective was comparison of overall response rate (ORR), based on independently reviewed best tumor responses as assessed during the first 18 weeks. ORR was analyzed per US Food and Drug Administration (ratio of ORR) and European Medicines Agency (difference in ORRs) requirements for equivalence evaluation. Secondary end points included progression-free survival, disease control rate, duration of response, overall survival, safety, and immunogenicity over a period of 42 weeks, and pharmacokinetics (up to 18 weeks).
A total of 671 patients were included in the intent-to-treat population. The ratio of ORR was 0.96 [confidence interval (CI) 0.83, 1.12] and the difference in ORR was -1.6 (CI -9.0, 5.9) between treatment arms; CIs were within the predefined equivalence margins. Overall, the incidence of treatment-emergent adverse events and serious adverse events was comparable. Treatment-emergent anti-drug antibody (ADA) positivity was transient, with no notable differences between treatment arms (6.5% 4.8% ADA positivity rate in MYL-1402O BEV, respectively). The incidence of neutralizing antibody post-baseline was lower in the MYL-1402O arm (0.6%) compared to the bevacizumab arm (2.5%).
MYL-1402O is therapeutically equivalent to bevacizumab, based on the ORR analyses, with comparable secondary endpoints.
EU Clinical Trials Register, Registration # EudraCT no. 2015-005141-32https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005141-32.
Previous studies established bioequivalence of the proposed bevacizumab biosimilar MYL-1402O to reference bevacizumab. In this randomized, double-blind, phase III trial, MYL-1402O ( = 337) demonstrated comparable efficacy to bevacizumab ( = 334) in treating advanced non-squamous non-small-cell lung cancer per Food and Drug Administration and European Medicines Agency requirements for equivalence; the ratio of objective response rate (ORR) was 0.96 [90% confidence interval (CI) 0.83, 1.12] and the difference in ORR (MYL-1402O:bevacizumab) was -1.6 (95% CI -9.0, 5.9). Median progression-free survival at 42 weeks was comparable: 7.6 (7.0, 9.5) with MYL-1402O 9.0 (7.2, 9.7) months ( = 0.0906) with bevacizumab, by independent review. Treatment-emergent adverse events leading to death (2.4% vs 1.5%), serious adverse events (17.6% vs 16.7%), and antidrug antibodies (6.5% vs 4.8%), were comparable in the MYL-1402O vs bevacizumab arms, respectively. The incidence of neutralizing antibody post-baseline was lower with MYL-1402O (0.6%) than with bevacizumab (2.5%). These findings confirm therapeutic equivalence of MYL-1402O to bevacizumab, providing opportunities for improving access to bevacizumab.
本III期研究比较了拟用生物类似药MYL-1402O与参照药贝伐单抗（BEV）作为IV期非鳞状非小细胞肺癌患者一线治疗的疗效和安全性。
患者按1:1随机分配，接受MYL-1402O或贝伐单抗联合卡铂-紫杉醇治疗长达18周（6个周期），随后接受长达24周（8个周期）的贝伐单抗单药治疗。主要目标是比较总缓解率（ORR），基于在前18周期间独立评估的最佳肿瘤反应。根据美国食品药品监督管理局（ORR比值）和欧洲药品管理局（ORR差值）的等效性评估要求对ORR进行分析。次要终点包括42周期间的无进展生存期、疾病控制率、缓解持续时间、总生存期、安全性和免疫原性，以及药代动力学（长达18周）。
意向性治疗人群共纳入671例患者。治疗组间ORR比值为0.96[置信区间（CI）0.83, 1.12]，ORR差值为-1.6（CI -9.0, 5.9）；CI在预先定义的等效范围内。总体而言，治疗中出现的不良事件和严重不良事件的发生率相当。治疗中出现的抗药抗体（ADA）阳性是短暂的，治疗组间无显著差异（MYL-1402O和BEV的ADA阳性率分别为6.5%和4.8%）。与贝伐单抗组（2.5%）相比，MYL-1402O组基线后中和抗体的发生率较低（0.6%）。
基于ORR分析，MYL-1402O在治疗上等同于贝伐单抗，次要终点相当。
欧盟临床试验注册库，注册号EudraCT no. 2015-005141-32https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005141-32。
先前的研究确立了拟用的贝伐单抗生物类似药MYL-1402O与参照药贝伐单抗的生物等效性。在这项随机、双盲、III期试验中，根据美国食品药品监督管理局和欧洲药品管理局的等效性要求，MYL-1402O（n = 337）在治疗晚期非鳞状非小细胞肺癌方面显示出与贝伐单抗（n = 334）相当的疗效；客观缓解率（ORR）比值为0.96[90%置信区间（CI）0.83, 1.12]，ORR差值（MYL-1402O:贝伐单抗）为-1.6（95%CI -9.0, 5.9）。42周时的中位无进展生存期相当：经独立评估，MYL-1402O为7.6（7.0, 9.5）个月，贝伐单抗为9.0（7.2, 9.7）个月（P = 0.0906）。治疗中出现的导致死亡的不良事件（2.4%对1.5%）、严重不良事件（17.6%对16.7%）和抗药抗体（6.5%对4.8%）在MYL-1402O组和贝伐单抗组中分别相当。与贝伐单抗（2.5%）相比，MYL-1402O基线后中和抗体的发生率较低（0.6%）。这些发现证实了MYL-1402O与贝伐单抗的治疗等效性，为改善贝伐单抗的可及性提供了机会。
