CHMP recommends EU approval of Roche’s Tecentriq plus Abraxane for metastatic TNBC

罗氏PD-L1抗体Tecentriq获得欧盟推荐批准用于联合治疗三阴性乳腺癌

2019-07-02 17:02:00 PHARMACEUTICAL

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Roche announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of Tecentriq (atezolizumab) plus chemotherapy (Abraxane; nab-paclitaxel) for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumours have PD-L1 expression (≥ 1%) and who have not received prior chemotherapy for metastatic disease. “This CHMP recommendation marks a breakthrough in the treatment of triple-negative breast cancer, an aggressive type of breast cancer with high unmet medical need,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “With today’s announcement, we hope that people living with PD-L1-positive metastatic triple-negative breast cancer in Europe will soon have a new treatment option with the Tecentriq combination.” The CHMP recommendation is based on data from the Phase III IMpassion130 study, which demonstrated that Tecentriq plus nab-paclitaxel significantly reduced the risk of disease worsening or death (progression-free survival; PFS) by 38% compared with nab-paclitaxel alone (median PFS=7.5 vs 5 months; HR=0.62, 95% CI: 0.49–0.78, p<0.0001) in people who were tested positive for PD-L1 expression on tumour-infiltrating immune cells (IC). The Tecentriq combination showed a clinically meaningful overall survival (OS) improvement of seven months vs nab-paclitaxel alone in the PD-L1-positive population (median OS=25.0 vs 18.0 months; HR=0.71, 95% CI: 0.54–0.93). OS results in the PD-L1-positive population were not formally tested due to the hierarchical design of the study, as statistical significance was not met for OS in the intention-to-treat (ITT) population (median OS=21.0 vs 18.7 months; HR=0.86, 95% CI: 0.72–1.02, p=0.078). The study will continue until the next planned analysis. The assessment of PD-L1 on tumour-infiltrating immune cells is essential for identifying the TNBC patients benefiting from this Tecentriq combination. PD-L1 expression status in the IMpassion130 study was assessed by the VENTANA PD-L1 (SP142) assay. Safety in the Tecentriq plus nab-paclitaxel arm appeared consistent with the known safety profiles of the individual study medicines or underlying disease, and no new safety signals were identified with the combination. Serious adverse events (SAEs) were reported in 23% of people receiving Tecentriq plus nab-paclitaxel, compared with 18% of people receiving chemotherapy alone. Grade 3–4 AEs were reported in 49% of people receiving Tecentriq plus nab-paclitaxel, compared with 42% of people receiving chemotherapy alone. Currently, Roche has seven ongoing Phase III studies investigating Tecentriq in TNBC, including early and advanced stages of the disease. IMpassion130 is a Phase III, multicentre, randomised, double-blind study evaluating the efficacy, safety and pharmacokinetics of Tecentriq plus nab-paclitaxel compared with placebo plus nab-paclitaxel in people with unresectable locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic breast cancer. The study enrolled 902 people who were randomised equally (1:1) The co-primary endpoints are PFS per investigator assessment (RECIST 1.1) in the ITT population and in the PD-L1-positive population, and OS in the ITT population and in the PD-L1-positive population. Performing a test for statistical significance for OS in the PD-L1-positive population is dependent upon OS results from all randomised patients. PD-L1 expression status was assessed by the VENTANA PD-L1 (SP142) Assay. Secondary endpoints include objective response rate and duration of response. Breast cancer is the most common cancer among women, with more than 2 million diagnosed worldwide each year.1 TNBC represents 15% of all breast cancers and is more common in women under the age of 50, compared with other forms of breast cancer.2,3,4 It is defined by the lack of expression and/or amplification of the targetable receptors for oestrogen, progesterone and HER2 amplification.5 Patients with metastatic TNBC generally experience rapid progression and shorter OS, compared with other subtypes of breast cancer. Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T cells. Tecentriq is a cancer immunotherapy (CIT) that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively. Tecentriq is approved in the US, EU and/or countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer, and in PD-L1-positive triple-negative breast cancer.
罗氏宣布,欧洲药物管理局(EMA)人类用药委员会(CHMP)已建议批准Tecentriq (atezolizumab)联合化疗(Abraxane;nab-紫杉醇)用于治疗无法切除的局部晚期或转移性三阴性乳腺癌(TNBC)的成年患者,其肿瘤具有PD-L1表达(1%),且此前未接受转移性疾病的化疗。 罗氏(Roche)首席医疗官兼全球产品开发总监桑德拉•霍宁( Sandra Horning )表示:“ CHMP 建议标志着治疗三重阴性乳腺癌取得了突破,这是一种积极的、医疗需求未得到满足的乳腺癌类型。”“在今天的声明中,我们希望欧洲患有 PD-L1阳性转移性三阴性乳腺癌的人很快就会有一个新的治疗选择,结合 Tecentriq 。” CHMP 推荐基于 III 期 IMobion130研究的数据,该研究表明 Tecentriq 和 nab-paclitaxel 相比单独使用 nab-paclitaxel 可显著降低疾病恶化或死亡(无进展生存期; PFS )的风险38%(中位 PFS =7.5 vs 5个月; HR =0.62,95% CI :0.49–0.78)。p <0.0001)在肿瘤浸润免疫细胞( IC )上检测 PD-L1表达阳性的患者中。 在 PD-L1阳性人群中, Tecentriq 联合应用显示,在临床上有意义的总生存期( OS )提高了7个月,而仅 nab-paclite (中位数 OS =25.0 vs 18.0个月; HR =0.71,95% CI :0.54–0.93)。由于研究的分层设计,未对 PD-L1阳性人群的 OS 结果进行正式测试,因为意向治疗( ITT )人群中的 OS 没有达到统计学显著性(中位数 OS =21.0 vs 18.7个月; HR =0.86,95% CI :0.72-1.02, p =0.078)。这项研究将持续到下一次计划的分析。 评估 PD-L1对肿瘤浸润免疫细胞至关重要,以确定 TNBC 患者受益于这一技术组合。采用 VENTANNA PD-L1( SP142)法评估了 PD-L1在 IM激情130研究中的表达状况。 Tecentriq + nab-paclitaxel 臂的安全性似乎与已知的个别研究药物或潜在疾病的安全性概况一致,并且没有发现新的安全信号与组合。在接受 Tecentriq + nab-paclitaxel 治疗的患者中,有23%报告严重不良事件( SAEs ),而仅接受化疗的患者中只有18%。 在接受 Tecentriq + nab-paclitaxel 治疗的患者中,有49%的人出现了3-4级 AE ,而仅接受化疗的人中,这一比例为42%。 目前,罗氏(Roche)公司有七项正在进行的 III 期研究在 TNBC 的 Tecentriq ,包括早期和晚期的疾病。 IMobion130是一项 III 期、多中心、随机、双盲研究,评估 Tecentriq + nab-paclitaxel 与安慰剂+ nab-paclitaxel 相比的疗效、安全性和药代动力学,这些患者的局部晚期或转移性 TNBC 是无法切除的,他们尚未接受转移性乳腺癌的系统治疗。 这项研究对902人进行了同样随机的研究(1:1),共同的主要终点是 ITT 人群和 PD-L1阳性人群中的 PFS ( RECIST 1.1),以及 ITT 人群和 PD-L1阳性人群中的 OS 。 对 PD-L1阳性人群的 OS 进行统计学显著性的测试取决于所有随机患者的 OS 结果。用 VENTTANA PD-L1( SP142)法检测 PD-L1表达状况。次要终点包括客观反应率和反应持续时间。 乳腺癌是女性最常见的癌症,每年全世界有200多万人被确诊。1 TNBC 占所有乳腺癌的15%,50岁以下的妇女比其他形式的乳腺癌更为常见。2,3,4它的定义是雌激素、孕激素和 HER2扩增的目标受体缺乏表达和/或扩增。与其他乳腺癌亚型相比,转移性肿瘤坏死因子( TNBC )患者一般经历快速进展和较短的 OS 。 Tecentriq 是一种单克隆抗体,旨在与一种名为 PD-L1的蛋白结合,这种蛋白表达于肿瘤细胞和肿瘤浸润的免疫细胞,阻断其与 PD-1和 B7.1受体的相互作用。通过抑制 PD-L1, Tecentriq 可以激活 T 细胞。 Tecentriq 是一种癌症免疫疗法( CIT ),它有可能与其他免疫疗法、靶向药物和各种癌症化疗联合使用。Tecentriq 及其临床项目的开发基于我们对免疫系统如何与肿瘤相互作用以及如何更有效地利用人的免疫系统对抗癌症的更多理解。 Tecentriq 在美国、欧盟和/或世界各国获得批准,无论是单独或与靶向治疗和/或化疗联合应用于各种形式的非小细胞和小细胞肺癌、某些类型的转移性尿路上皮癌,以及 PD-L1阳性的三重阴性乳腺癌。

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