Servier today announced that Blood Advances published long-term data from the Phase 3 AGILE trial evaluating TIBSOVO (ivosidenib) in combination with azacitidine versus placebo-azacitidine in patients with newly diagnosed mutant isocitrate dehydrogenase 1 (mIDH1) acute myeloid leukemia (AML) who were unfit to receive intensive chemotherapy. The post-hoc analysis reports positive long-term follow-up results from the pivotal Phase 3 AGILE trial and continues to demonstrate the sustained survival benefit reported in the previous analysis published in the New England Journal of Medicine (NEJM).®

施维雅今天宣布，Blood Advances 公布了 3 期 AGILE 试验的长期数据，该试验评估了 TIBSOVO（伊伏西尼）联合阿扎胞苷与安慰剂阿扎胞苷治疗新诊断的突变异柠檬酸脱氢酶 1 （mIDH1） 急性髓系白血病 （AML） 患者不适合接受强化化疗。事后分析报告了关键的 3 期 AGILE 试验的积极长期随访结果，并继续证明之前发表在《新英格兰医学杂志》（NEJM） 上的分析中报告的持续生存获益。

'The clear and robust clinical benefit demonstrated by these long-term analyses – including prolonged overall survival and hematologic recovery – support TIBSOVO as a standard of care treatment for patients with IDH1-mutated AML,' said

“这些长期分析显示的明确而强劲的临床益处——包括延长总体生存期和血液学恢复——支持TIBSOVO作为IDH1突变型AML患者的护理标准治疗，”

Susan Pandya

苏珊·潘迪亚

, M.D., Vice President Clinical Development and Global Head of Oncology LS/LCM, Servier. 'These data are a testament to Servier's industry-leading research in IDH1-mutated cancers, including AML, and demonstrate our steadfast commitment to improving outcomes for patients.'

医学博士，临床开发副总裁兼肿瘤学LS/LCM全球主管，施维雅公司。'这些数据证明了施维雅在IDH1突变癌症（包括急性髓系白血病）领域的行业领先研究，并展示了我们改善患者预后的坚定承诺。'

As of data cutoff in

截至数据截止时

June 2022

2022年6月

, median follow-up was 28.6 months. Key findings from the newly published analysis include:

，中位随访时间为28.6个月。新发表的分析的主要发现包括：

Median overall survival (OS) was significantly longer in patients treated with the TIBSOVO combination (29.3 months; 95% CI, 13.2 - not reached) than placebo-azacitidine (7.9 months; 95% CI, 4.1-11.3; hazard ration [HR]=0.42 [0.27, 0.65]; p<.0001).

接受TIBSOVO联合治疗的患者中位总生存期（OS）显著长于接受安慰剂加阿扎胞苷的患者（29.3个月；95%置信区间，13.2-未达到 vs 7.9个月；95%置信区间，4.1-11.3；风险比 [HR]=0.42 [0.27, 0.65]；p<0.0001）。

Hematologic recovery was generally faster and lasted longer in patients in the TIBSOVO arm compared to placebo-azacitidine. Conversion to transfusion independence was more common with TIBSOVO (53.8%) than placebo-azacitidine (17.1%; p=.0004).

与安慰剂-阿扎胞苷相比，TIBSOVO组患者的血液学恢复通常更快且持续时间更长。TIBSOVO（53.8%）比安慰剂-阿扎胞苷（17.1%；p=.0004）转变为无需输血的情况更为常见。

Ten (30.3%) of the 33 molecular measurable-residual disease (MRD)-evaluable patients in the TIBSOVO arm converted to an MRD-negative response by Day 1 of Cycle 14, all of whom had a complete response (CR). Seven (70%) of these patients converted to an MRD-negative response by Day 1 of Cycle 7. Of the 23 patients who remained MRD-positive, 19 had a CR and four had a CR with incomplete hematologic recovery (CRi).

在TIBSOVO组中，33名可进行分子学可测量残留病（MRD）评估的患者中有10名（30.3%）在第14周期第1天转为MRD阴性反应，这些患者全部达到了完全缓解（CR）。其中7名（70%）患者在第7周期第1天转为MRD阴性反应。在仍然保持MRD阳性的23名患者中，19名患者达到CR，4名患者达到伴有不完全血液学恢复的完全缓解（CRi）。

Two patients (20%) had an MRD-negative response in the placebo-azacitidine arm..

在安慰剂-阿扎胞苷组中，两名患者（20%）达到了MRD阴性反应。

The long-term safety profile of TIBSOVO with azacitidine was consistent with previously reported data. The most commonly reported Grade ≥3 hematologic adverse events (AEs) were anemia (26.4%), neutropenia (30.6%), and febrile neutropenia (27.8%). The most common Grade ≥3 nonhematologic AEs were electrocardiogram QT prolonged (11.1%), pneumonia (22.2%), nausea, (2.8%), hypokalemia (2.8%), and pyrexia (2.8%).

TIBSOVO与阿扎胞苷的长期安全性特征与之前报告的数据一致。最常见的3级或以上血液学不良事件（AEs）为贫血（26.4%）、中性粒细胞减少（30.6%）和发热性中性粒细胞减少（27.8%）。最常见的3级或以上非血液学不良事件为心电图QT间期延长（11.1%）、肺炎（22.2%）、恶心（2.8%）、低钾血症（2.8%）和发热（2.8%）。

There were no new or unexpected safety signals or additional treatment discontinuations due to AEs compared with the primary analysis..

与初步分析相比，没有出现新的或意外的安全信号，也没有因不良事件导致额外的治疗中断。

'Long-term results from the AGILE trial underscore the power of TIBSOVO to improve outcomes for patients with IDH1-mutated AML unfit for intensive chemotherapy, a group who historically has had a poor long-term prognosis,' said Hartmut Döhner, MD, Professor of Medicine and Director of the Department of Internal Medicine III at the University Hospital Ulm in .

“AGILE试验的长期结果强调了TIBSOVO在改善不适合接受高强度化疗的IDH1突变型AML患者预后方面的强大作用，这类患者历史上长期预后较差，”乌尔姆大学医院内科主任、医学教授哈特穆特·多纳博士表示。

Germany

德国

and Director of the National Center for Tumor Diseases SouthWest (NCT-SW; Ulm site). 'These results continue to emphasize the importance of early systematic genetic testing to guide treatment selection for patients – which may lead to improved overall survival rates and a reduction in the risk of death as seen in this study.'.

国家西南部肿瘤疾病中心（NCT-SW；乌尔姆分部）主任表示：“这些结果继续强调了早期系统性基因检测在指导患者治疗选择方面的重要性——这可能会提高总体生存率，并降低本研究中所见的死亡风险。”

TIBSOVO was

TIBSOVO是

approved

已批准

by the U.S. Food and Drug Administration (FDA) in combination with azacitidine for the treatment of patients with newly diagnosed IDH1-mutated AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy, in

美国食品药品监督管理局（FDA）批准与阿扎胞苷联合使用，用于治疗新诊断的IDH1突变型急性髓系白血病（AML）的成年患者，适用于75岁及以上或存在合并症而无法使用高强度诱导化疗的患者，

May 2022

2022年5月

under Priority Review. The supplemental New Drug Application (sNDA) for TIBSOVO was reviewed by the FDA under its Real-Time Oncology Review (RTOR) pilot program, which aims to ensure that safe and effective treatments are available to patients as early as possible.

在优先审查下。TIBSOVO的补充新药申请（sNDA）通过FDA的实时肿瘤审评（RTOR）试点项目进行审查，该项目旨在确保安全有效的治疗能够尽早提供给患者。

About Servier Pharmaceuticals in the U.S.

关于施维雅制药在美国的情况

As the U.S. affiliate of the Servier Group, Servier Pharmaceuticals is focused on delivering transformative oncology and neurology medicines that fill a critical need for patients who are underserved by current therapies.

作为施维雅集团的美国分公司，施维雅制药专注于提供满足当前疗法未能充分满足患者需求的关键性肿瘤学和神经学药物。

Since opening its headquarters in

自从开设总部以来

Boston

波士顿

, U.S., in 2018, Servier Pharmaceuticals quickly became a leader in cancer care and is taking bold steps to build a powerful portfolio of precision therapeutics for patients living with cancer and neurological conditions.

美国，2018年，施维雅制药公司迅速成为癌症治疗领域的领导者，并正在采取大胆的步骤，为患有癌症和神经系统疾病的患者构建强大的精准治疗产品组合。

Governed by a non-profit foundation, Servier Group's private corporate governance enables the company to combine its resources and global network with cutting-edge science and creativity to develop tailored solutions that drive meaningful progress for patients.

由非营利基金会管理，施维雅集团的私人企业治理使公司能够将其资源和全球网络与前沿科学和创造力相结合，开发出推动患者有意义进展的定制解决方案。

Servier is actively seeking alliances, partnerships and acquisitions across all stages of oncology and neurology research and development to accelerate the delivery of innovative treatments to patients as part of its trailblazing

施维雅正在积极寻求在肿瘤学和神经学研究与开发的各个阶段建立联盟、合作伙伴关系和进行收购，以加速向患者提供创新治疗方案，作为其开拓性努力的一部分。

About the AGILE Phase 3 AML Trial (NCT03173248)

关于AGILE第三阶段AML试验（NCT03173248）

The AGILE trial is a global, Phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial designed to evaluate the efficacy and safety of TIBSOVO in combination with azacitidine compared with placebo in combination with azacitidine, in adults with previously untreated IDH1-mutated acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy (≥75 years old or who have comorbidities that preclude the use of intensive induction chemotherapy).

AGILE 试验是一项全球性、III 期、多中心、双盲、随机、安慰剂对照的临床试验，旨在评估 TIBSOVO 联合阿扎胞苷相较于安慰剂联合阿扎胞苷在未接受过治疗的 IDH1 突变急性髓系白血病（AML）成人患者中的疗效和安全性，这些患者不适合接受高强度化疗（≥75 岁或因合并症无法使用高强度诱导化疗）。

The study's primary endpoint is event-free survival (EFS), defined as the time from randomization until treatment failure, relapse from remission, or death from any cause, whichever occurs first. Treatment failure is defined as failure to achieve complete remission (CR) by Week 24..

研究的主要终点是无事件生存期（EFS），定义为从随机化开始至治疗失败、缓解后复发或任何原因导致的死亡的时间，以先发生者为准。治疗失败定义为在第24周之前未能达到完全缓解（CR）。

Key secondary endpoints included CR rate, defined as the proportion of participants who achieve a CR; overall survival (OS), defined as the time from date of randomization to the date of death due to any cause; CR and complete remission with partial hematologic recovery (CRh) rate, defined as the proportion of participants who achieve a CR or CRh; and objective response rate (ORR), defined as the rate of CR, CR with incomplete hematologic recovery (CRi) (including CR with incomplete platelet recovery [CRp]), partial remission (PR), and morphologic leukemia-free state (MLFS)..

关键的次要终点包括完全缓解（CR）率，定义为达到CR的参与者比例；总生存期（OS），定义为从随机化日期到因任何原因导致死亡的时间；完全缓解和部分血液学恢复的完全缓解（CRh）率，定义为达到CR或CRh的参与者比例；以及客观缓解率（ORR），定义为CR、不完全血液学恢复的完全缓解（CRi）（包括不完全血小板恢复的完全缓解[CRp]）、部分缓解（PR）和形态学无白血病状态（MLFS）的发生率。