BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)--BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, today announced results from the final analysis of the Phase 3 RATIONALE 305 trial showing tislelizumab plus chemotherapy significantly improved overall survival (OS) in the intent-to-treat (ITT) population as a first-line treatment for patients with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).

巴塞尔，瑞士和北京及剑桥，马萨诸塞州-（商业线）-BeiGene，Ltd。（纳斯达克股票代码：BGNE；HKEX:06160；SSE:688235），一家全球生物技术公司，今天公布的第3阶段THERNATION 305试验的最终分析结果显示，tislelizumab加化疗显着改善了意向治疗（ITT）人群的总生存期（OS），作为晚期胃癌患者的一线治疗或胃食管交界处腺癌（GC/GEJC）。

No new safety signals were identified. Study results will be featured as a late-breaking oral presentation on October 21 at 5:25 p.m. CEST at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract #LBA80)..

没有发现新的安全信号。研究结果将于10月21日下午5:25在欧洲肿瘤内科学会（ESMO）2023年大会（摘要＃LBA80）上作为CEST的最新口头报告。。

“Gastric cancer is a devastating disease that affects millions of people worldwide. Unfortunately, patients with advanced or metastatic conditions have a poor prognosis and urgently need more treatment options in the first-line setting,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene.

“胃癌是一种破坏性疾病，影响全球数百万人。不幸的是，患有晚期或转移性疾病的患者预后不良，迫切需要更多的一线治疗选择，”BeiGene实体瘤首席医疗官Mark Lanasa博士，博士。

“These data show that tislelizumab plus chemotherapy resulted in significant overall survival improvement compared with chemotherapy alone in the intent-to-treat patient group. These results and positive findings build upon the data presented earlier this year in the high PD-L1 expression group and add to the growing body of evidence demonstrating the potential for tislelizumab to help patients with advanced gastric cancer or gastroesophageal junction cancer.”.

“这些数据显示，与意向治疗患者组单独化疗相比，tislelizumab加化疗导致总体生存率显着提高，这些结果和阳性结果基于今年早些时候在高PD-L1表达中提供的数据并增加了越来越多的证据表明tislelizumab有可能帮助患者患有晚期胃癌或胃食管连接癌。”。

In the final analysis of 997 intent-to-treat patients from the Phase 3 RATIONALE 305 trial, tislelizumab plus chemotherapy (oxaliplatin 130 mg/m2 IV Q3W (day 1) and oral capecitabine 1000 mg/m2 twice daily (days 1-14) Q3W (XELOX), or cisplatin 80 mg/m² IV Q3W (day 1) and 5-fluorouracil 800 mg/m2/day IV (days 1-5) Q3W (FP)) showed a median OS of 15.0 months compared with an OS of 12.9 months for chemotherapy alone (HR: 0.80 [95% CI: 0.70, 0.92]; P = 0.0011) in first line advanced GC/GEJC..

在对来自3期RENATION 305试验的997名意向治疗患者的最终分析中，tislelizumab加化疗（奥沙利铂130 mg/m2 IV Q3W（第1天）和口服卡培他滨1000 mg/m2每日两次（第1-14天））Q3W（XELOX），或顺铂80 mg/m²IV Q3W（第1天）和5-氟尿嘧啶800 mg/m2/天IV（第1-5天）Q3W（FP））显示中位OS为15.0个月，而单独化疗的OS为12.9个月HR:0.80[95%CI:0.70,0.92]；P=0.0011）在一线高级GC/GEJC中。。

“The data from the RATIONALE 305 study suggest that tislelizumab plus chemotherapy represents a potential new first-line treatment option for patients with advanced GC/GEJC regardless of PD-L1 expression status,” said Rui-Hua Xu, M.D., Ph.D., Director of the Cancer Control Center of Sun Yat-sen University and principal investigator for the RATIONALE 305 trial.

“来自RESION 305研究的数据表明，无论PD-L1表达状态如何，tislelizumab加化疗对于晚期GC/GEJC患者都是一种潜在的新的一线治疗选择，”中山大学癌症控制中心主任兼RESION 305试验首席研究员徐瑞华博士说。

“Tislelizumab plus chemotherapy provided significant and clinically meaningful overall survival benefit versus chemotherapy in all randomized patients with previously untreated, HER2-negative advanced GC/GEJC.”.

“Tislelizumab加化疗在所有未经治疗的HER2阴性晚期GC/GEJC随机患者中提供了显着且具有临床意义的总体生存获益与化疗相比。”。

In the trial, tislelizumab plus chemotherapy was associated with a higher objective response rate (ORR) (47.3% vs. 40.5%) and median duration of response (mDoR) (8.6 months vs. 7.2 months) compared to placebo plus chemotherapy alone. Median progression-free survival (PFS) for tislelizumab plus chemotherapy was 6.9 months vs.

在该试验中，与单独使用安慰剂加化疗相比，tislelizumab加化疗与更高的客观反应率（ORR）（47.3%对40.5%）和中位反应持续时间（mDoR）（8.6个月对7.2个月）相关。tislelizumab加化疗的中位无进展生存期（PFS）为6.9个月vs。

6.2 months respectively; (HR: 0.78 [95% CI: 0.67, 0.90])..

分别为6.2个月；（HR:0.78[95%CI:0.67,0.90]）。。

About RATIONALE 305 (NCT03777657)

关于理由305（NCT03777657）

RATIONALE 305 is a randomized, double-blind, placebo-controlled, global Phase 3 trial comparing the efficacy and safety of tislelizumab combined with platinum and fluoropyrimidine chemotherapy and placebo combined with platinum and fluoropyrimidine chemotherapy as a first-line treatment for patients with advanced unresectable or metastatic GC/GEJ adenocarcinoma.

理论依据305是一项随机，双盲，安慰剂对照的全球3期临床试验，比较了tislelizumab联合铂和氟嘧啶化疗和安慰剂联合铂和氟嘧啶化疗作为晚期患者一线治疗的疗效和安全性不可切除或转移性GC/GEJ腺癌。

A total of 997 patients from 13 countries and regions across the world were enrolled and randomized 1:1 to receive either tislelizumab or placebo in combination with chemotherapy..

来自世界13个国家和地区的997名患者被纳入并随机1:1接受tislelizumab或安慰剂联合化疗。。

The primary endpoint for the trial is OS, with prespecified hierarchy testing for the PD-L1 high population followed by the ITT population. High PD-L1 expression is defined as PD-L1 score ≥ 5% by VENTANA SP263 assay, assessed by blinded independent central laboratory. OS analysis in the ITT population would be performed only after the OS analysis in the PD-L1 high population was demonstrated to be statistically significant, favoring the tislelizumab and chemotherapy arm.

该试验的主要终点是OS，对PD-L1高人群进行预先指定的等级测试，然后是ITT人群。高PD-L1表达定义为VENTANA SP263测定的PD-L1评分≥5%，由盲法独立中心实验室评估。ITT人群中的OS分析仅在PD-L1高人群中的OS分析被证明具有统计学显着性后才进行，有利于tislelizumab和化疗组。

Secondary endpoints include progression-free survival, overall response rate, duration of response, and safety..

次要终点包括无进展生存期，总有效率，反应持续时间和安全性。。

Interim results were shared in an oral presentation at the 2023 ASCO Gastrointestinal Cancers Symposium. In patients with GC/GEJC with high PD-L1 expression, tislelizumab plus chemotherapy demonstrated statistically significant and clinically meaningful improvement in OS versus placebo plus chemotherapy [median OS: 17.2 vs 12.6 months; HR 0.74 (95% CI 0.59, 0.94); P=0.0056] with a manageable safety profile, and no new safety signals were identifiedi..

在2023年ASCO胃肠癌研讨会的口头报告中分享了中期结果。在具有高PD-L1表达的GC/GEJC患者中，tislelizumab加化疗显示OS与安慰剂加化疗相比具有统计学显着和临床意义的改善[中位OS:17.2对12.6个月；HR 0.74（95%CI 0.59,0.94）；P=0.0056]具有可管理的安全性，并且没有识别出新的安全信号。。

About Tislelizumab

关于Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody, with high affinity and binding specificity against PD-1, specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.ii,iii,iv,v.

Tislelizumab是一种人源化IgG4抗PD-1单克隆抗体，对PD-1具有高亲和力和结合特异性，专门设计用于最大限度地减少与巨噬细胞上Fcγ（Fcγ）受体的结合，有助于帮助人体免疫细胞检测和对抗肿瘤。在临床前研究中，已显示与巨噬细胞上的Fcγ受体结合通过激活抗体依赖性巨噬细胞介导的T效应细胞杀伤来损害PD-1抗体的抗肿瘤活性.ii，iii，iv，v。

The tislelizumab development program encompasses 21 registration-enabling clinical trials in more than 30 countries and regions. To date, BeiGene has announced positive readouts from 10 Phase 3 pivotal studies across multiple tumor types and disease settings, such as NSCLC, small cell lung cancer, gastric cancer, ESCC, hepatocellular cancer, and nasopharyngeal cancer.

tislelizumab开发计划涵盖21个注册，可在30多个国家和地区进行临床试验。迄今为止，BeiGene已宣布来自多种肿瘤类型和疾病环境（如NSCLC，小细胞肺癌，胃癌，ESCC，肝细胞癌和鼻咽癌）的10项3期关键性研究的阳性读数。

More information on the clinical trial program for tislelizumab can be found at: https://www.beigene.com/en-us/science-and-product-portfolio/pipeline..

有关tislelizumab临床试验计划的更多信息，请访问：https://www.beigene.com/en-us/science-and-product-portfolio/pipeline..

Tislelizumab is currently under review by the U.S. Food and Drug Administration (FDA) and received approval by the European Commission for advanced or metastatic ESCC after prior chemotherapy. Additionally, the FDA recently accepted for review a Biologics License Application for tislelizumab as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC.

Tislelizumab目前正在接受美国食品和药物管理局（FDA）的审查，并在之前的化疗后获得欧盟委员会批准用于晚期或转移性ESCC。此外，FDA最近接受审查tislelizumab的生物制剂许可申请，作为不可切除，复发，局部晚期或转移性ESCC患者的一线治疗。

The European Medicines Agency (EMA) is reviewing a marketing authorization application for tislelizumab as a treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy, and in combination with chemotherapy for previously untreated locally advanced or metastatic NSCLC..

欧洲药品管理局（EMA）正在审查tislelizumab的上市许可申请，作为先前化疗后局部晚期或转移性非小细胞肺癌（NSCLC）的治疗，以及与先前未治疗的局部晚期或转移性化疗联合治疗NSCLC。。

Regulatory submissions for tislelizumab are also under review by authorities in Australia, Brazil, China, Korea, Israel, New Zealand, Singapore, Switzerland, and the U.K. Tislelizumab is approved for 11 indications in China and is the leading PD-1 inhibitor in the country.

澳大利亚，巴西，中国，韩国，以色列，新西兰，新加坡，瑞士的当局也正在审查tislelizumab的监管提交，英国的tislelizumab在中国被批准用于11种适应症，是该国领先的PD-1抑制剂。

About BeiGene

关于贝金

BeiGene is a global biotechnology company that is discovering and developing innovative oncology treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations.

BeiGene是一家全球生物技术公司，正在发现和开发创新的肿瘤治疗方法，使全球癌症患者更加负担得起和容易获得。凭借广泛的投资组合，我们正在通过内部能力和合作加快我们各种新型治疗药物的开发。

We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn and X (formerly known as Twitter)..

我们致力于为更多需要它们的患者从根本上改善获得药物的机会。我们日益增长的全球团队拥有超过10000名同事，分布在五大洲，在美国巴塞尔和剑桥设有行政办公室。要了解有关BeiGene的更多信息，请访问www.BeiGene.com并关注LinkedIn和X（以前称为Twitter）。。

Forward-Looking Statements

前瞻性声明

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the potential for tislelizumab to help patients with advanced gastric cancer or gastroesophageal junction cancer; the future development, regulatory filing, approval and commercialization of tislelizumab; and BeiGene’s plans, commitments, aspirations, and goals under the heading “About BeiGene.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing, and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene's reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; and those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent.

本新闻稿包含1995年“私人证券诉讼改革法”和其他联邦证券法含义的前瞻性声明，包括关于tislelizumab帮助晚期胃癌或胃食管连接癌患者的潜力的声明；tislelizumab的未来发展，监管申请，批准和商业化；以及BeiGene在“关于BeiGene”标题下的计划，承诺，愿望和目标。由于各种重要因素，包括BeiGene展示其候选药物的有效性和安全性的能力，实际结果可能与前瞻性声明中指出的结果大不相同；其候选药物的临床结果，可能不支持进一步开发或上市批准；监管机构的行动，可能影响临床试验和上市批准的启动，时间和进展；如果获得批准，BeiGene能够为其上市药物和候选药物取得商业成功；BeiGene获得和维护药品和技术知识产权保护的能力；BeiGene依靠第三方进行药物开发，制造，商业化和其他服务；BeiGene在获得监管部门批准和药品商业化方面的经验有限，并且能够为运营获得额外资金，完成候选药物的开发并实现和保持盈利能力；这些风险在BeiGene最近的10-Q季度报告中的“风险因素”部分以及BeiGene随后的潜在风险，不确定性和其他重要因素的讨论中得到了更充分的讨论。

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