Nivolumab

刚刚，科济生物震撼官宣，其针对Claudin18.2蛋白的自体嵌合抗原受体T细胞疗法候选产品satricabtagene autoleucel（“satri-cel”，CT041）的新药上市申请（NDA）已向中国国家药品监督管理局（NMPA）药品审评中心（CDE）提交，用于治疗Claudin18.2基因阳性的晚期胃/胃食管连接部腺癌（G/GEJA），且该患者至少接受过两线或三线疗法治疗失败。值得一提的是，satri-cel是全球首个也是唯一一个已提交用于治疗实体瘤新药上市申请的嵌合抗原受体T细胞疗法产品。 胃癌在全球范围内是发病率和死亡率均位列第五的癌症，而中国是全球胃癌发病率最高的国家之一。大家谈胃癌“色变”的重要原因是胃癌的难治性，大部分患者在确诊时都为晚期，虽然近两年靶向及免疫治疗取得了重大突破，但无进展生存期也仅为6个月，总生存期在8-14个月左右，胃癌患者迫切需要更好的治疗方案。 值得振奋的是，全球首款 Claudin18.2 CAR-T舒瑞基奥仑赛注射液已被 中国国家药监局药品审评中心（CDE）官网纳入优先审批，并正式提交上市申请，适应症为既往接受过至少二线治疗失败的Claudin18.2（CLDN18.2）表达阳性的晚期胃/食管胃结合部（G/GEJ）腺癌。这意味着，如果一切顺利，舒瑞基奥仑赛注射液（satri-cel）将成为 全球首个上市的实体瘤CAR-T产品 ，造福中国及全球胃癌患者！ 生存期翻倍！全球首个实体瘤 CAR-T 疗法改写晚期胃癌生存记录 舒瑞基奥仑赛注射液 是目前 全球唯一一款在中国和美国获得临床试验许可（IND） 的CLDN18.2 CAR-T细胞治疗，有望成为 全球首创产品 ！ 2025年ASCO盛会上，中国研究人员公布了全球首个针对实体瘤特异性靶点 Claudin18.2 的 CAR-T 细胞疗法--CT041（舒瑞基奥仑赛注射液，Satri-cel ）随机对照试验的卓越数据，并发表于国际重磅期刊《柳叶刀》杂志上，引起巨大轰动！证实了 satri - cel 治疗显著延长了既往接受过治疗的 CLDN18.2 阳性胃癌或胃食管交界处癌患者的无进展生存期，并显著提高了总生存期，且安全性可控，有望改写晚期胃癌生存记录！ 这项在中国24个研究中心开展的开放标签、多中心、随机对照试验 (RCT) 旨在比较 CAR-T疗法Satri-cel 与标准治疗 (SOC) 在 CLDN18.2 阳性、至少两线既往治疗失败的晚期胃食管交界处 (G/GEJC) 患者中的疗效和安全性。 当患者对传统治疗耐药后，往往陷入无药可医的绝境。2022 年 3 月 22 日至 2024 年 7 月 29 日期间，研究团队采用 2:1 随机分组，156 例 CLDN18.2 阳性、至少两线治疗失败的患者被分为 Satri-cel 治疗组（104 例）与标准治疗（TPC）组（52 例）。Satri-cel 组接受 250×10⁶个 细胞输注，最多 3 次；TPC 组则由医生选择阿帕替尼、紫杉醇等常规药物治疗。值得关注的是，TPC 组患者在病情进展或不耐受时，符合条件者可交叉接受 Satri-cel 治疗，这一设计更贴近真实临床场景。 数据截止至 2024 年 10 月 18 日的分析结果堪称震撼！ 生存期显著延长 无进展生存期：9.07 个月VS 3.45 个月。在 ITT 人群中，独立审查委员会评估的 Satri - cel 组中位无进展生存期为 3.25 个月，TPC 组中位无进展生存期为 1.77 个月。疾病进展或死亡风险直降 63% ！ 总生存期：14.42 个月VS 11.33 个月。在 ITT 人群中，satri - cel 组的中位总生存期为 7.92 个月，TPC 组的中位总生存期为 5.49 个月。 更值得一提的是，汇总所有接受 Satri-cel 输注的 108 例患者，mOS 达 9.17 个月，远超 TPC（医生选择的治疗） 组未接受该治疗患者的 3.98 个月，充分证实了 Satri-cel 的卓越疗效。 22%晚期胃癌肿瘤显著缩小 经独立审查委员会评估，satri - cel 组确诊客观缓解率为 22% （104 名患者中 23 名），TPC 组为 4% （52 名患者中 2 名）；satri - cel 组疾病控制率为 63%（104 名患者中 65 名），TPC 组为 25%（52 名患者中 13 名）。 该研究的主要研究者、北京肿瘤医院 沈琳教授 表示：“ CT041-ST-01试验是全球首个CAR-T细胞治疗实体瘤的随机对照临床研究。 对于既往接受过大量治疗、治疗选择极其有限且预后不佳的晚期胃癌/胃食管交界处癌患者，satri-cel展现了突破性的疗效和显著的临床获益，包括显著提高的无进展生存期（PFS）、总生存期（OS）和肿瘤缓解率。这为那些无法通过其他疗法治愈的患者带来了新的希望。我们正在进一步探索satri-cel在辅助治疗和一线序贯治疗中的潜力，旨在更早地干预疾病进程，延长患者生存期，并最终寻求治愈方案。” 这项试验的成功，不仅为晚期 G/GEJC 癌患者点亮了生命之光，更标志着实体瘤细胞治疗时代的真正来临。随着 Satri-cel 加速迈向临床应用，我们有理由期待，未来将有更多癌症患者受益于这一创新疗法，见证生命奇迹的发生！ 晚期胃癌获得完全缓解！中国CAR-T疗法造福全球患者！ 2020年7月，美国FDA正式批准了中国的CAR-T疗法CT041开展临床实验，这项1b 期多中心开放标签研究 ( NCT04404595 )正在美国 6 个地点开展临床试验，众多美国胃癌患者已成功入组。近期，美国两家知名的癌症中心分别报道了两位幸运的患者达到完全缓解和部分缓解，这意味着，中国CAR-T疗法正站在世界舞台绽放璀璨光芒，造福全球患者！ 30岁年轻晚期印戒细胞胃癌患者CAR-T治疗后获得完全缓解！ 2019年12月，不到30 岁的M先生确诊为晚期胃印戒细胞癌，膀胱顶和腹膜壁转移。在接受了4种全身毒性化疗方案以及多次细胞减灭手术联合腹腔热灌注化疗 (HIPEC) 后，病情仍在在不断进展。 2021 年 5 月，M先生参加了CT-041 CAR-T细胞疗法在美国进行的临床试验，第一次CAR-T细胞回输后，他可以吃一些固体食物，并在约 5 个月后首次进行直肠排便。第二次回输后仅4 周，M先生的影像检查结果显示肿瘤靶病灶竟然全部消失，达到了 完全缓解（CR） ，并且脾周结节和胃壁增厚完全消退，更让人无法相信的是，血液层面追踪体内残存细胞的ctDNA 检测结果显示为 阴性 ，这意味着M先生体内已经没有分子残留疾病 （MRD） ！而且第二次回输M先生没有皮疹，他的精力水平显著提高，使他能够独立照顾孩子。在第一次 CT041 输注后 8 个月 ，M先生持续处于完全缓解状态！这也是海外报道的首例Claudin18.2 CAR-T治疗后达到完全缓解的胃癌患者！ 美国MD安德森公布治疗案例 全美癌症专科排名第一的MD安德森癌症中心在癌症免疫治疗学会(SITC)年会上公布了一例振奋人心的案例。 一名57岁男性的晚期胃癌（HER2阴性，PD-L1 CPS 10%）患者，肿瘤已经转移至肝脏，在接受5个周期的FOLFOX+Nivolumab方案和4个周期的FOLFIRI/Ramucirumab方案治疗后病情仍在不断进展。幸运的是，他在全美癌症专科排名第一MD安德森癌症进行了CLDN18.2的检测，显示为阳性，幸运的入组了全新的疗法--中国CAR-T的临床试验。 在预处理化疗后接受了第一次6亿个CT041细胞的治疗，影像显示肿瘤大小分别减小了 19.2%、24.4%和26.9% 。首次回输三个月后，患者接受了第二次6亿个CT041细胞的输注。CT扫描显示，与基线相比，肿瘤持续缩小，分别减小了 34.6% （首次输注后4个月）和 41.0% （首次输注后5个月）。 并且，这款CAR-T的安全性良好，截至目前，患者未报告发生严重不良事件，也未报告发生与胃肠道出血相关的不良事件（AE）。仅报告了短暂的3级或4级血液学毒性事件，其他所有AE均为1级或2级。 关于 Satri-cel Satri-cel 是中国科济生物自主研发的一款针对 Claudin18.2 的自体 CAR-T 细胞候选产品，用于胃癌/胃食管交界处癌 (GC/GEJ) 和胰腺癌 (PC)等 Claudin18.2 阳性实体瘤。正在全球进行多项临床试验： 研究者发起的试验 (CT041-CG4006, NCT03874897)； 针对中国晚期 GC/GEJ 的确认性 II 期临床试验 (CT041-ST-01, NCT04581473)； 针对中国 PC 辅助治疗的 I 期临床试验 (CT041-ST-05, NCT05911217) ； 针对北美晚期胃或胰腺腺癌的 1b/2 期临床试验 (CT041-ST-02, NCT04404595)。 2022 年 1 月，Satri-cel 获得美国 FDA 授予的再生医学先进疗法 (RMAT) 资格，用于治疗 Claudin18.2 阳性晚期 GC/GEJ 癌，并于 2021 年 11 月获得 EMA 授予的 PRIME 资格，用于治疗晚期胃癌。2020 年，Satri-cel 获得美国 FDA 授予的孤儿药资格，用于治疗 GC/GEJ，2021 年获得 EMA 授予的孤儿药资格，用于治疗晚期胃癌。 目前，中国首创 Claudin18.2 CAR-T（Satri-cel）GC/GEJ 关键 II 期临床试验患者入组也已经完成，我们期待这款卓越的疗法能够早日上市，造福更多的患者！ 胃癌患者一定要检测的新兴靶点--Claudin18.2 Claudin 18.2 是一个泛肿瘤的靶点，在多种上皮肿瘤当中都有表达，尤其在胃癌和胰腺癌中存在较高的表达。在胃癌或胃食管结合部癌中，高达60%的患者检测到Claudin 18.2的高度表达，成为近两年最具潜力的热门靶点，已有大量药物取得卓越的临床数据，为胃癌患者带来新曙光！ 2024年6月25日，FDA批准zolbetuximab上市，联合含氟嘧啶和铂类化疗用于一线治疗治疗 CLDN18.2 阳性、不可切除、晚期或复发性胃癌或胃食管交界腺癌患者。这是第一个也是唯一一个靶向治疗患有CLDN18.2 阳性这种毁灭性疾病的新选择！ 除了上面获批的药物，还有更多的新药正在研发中，包括ADC药物、MET抑制剂、PD-1/PD-L1抑制剂等等，大家可以根据当前疾病的发展情况以及分子分型进行选择，也可联系全球肿瘤医生网医学部（400-666-7998）了解详细招募标准，进行入组评估。 M108 试验药组LM302注射液药物介绍CLDN18.2ADCC单克隆抗体适合患者无法手术切除初治胃癌，需要CLDN18.2 表达阳性。HER-2 阴性的胃和胃食管结合部腺。 TQB2103 试验药组TQB2103药物介绍Claudin 18.2ADC适合患者标准治疗后不耐受或进展，需要CLDN18.2 表达检测。HER-2 阴性的胃和胃食管结合部腺癌 相信上面这些在研药物给了晚期胃癌患者新的希望，同时也能看出，随着新型临床研究的推进，对检测提出了更高要求，需要全面了解患者的基因图谱 ，已经做了检测的病友可提交病历至 全球肿瘤医生网医学部 初步评估获得用药方案及临床试验推荐。相信胃癌患者的明天会越来越好。 #方舟基因宝藏计划# “方舟基因宝藏计划“ 由全球肿瘤医生网联合无癌家园、权威基因检测机构、国际药厂、知名肿瘤中心发起的基因“寻宝”行动。本计划旨在深度挖掘每一份基因检测报告提示的生存希望，为肿瘤患者全面解读基因检测报告，并在全球范围内为肿瘤患者匹配适合的上市新药和在研药物临床试验，为患者找到新的生存机遇和上市新药及未上市新药免费治疗的机会！ 想参加的病友可以将基因检测报告，诊断报告电子版或拍照发送至doctor.huang@globecancer.com,邮件中留下联系方式，医学部收到报告分析完毕后一个工作日内电话联系。 本文为全球肿瘤医生网原创，未经授权严禁转载 文献来源：Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician's choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial Qi, Changsong et al. 本文为全球肿瘤医生网原创，未经授权严禁转载

At an Interim Analysis, Bemarituzumab Plus Chemotherapy Significantly Improved Overall Survival in People With FGFR2b Overexpression Compared to Chemotherapy Alone SHANGHAI & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jun. 30, 2025-- Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today announced the Phase 3 FORTITUDE-101 clinical trial evaluating first-line bemarituzumab plus chemotherapy (mFOLFOX6) met its primary endpoint of overall survival (OS) at a pre-specified interim analysis. Bemarituzumab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS as compared to placebo plus chemotherapy in people living with unresectable locally advanced or metastatic gastric or gastroesophageal junction (G/GEJ) cancer with FGFR2b overexpression and who are non-HER2 positive. FGFR2b overexpression was defined as 2+/3+ staining in ≥10% of tumor cells by centrally performed immunohistochemistry (IHC) testing. Gastric cancer is the fifth leading cause of cancer-related death worldwide, with nearly one million new cases and over 650,000 deaths globally each year 1, highlighting a critical unmet medical need. In China, there are over 350,000 new cases each year. The disease is associated with a poor prognosis, particularly in advanced stages where the five-year survival rate is less than 10%. There are currently no approved therapies specifically targeting FGFR2b overexpression in gastric cancer in China. “Bemarituzumab is the first FGFR2b inhibitor to demonstrate a statistically and clinically significant overall survival benefit in a randomized Phase 3 trial for the first-line treatment of FGFR2b-positive gastric cancer,” said Dr. Rafael Amado, M.D., President, Head of Global Research and Development at Zai Lab. “The success of the global Phase 3 FORTITUDE-101 study highlights the potential of bemarituzumab to redefine the standard of care for a patient population that has faced poor outcomes with existing therapies. We are proud to have contributed meaningfully to this pivotal trial, including a substantial number of patients enrolled in China. Based on these results, and the regulatory Breakthrough Designation, we plan to move rapidly toward regulatory submission in China to bring this transformative therapy to patients as quickly as possible.” The most common treatment-emergent adverse events (>25%) in patients treated with bemarituzumab plus chemotherapy were reduced visual acuity, punctate keratitis, anaemia, neutropenia, nausea, corneal epithelium defect and dry eye. While ocular events were consistent with the Phase 2 experience and observed in both arms, they occurred with greater frequency and severity in the Phase 3 bemarituzumab arm. Detailed results from the trial will be shared at a future medical meeting. Zai Lab holds the development and commercialization rights for bemarituzumab for mainland China, Hong Kong, Macau, and Taiwan. Bemarituzumab has been granted Breakthrough Therapy designation by the China Center for Drug Evaluation of the National Medical Products Administration for the treatment of FGFR2b-positive gastric and gastroesophageal junction adenocarcinoma. A Phase 3 study of bemarituzumab plus chemotherapy and nivolumab is also ongoing in patients with first-line gastric cancer, with data readout anticipated in H2 2025. About FGFR2b The FGFR2b protein (also known as fibroblast growth factor receptor 2b) is an emerging biomarker which, when overexpressed, promotes aberrant signaling leading to tumor cell proliferation.2 The FGFR2b protein is overexpressed by G/GEJ tumor cells in approximately 38% of patients with advanced G/GEJ cancer. FGFR2b protein overexpression is defined as 2+/3+ staining intensity on tumor cell membrane, as detected by immunohistochemistry (IHC) testing. In approximately 16% of patients with advanced G/GEJ cancer, FGFR2b protein overexpression is observed on ≥10% of tumor cells by IHC.3 About FORTITUDE-101 FORTITUDE-101 is a randomized, multi-center, double-blind, placebo-controlled Phase 3 study of bemarituzumab plus mFOLFOX6 versus placebo plus mFOLFOX6 as first-line therapy in advanced G/GEJ cancer with FGFR2b overexpression. The FORTITUDE-101 trial spanned 300 sites across 37 countries, with 547 patients enrolled. The primary outcome measure of the trial is overall survival in patients with FGFR2b ≥10% 2+/3+ tumor cell staining. Key secondary outcome measures include progression-free survival and overall response rate. Candidates were excluded from the trial if they were known to be human epidermal growth factor receptor 2 (HER2) positive. FORTITUDE-101 included more comprehensive ocular-related monitoring than previous studies of bemarituzumab. About Gastric Cancer in China Gastric cancer is the fifth most common cancer worldwide, while China bears one of the highest gastric cancer burdens in the world with an estimated 358,700 new cases and 260,400 deaths annually.4 In China, approximately 80% of gastric cancer patients are diagnosed at an advanced or metastatic stage5. For those diagnosed with Stage IV gastric cancer, the overall 5-year survival rate is less than 10%6. Patients with advanced gastric and GEJ cancer that overexpress the FGFR2b protein may be associated with poor prognosis7-10. About Zai Lab Zai Lab is an innovative, research-based, commercial-stage biopharmaceutical company based in China and the United States. We are focused on discovering, developing, and commercializing innovative products that address medical conditions with significant unmet needs in the areas of oncology, immunology, neuroscience, and infectious disease. Our goal is to leverage our competencies and resources to positively impact human health worldwide. For additional information about Zai Lab, please visit www.zailaboratory.com or follow us at www.X.com/ZaiLab_Global, www.twitter.com/ZaiLab_Global. Zai Lab Forward Looking Statements This press release contains forward-looking statements relating to our future expectations, plans, and prospects, including, without limitation, statements regarding the prospects and plans for developing and commercializing bemarituzumab, the potential benefits of bemarituzumab, and the potential treatment of gastric and gastroesophageal junction cancer. All statements, other than statements of historical fact, included in this press release are forward-looking statements, and can be identified by words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would,” and other similar expressions. Such statements constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not statements of historical fact or guarantees or assurances of future performance. Forward-looking statements are based on our expectations and assumptions as of the date of this press release and are subject to inherent uncertainties, risks, and changes in circumstances that may differ materially from those contemplated by the forward-looking statements. We may not actually achieve the plans, carry out the intentions, or meet the expectations or projections disclosed in our forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including but not limited to (1) our ability to successfully commercialize and generate revenue from our approved products, (2) our ability to obtain funding for our operations and business initiatives, (3) the results of our clinical and pre-clinical development of our product candidates, (4) the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approvals of our product candidates, (5) risks related to doing business in China, and (6) other factors identified in our most recent annual and quarterly reports and in other reports we have filed with the U.S. Securities and Exchange Commission (SEC). We anticipate that subsequent events and developments will cause our expectations and assumptions to change, and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Our SEC filings can be found on our website at www.zailaboratory.com and the SEC’s website at www.sec.gov. REFERENCES View source version on businesswire.com: https://www.businesswire.com/news/home/20250630980449/en/ For more information, please contact: Investor Relations: Christine Chiou / Lina Zhang +1 (917) 886-6929 / +86 136 8257 6943 christine.chiou1@zailaboratory.com / lina.zhang@zailaboratory.com Media: Shaun Maccoun / Xiaoyu Chen +1 (857) 270-8854 / +86 185 0015 5011 shaun.maccoun@zailaboratory.com / xiaoyu.chen@zailaboratory.com Source: Zai Lab Limited