A Phase III, Multicentre, Randomised Controlled Study of Sonesitatug Vedotin in Combination With Capecitabine With or Without Rilvegostomig in First-Line Claudin18.2-Positive, HER2-Negative, Advanced/Metastatic Gastric, Gastroesophageal Junction, or Esophageal Adenocarcinoma (CLARITY-Gastric 02)

The purpose of this study is to evaluate the efficacy and safety of sonesitatug vedotin in combination with capecitabine with or without rilvegostomig in first-line (1L) Claudin18.2 (CLDN18.2)-positive, human epidermal growth factor receptor 2 (HER2)-negative, gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.

开始日期2026-02-03

申办/合作机构

AstraZeneca PLC

NCT07143604

/ Active, not recruiting临床2期

A Phase II, Multicentre, Open-label, Single-arm Study of AZD0901 Monotherapy in Second-or Later-Lines Adult Participants With Advanced/Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2

The purpose of this study is to measure the efficacy and safety of AZD0901 monotherapy as 2L+ treatment for participants with advanced or metastatic gastric or GEJ adenocarcinoma expressing CLDN18.2.

开始日期2025-08-29

申办/合作机构

AstraZeneca PLC

NCT07069712

/ Recruiting临床2期

A Master Protocol of an Open-Label, Multi-Drug, Multi-Center, Phase II Platform Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of Novel Agents or Combinations as Perioperative Treatment in Participants With Locally Advanced Resectable Gastroesophageal Adenocarcinoma (GEMINI-PeriOp GC)

GEMINI-PeriOp GC study will assess the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of novel agents or novel combinations as perioperative treatment in participants with locally advanced resectable gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma who have not received previous treatment for the disease.

开始日期2025-07-17

申办/合作机构

AstraZeneca PLC

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100 项与 Sonesitatug vedotin 相关的专利（医药）

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项与 Sonesitatug vedotin 相关的文献（医药）

2026-12-31·mAbs

Antibodies to watch in 2026

Review

作者: Pinto, Kieran ; Kapoor, Vaishali ; Kaplon, Hélène ; Crescioli, Silvia ; Reichert, Janice M. ; Chenoweth, Alicia ; Hsu, Yu-Shin

The Antibodies to Watch article series provides annual updates on commercial late-stage clinical development, regulatory review, and marketing approvals of antibody therapeutics. Since the first article was published in 2010, the late-stage pipeline has grown from 26 antibody therapeutics to over 200, while during the same time numerous molecules in late-stage studies either transitioned to regulatory review and were approved or were terminated. In this installment of the series, we recap first marketing approvals granted to 19 antibody therapeutics in 2025, discuss 26 molecules currently in regulatory review, including the bispecific antibody-drug conjugate izalontamab brengitecan, and predict which molecules of the 209 currently in the commercial late-stage pipeline might transition to regulatory review by the end of 2026. Most antibody therapeutics in the latter category are for non-cancer indications (16/21, 76%) and have a conventional format (13/21, 62%), but the category also includes numerous antibody-oligo or -drug conjugates, such as delpacibart etedesiran, delpacibart zotadirsen, zeleciment rostudirsen, sonesitatug vedotin, trastuzumab pamirtecan, and ifinatamab deruxtecan, as well as the bispecific petosemtamab. As antibody therapeutics development is a global enterprise, we also discuss trends in annual first approvals granted to antibody therapeutics in any country since 2010, stratified by the antibody's country of origin, documenting the notable increases in the total number of first approvals and those approved first in China. Finally, to benchmark the time typically required for clinical development and regulatory review, we calculated this period for recently approved antibody therapeutic products stratified by their therapeutic area, mechanism of action, format, and country of origin. Our data show that the development and approval period were typically ~6 years, but on average this period was shorter for China-originated products.

2025-02-01·LANCET ONCOLOGY

Claudin 18.2-targeting antibody–drug conjugate CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer (KYM901): a multicentre, open-label, single-arm, phase 1 trial

Article

作者: Wang, Zhen-Ning ; Shi, Xi ; Yang, Jian-Wei ; Luo, Su-Xia ; Liu, Fu-Rong ; Chen, Zhen-Dong ; Wu, Xiao-Jie ; Zhuang, Zhi-Xiang ; Ruan, Dan-Yun ; Chen, Bo ; Liang, Xiao-Hua ; Xu, Rui-Hua ; Liu, Fu-Nan ; Kumar, Rakesh ; Wei, Xiao-Li ; Zheng, Yu-Long ; Liu, Wei ; Zhang, Yan-Qiao ; Wang, Jun-Ye ; Zhang, Dong-Sheng ; Liu, Jian ; Wang, Yong-Sheng

BACKGROUND:

CMG901 is a novel first-in-class antibody-drug conjugate with a humanised anticlaudin 18.2 antibody linked to microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the antitumour activity and safety of CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer and other solid tumours.

METHODS:

KYM901 is a multicentre, open-label, single-arm, phase 1 trial consisting of dose-escalation and dose-expansion stages. Patients with advanced solid tumours, including gastric or gastro-oesophageal junction and pancreatic cancers, were recruited from 31 hospital sites in China. Eligible patients were aged 18 years or older, were refractory to standard therapy or had no available standard-of-care regimen, and had an Eastern Cooperative Oncology Group performance status score of 0-1, a life expectancy of at least 3 months, and at least one measurable lesion. Patients received intravenous CMG901 every 3 weeks (0·3-3·4 mg/kg in dose escalation and 2·2-3·0 mg/kg in dose expansion) until disease progression, unacceptable toxic effects, initiation of new antitumour therapy, study withdrawal, or death. Primary endpoints were adverse events and dose-limiting toxic effects in the dose-escalation phase, and objective response rate and recommended phase 2 dose in the dose-expansion phase. Confirmed objective response was defined as a partial or complete response that was verified by follow-up imaging at least 4 weeks after the initial assessment. Safety was assessed in all patients who received at least one dose of CMG901 with at least one post-dose safety evaluation. Antitumour activity was assessed in all patients who received at least one dose of CMG901 (full analysis set) and in all CMG901-treated patients with at least one post-dose imaging evaluation and no major protocol deviations (efficacy analysis set). Dose-expansion data for patients with pancreatic cancer will be published separately. Due to small sample sizes, results in patients with other solid tumours (n=2) are not planned for publication. This ongoing trial is registered with ClinicalTrials.gov, NCT04805307.

FINDINGS:

Between Dec 24, 2020, and Feb 23, 2023, 27 patients were enrolled in the dose-escalation phase (median age 57·0 years [IQR 48·0-63·0]; 14 [52%] male, 13 [48%] female) and 107 patients with gastric or gastro-oesophageal junction cancer in the dose-expansion phase (median age 56·0 years [44·0-64·0]; 57 [53%] male, 50 [47%] female). As of Feb 24, 2024, one dose-limiting toxic effect (grade 3 pancreatitis) occurred at 2·2 mg/kg, and the maximum tolerated dose was not reached in the dose-escalation phase. All 27 patients reported at least one treatment-emergent adverse event, most frequently vomiting (19 [70%]), decreased appetite (16 [59%]), proteinuria (16 [59%]), and anaemia (15 [56%]), and five (19%) had drug-related grade 3 or worse treatment-emergent adverse events. In 107 patients, grade 3 or worse treatment-emergent adverse events occurred in 73 (68%) patients and serious adverse events occurred in 54 (50%) patients in dose expansion. The most common grade 3-4 adverse events were neutrophil count decreased (22 [21%]), anaemia (15 [14%]), and vomiting (11 [10%]). One treatment-related death was reported. At median follow-up of 9·0 months (IQR 4·4-12·9), among 113 patients with gastric or gastro-oesophageal junction cancer in the 2·2-3·0 mg/kg cohort full analysis set across both the dose-escalation and dose-expansion phases, the confirmed objective response rate was 28% (95% CI 20-38; 32 of 113 patients). In the 109 patients included in the efficacy analysis set, the confirmed objective response rate was 29% (95% CI 21-39; 32 of 109 patients). Based on overall safety, activity, and pharmacokinetics of CMG901, 2·2 mg/kg was the proposed recommended phase 2 dose.

INTERPRETATION:

CMG901 showed a manageable safety profile and had promising antitumour activity in patients with advanced gastric or gastro-oesophageal junction cancer.

FUNDING:

KYM Biosciences.

2024-09-01·Cell Reports Medicine

CMG901, a Claudin18.2-specific antibody-drug conjugate, for the treatment of solid tumors

Article

作者: Chen, Bo ; Wang, Ying ; Zhang, Libo ; Liu, Wei ; Xu, Ruihua ; He, Yanyun ; Song, Qin ; Wei, Xiaoli ; Li, Zhiyao ; Liu, Furong ; Xu, Gang ; Wang, Changyu

Claudin18.2 has been recently recognized as a potential therapeutic target for gastric/gastroesophageal junction or pancreatic cancer. Here, we develop a Claudin18.2-directed antibody-drug conjugate (ADC), CMG901, with a potent microtubule-targeting agent MMAE (monomethyl auristatin E) and evaluate its preclinical profiles. In vitro studies show that CMG901 binds specifically to Claudin18.2 on the cell surface and kills tumor cells through direct cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and bystander killing activity. In vivo pharmacological studies show significant antitumor activity in patient-derived xenograft (PDX) models. Toxicity studies show that the major adverse effects related to CMG901 are reversible hematopoietic changes attributed to MMAE. The highest non-severely toxic dose (HNSTD) is 6 mg/kg in cynomolgus monkeys and 10 mg/kg in rats once every 3 weeks. CMG901's favorable preclinical profile supports its entry into the human clinical study. CMG901 is currently under phase 3 investigation in patients with advanced gastric/gastroesophageal junction adenocarcinoma expressing Claudin18.2 (NCT06346392).

1,310

项与 Sonesitatug vedotin 相关的新闻（医药）

2026-10-07

·搜狐新闻

乐普生物（02157.HK）10月7日收盘跌2.49%

证券之星消息，截至2026年10月7日收盘，乐普生物(02157.HK)报收于3.92港元，下跌2.49%，成交量68.9万股，成交额267.6万港元。资金流向数据方面，10月7日乐普生物无主力资金净流入，无超大单资金净流入，无大单资金净流入，中单资金净流入35.99万港元，小单资金净流入29.37万港元。乐普生物科技股份有限公司是一家主要从事医药产品销售及新药研发的公司。该公司聚焦于肿瘤治疗领域，尤其是靶向治疗及免疫治疗。该公司致力于通过抗体药物偶联物（ADC）技术开发平台开发创新型ADC。该公司的临床阶段候选药物涵盖靶向疗法药物和一种免疫治疗药物，具体包括MRG003、MRG002、CMG901、MRG004A、CG0070、MRG006A、MRG007、CTM012等。以上内容为证券之星据公开信息整理，仅供参考不构成投资建议。返回搜狐，查看更多

抗体药物偶联物免疫疗法

2026-10-07

·Biotech前瞻

胃癌治疗的五个新变化：从围术期免疫到精准序贯，从新靶点到腹膜转移

Biotech前瞻｜胃癌治疗进展深度编译胃癌治疗的新消息，已经很难用一款药、一个靶点概括。在可切除胃癌中，免疫治疗提前进入术前、术后，开始拿出长期生存证据；在HER2阳性晚期胃食管腺癌中，双表位抗体联合免疫和化疗，将中位总生存期推至26.4个月；在HER2阴性人群中，双靶点免疫药物与CLDN18.2治疗持续扩展；对于难治的腹膜转移，改变紫杉醇的给药路径，也带来了新的Ⅲ期生存获益。这些进展发生在不同阶段，不能把生存数字放在一起排名。但它们共同提出了一个更实际的问题：面对越来越多的方案，怎样为患者安排从手术前到疾病进展后的治疗？王峰、徐瑞华等团队发表于《CA：临床医师癌症杂志》的综述，连同近期《柳叶刀》《新英格兰医学杂志》《临床肿瘤学杂志》和《JAMA Oncology》的研究，提供了观察这场变化的完整视角。[1–8] Biotech前瞻关注的，既有新方案带来的生存改善，也有其中决定临床应用的细节：研究选了谁、与什么方案比较、毒性是否增加，以及后线还有多少空间。01 围术期免疫进入生存验证阶段，术后减少化疗成为新的研究方向局部进展期胃癌即使完成根治性手术，仍然可能复发。围术期治疗，即手术前后进行全身治疗，旨在控制原发病灶和潜在的微小转移。其价值最终要体现在降低复发风险、延长生存，而不仅是提高切除标本中的肿瘤消退比例。 MATTERHORN的最终总生存分析，让围术期免疫的证据进一步完整。[1] 这项全球Ⅲ期研究随机纳入948例可切除胃癌或胃食管结合部腺癌患者，在FLOT基础上加入度伐利尤单抗或安慰剂。FLOT包含氟尿嘧啶、亚叶酸、奥沙利铂和多西他赛，是含三种细胞毒药物的方案。此前，研究已经证实无事件生存（EFS）改善，HR为0.71；首次主要报告中，病理完全缓解（pCR，即切除的原发灶及淋巴结中未见存活肿瘤）的比例为19.2%与7.2%。此次最终分析进一步显示，总生存（OS）HR为0.78，95%置信区间为0.63—0.96，P＝0.021，达到此次分析预设的显著性标准。两组中位OS均未达到；3年OS率为69%与62%，绝对相差约7个百分点。HR 0.78反映的是死亡风险的相对差异，不能解读为生存时间增加22%。图1｜MATTERHORN最终OS分析，截取原文Figure 2A。绿色为度伐利尤单抗＋FLOT，蓝色为安慰剂＋FLOT。两组中位OS均未达到，3年OS率约为69%与62%。来源：Janjigian等，Lancet，2026。[1] 研究未按PD-L1表达限制入组，总体结果支持这一策略。但低表达亚组的样本和事件数有限，亚组方向相近不等于每类患者都已经独立证实同等获益。MATTERHORN也没有中国患者入组，其FLOT方案在中国实践中的可实施性，需要结合手术质量、体能与营养状态判断。 ASTRUM-006进一步探索：能否把强化治疗放在术前，术后免去化疗？[2] 该研究随机纳入588例PD-L1综合阳性评分（CPS）≥5的可切除胃癌或胃食管结合部腺癌患者，实际入组患者均来自中国。试验组术前接受3个周期斯鲁利单抗联合SOX，SOX由替吉奥和奥沙利铂组成；术后接受最多17个周期斯鲁利单抗单药。对照组术前接受SOX，术后再接受5个周期SOX。在CPS≥10人群，EFS HR为0.65；在全部随机人群，即CPS≥5人群，EFS HR为0.73。全人群pCR率约为22%与6%。术后辅助阶段≥3级治疗相关不良事件约为16%与34%。图2｜ASTRUM-006研究者评估的EFS，截取原文Figure 2A、2B及对应风险人数。左图为CPS≥10，右图为全部随机人群CPS≥5；红色为斯鲁利单抗策略，蓝色为对照。来源：Shen等，Lancet，2026。[2] 胃切除后，进食减少、体重下降及营养恢复困难会影响后续治疗。这个策略因此有现实价值：在经过标志物筛选的患者中，减少术后化疗暴露，同时维持疾病控制。但研究验证的是整套治疗策略，尚不能单独证明术后免疫优于术后化疗，也没有验证根据pCR结果临时决定停化疗。总生存尚未成熟，生活质量优势也不能仅凭不良事件减少就认定已经得到证实。表1｜两项围术期Ⅲ期研究，回答的是不同问题比较项目 MATTERHORN ASTRUM-006 随机人数及筛选 948例；未按PD-L1限制入组 588例；CPS≥5 术前方案度伐利尤单抗＋FLOT 斯鲁利单抗＋SOX，3周期术后方案度伐利尤单抗＋FLOT，再继续免疫单药斯鲁利单抗单药，最多17周期对照围术期FLOT及安慰剂术前3周期、术后5周期SOX EFS HR 0.71 CPS≥5：HR 0.73；CPS≥10：HR 0.65 pCR 首次主要报告：19.2% vs 7.2% 全人群约22% vs 6% OS 最终分析HR 0.78，显著改善尚未成熟主要价值证实围术期免疫的总生存获益支持筛选人群中的术后免化疗策略为什么KEYNOTE-585未获得同样成功，而这两项研究阳性？化疗骨架、标志物筛选、入组疾病构成和统计设计都可能参与其中。奥沙利铂诱导免疫原性细胞死亡，为免疫联合提供了机制依据，但目前不能仅凭跨研究差异，将成败归因于奥沙利铂优于顺铂。[3,8] 《柳叶刀》的配套评论还提醒：术前、术后和延长免疫各自贡献了多少，现有研究无法独立拆分。达到pCR与更好的后续结局相关，也不等于已经证明可以减少治疗或免除手术。[3] 对研发企业而言，下一步需要研究的不只是增加一款药，还包括怎样提高全程治疗完成率，以及哪些患者可以安全地减少治疗。02 HER2双抗强化一线，后线选择需要重新确认靶点 HER2，即人表皮生长因子受体2，是胃癌较早实现精准治疗的靶点。曲妥珠单抗联合化疗建立了治疗基础，KEYNOTE-811随后支持在适合的PD-L1阳性患者中加入帕博利珠单抗。 HERIZON-GEA-01的26.4个月，让HER2治疗继续改善的空间变得具体。[4] 研究共随机纳入914例HER2阳性晚期胃食管腺癌患者，包括胃、胃食管结合部和食管腺癌，比较zanidatamab联合化疗、zanidatamab联合替雷利珠单抗及化疗，与曲妥珠单抗联合化疗。 Zanidatamab是结合HER2两个不同表位的双特异性抗体，两端识别的都是HER2。其结合胞外结构域Ⅱ和Ⅳ，能够交联相邻受体，促进聚集、内化与降解，并通过抗体及补体介导的效应增强杀伤。这些是机制基础，临床优势仍要看随机研究。含zanidatamab的两个方案，中位无进展生存期（PFS）均为12.4个月，对照为8.1个月；相应HR为0.63和0.65。在此次分析中，加入替雷利珠单抗的方案证实OS改善，中位OS为26.4个月与19.2个月，HR为0.72，P＝0.004。未加入替雷利珠单抗的方案中位OS为24.4个月，P＝0.06，尚未达到显著性。图3｜HERIZON-GEA-01原文Figure 2的两组OS比较。上图：zanidatamab＋替雷利珠单抗＋化疗；下图：zanidatamab＋化疗；两者均对照曲妥珠单抗＋化疗。上图证实OS优势，下图本次分析未显著。来源：Shitara等，NEJM，2026。[4] 还需看清对照组：它没有加入PD-1抑制剂。因此，26.4个月不能用来直接宣布优于帕博利珠单抗、曲妥珠单抗和化疗的组合。两项研究的患者和后续治疗不同，中位OS也不能作头对头比较。更深的缓解同时伴随治疗负担。Zanidatamab联合免疫、化疗组≥3级不良事件为83.3%，对照为74.5%；≥3级腹泻为24.8%与12.9%。胃癌患者常伴营养问题，持续腹泻可能影响体能和用药，因此需要与疗效一起评价。一线之后，治疗前的HER2报告也可能失效。[5] Ooki等人的综述指出，不同研究中，曲妥珠单抗治疗后HER2阳性丢失约为30%—70%。这一范围来自不同队列，不能当作所有患者的固定概率。在DESTINY-Gastric04筛选阶段接受中央检测的833例患者中，约32%已丢失HER2阳性。胃癌存在空间和时间异质性。一线治疗可能减少HER2高表达细胞，其他克隆随后扩增；受体下调和内化也可能参与其中。进展时的肿瘤，因而未必适合继续采用初诊时的靶向策略。图4｜HER2动态变化的机制示意，截取原综述Figure 2。图中展示受体内化、降解及不同克隆比例变化，并讨论HER2再表达的可能；底部曲线是概念模型，并非患者实测数据。来源：Ooki等，ESMO Gastrointestinal Oncology，2026。[5] 这与德曲妥珠单抗（T-DXd）的二线证据密切相关。T-DXd属于抗体偶联药物（ADC），将HER2抗体与拓扑异构酶Ⅰ抑制剂载荷连接。DESTINY-Gastric04要求曲妥珠单抗进展后重新活检确认HER2阳性。在该人群中，T-DXd对比紫杉醇联合雷莫西尤单抗，将中位OS从11.4个月提高至14.7个月，HR为0.70。[5] 表2｜HER2治疗从初诊筛选走向进展后再评估研究治疗阶段及比较中位OS，试验组 vs 对照组解读重点 ToGA，Ⅲ期一线；曲妥珠单抗＋化疗 vs 化疗 13.8 vs 11.1个月建立HER2靶向治疗基础 KEYNOTE-811，Ⅲ期一线；帕博利珠单抗加入曲妥珠单抗＋化疗 CPS≥1：20.1 vs 15.7个月此处列CPS≥1亚组，勿与全人群混用 HERIZON-GEA-01，Ⅲ期一线；zanidatamab＋替雷利珠单抗＋化疗 vs 曲妥珠单抗＋化疗 26.4 vs 19.2个月对照未包含PD-1抑制剂 T-ACT，随机Ⅱ期二线；继续曲妥珠单抗＋紫杉醇 vs 紫杉醇约10 vs 10个月未支持常规跨线继续曲妥珠单抗 DESTINY-Gastric04，Ⅲ期二线；T-DXd vs 紫杉醇＋雷莫西尤单抗 14.7 vs 11.4个月入组要求进展后活检仍为HER2阳性表2用于呈现证据演进，不能据此跨研究排列药物优劣。KEYNOTE-811的CPS≥1数据依据对应分析及产品资料，其余主要依据所附研究与综述。[4,5,8,9] 若进展后确认HER2丢失，非HER2靶向方案及临床研究需要重新进入讨论。HER2再表达具有生物学可能，但尚不能据此普遍规定三线前重复活检，更不能保证后续重新靶向有效。循环肿瘤DNA（ctDNA）可辅助观察ERBB2扩增和其他耐药变化，尤其在重新取样困难时。但血液阴性不能排除组织阳性，现有关键二线证据也不支持将ctDNA完全替代组织确认。[5] 对企业而言，一线强化之后的后线布局会越来越重要。Zanidatamab之后是否保持同样的HER2表达和ADC敏感性，需要专门验证，不能直接套用曲妥珠单抗之后的序贯证据。03 HER2阴性免疫治疗继续升级，双靶点仍然需要选择患者对多数HER2阴性晚期患者，免疫联合化疗已形成重要治疗基础。新型免疫药物进一步尝试干预肿瘤微环境，但增加一个作用通路，是否能够扩大获益人群，需要分别验证。 RELIGHT评估的是瑞拉芙普α（retlirafusp alfa，原代号SHR-1701）联合CAPOX，即卡培他滨与奥沙利铂。[6] 它由抗PD-L1抗体与TGF-β受体Ⅱ胞外结构域融合而成，既阻断PD-L1介导的免疫抑制，也捕获转化生长因子β（TGF-β）。TGF-β参与免疫细胞功能抑制及肿瘤微环境变化，双通路干预具有机制依据。研究随机纳入731例HER2阴性晚期胃癌或胃食管结合部腺癌患者。CPS≥5人群中，中位OS为16.8个月与10.4个月，HR为0.53；全部随机人群中为15.8个月与11.2个月，HR为0.66。对照是安慰剂联合CAPOX。图5｜RELIGHT原文Figure 2曲线部分。左列为OS，右列为PFS；上排为CPS≥5，下排为全部随机人群。粉色为瑞拉芙普α＋CAPOX，绿色为对照。全人群阳性结果不能用于概括CPS＜1亚组。来源：Peng等，JCO，2026。[6] 最需要保留的细节，是CPS＜1人群出现了不利生存信号。主要报告中，该亚组中位OS为8.1个月与12.8个月，HR为2.22；后续更新分析的HR仍为1.757，95%置信区间为1.022—3.006。亚组结果需结合样本量与统计性质解释，但不能被全人群阳性结论掩盖。[6] 瑞拉芙普α已在中国获批用于相关胃癌一线治疗，批准人群限定PD-L1 CPS≥1，不能写成适用于所有HER2阴性患者。[10] 安全性方面，试验组≥3级治疗相关不良事件为62.6%，对照为59.0%；部分血液学毒性反而较低，例如血小板计数降低为19.0%与28.1%。论文提出，TGF-β阻断可能影响造血恢复，但这仍是需要验证的解释，不能写成已证实的骨髓保护机制。卡度尼利单抗走的是另一条路径，通过PD-1与CTLA-4双检查点干预增强免疫。COMPASSION-15显示，联合化疗的中位OS为15.0个月与10.8个月，HR为0.62，并在不同PD-L1表达层级观察到获益信号。[8] 不同双靶点方案对低表达患者的结果并不一致，不能用双抗这个类别直接推断人群覆盖能力。表3｜HER2阴性一线研究中的生存数字，需要连同分析人群一起看研究及机制表中对应人群中位OS，试验组 vs 对照组 OS HR CheckMate 649，PD-1 CPS≥5 14.4 vs 11.1个月 0.71 RATIONALE-305，PD-1 全部随机人群 15.0 vs 12.9个月 0.80 RELIGHT，PD-L1/TGF-β CPS≥5 16.8 vs 10.4个月 0.53 RELIGHT，PD-L1/TGF-β 全部随机人群 15.8 vs 11.2个月 0.66 COMPASSION-15，PD-1/CTLA-4 全部随机人群 15.0 vs 10.8个月 0.62 以上均对照各研究中的化疗方案，患者构成与分析时点不同。RATIONALE-305的PD-L1评价采用TAP，不能将其主要筛选标准误写为CPS。表中数据主要依据CA综述及RELIGHT论文所列分析。[6,8] 双靶点的临床价值已经获得一些验证，但如果对照仍是化疗，就还不能分离第二条通路的额外贡献，也不能宣布优于现有PD-1联合化疗。下一步研究需要更贴近当代治疗标准，并解释新方案在哪些人群中值得增加用药成本和管理负担。04 CLDN18.2形成多种治疗方式，序贯价值需要逐步验证 Claudin 18.2（CLDN18.2）是紧密连接蛋白的一种亚型，也是胃癌近年来重要的新靶点。其治疗开发已经覆盖单抗、ADC和嵌合抗原受体T细胞（CAR-T）。[8] 但同一个靶点，并不意味着相同的用药条件。佐妥昔单抗主要通过免疫介导的杀伤发挥作用。SPOTLIGHT与GLOW分别联合mFOLFOX6和CAPOX，在HER2阴性、至少75%肿瘤细胞呈中至强CLDN18.2膜染色的患者中，证实PFS与OS改善。两项研究中位OS分别为18.23个月与15.54个月、14.39个月与12.16个月。[8] 胃黏膜相关的恶心、呕吐等需要主动管理。单抗的应用因此既依赖检测，也依赖输注及支持治疗能力。ILUSTRO中联合化疗和PD-1抑制剂的早期结果，进一步探索了标志物重叠人群的联合治疗，但不能用单臂结果直接宣告优于现有方案。 ADC通过抗体递送细胞毒载荷。Sonesitatug vedotin（CMG901/AZD0901）采用MMAE载荷；SHR-A1904采用拓扑异构酶Ⅰ抑制剂载荷。不同载荷意味着不同的杀伤方式、毒性与耐药问题，靶点相同不代表产品可以互换。 CLARITY-Gastric01已公布三线及以后OS主要终点，以及二线及以后全人群OS关键次要终点阳性。不过，同一公告中，全人群PFS另一主要终点未达到统计学显著，不能写成双主要终点均成功。研究采用至少25%肿瘤细胞表达、任意染色强度的门槛，与佐妥昔单抗的高表达定义不同。[11] CAR-T则将患者T细胞改造后回输，用细胞识别和杀伤CLDN18.2阳性肿瘤。随机Ⅱ期CT041-ST-01中，satri-cel对比医师选择治疗，中位PFS为3.25个月与1.77个月，HR为0.37；ORR为22%与4%。中位OS为7.92个月与5.49个月，HR为0.69，95%置信区间为0.46—1.05，尚不能写成显著OS改善。[8] Satri-cel已于2026年6月在中国获批，用于至少两线治疗失败的CLDN18.2阳性、HER2阴性晚期胃癌或胃食管结合部腺癌。[12] 进入实际应用后，细胞采集、制备等待、清淋治疗及输注后管理，都影响患者能否完成治疗。表4｜同样靶向CLDN18.2，三类治疗的定位并不相同治疗方式代表产品与研究人群或检测门槛核心证据与待解问题单抗佐妥昔单抗；SPOTLIGHT/GLOW 一线；HER2阴性，≥75%细胞中至强膜染色两项Ⅲ期PFS/OS阳性；需做好恶心呕吐及输注管理 ADC，MMAE载荷 Sonesitatug vedotin；CLARITY-Gastric01 二线及以后；≥25%细胞表达，任意强度 OS终点阳性；全人群PFS主要终点未显著 ADC，拓扑异构酶Ⅰ载荷 SHR-A1904；早期研究经治患者；按相应研究检测标准 ORR约24%—25%；后续需随机证据 CAR-T Satri-cel；CT041-ST-01 至少两线治疗后；研究阈值≥40%细胞中至强染色随机Ⅱ期PFS改善并在中国获批；制备及治疗条件影响可及性研究筛选阈值不能代替具体产品说明书，也不能在不同检测平台之间直接换算。[8,11,12] CLDN18.2与HER2可以共同表达，CLDN18.2也可能与PD-L1重叠，不应把它们画成互斥的患者分类。临床需要看实际检测组合，研发则需要回答先用哪类药、进展后靶点是否保留，以及换载荷或换成药形式是否仍有效。 Biotech前瞻认为，CLDN18.2后续竞争的重点会逐渐转向这些具体问题。更低表达门槛扩大了研究覆盖的人群，但只有在对应患者中证实净获益，才能转化为可持续的临床应用。05 腹膜转移出现Ⅲ期新证据，给药路径与系统治疗需要共同考虑腹膜转移是胃癌的难治场景。病灶可伴纤维化、腹水及复杂的局部微环境，全身给药对腹膜病灶的暴露可能不足。这使局部给药具有药理学依据，但生存价值必须通过随机研究验证。 DRAGON-01研究让这一问题有了新的答案。[7] 这项中国多中心、开放标签Ⅲ期研究随机纳入238例患者，主要分析包括222例接受治疗者。入组要求腹腔镜确认腹膜转移，且无腹膜外转移，既往未接受系统治疗。试验组每21天一个周期，在第1、8天静脉给予紫杉醇50 mg/m²，加腹腔紫杉醇20 mg/m²，联合口服替吉奥；对照组静脉紫杉醇70 mg/m²联合替吉奥。每次紫杉醇计划总剂量相同，主要差别是部分剂量直接进入腹腔。中位OS为19.4个月与13.9个月，HR为0.67，P＝0.01；中位PFS为11.2个月与7.2个月。3年OS率为25.0%与12.2%。图6｜DRAGON-01原文Figure 2。上图为OS，下图为PFS；蓝色为腹腔＋静脉紫杉醇联合替吉奥，橙色为静脉紫杉醇联合替吉奥。来源：Yan等，JAMA Oncology，2026。[7] 紫杉醇腹腔清除较慢、局部停留较长，有助于提高腹膜暴露。基线腹膜细胞学阳性患者的转阴率为83.6%与52.6%；转化手术率为50.7%与35.1%。这两个探索性指标提示局部控制改善，但不能把50.7%写成全部获得R0切除。[7] 表5｜腹膜转移的生存获益之外，还要看手术与置管负担指标腹腔＋静脉组静脉组中位OS 19.4个月 13.9个月中位PFS 11.2个月 7.2个月转化手术率 50.7%（75/148） 35.1%（26/74）手术者中的R0切除率 84.0%（63/75） 84.6%（22/26） 3—4级不良事件 38.5% 41.9% 腹腔输注港相关并发症 27.0%；10.8%需外科干预不适用 R0指切缘无肿瘤残留，表中分母为接受转化手术者。转化手术等探索性结果存在选择偏倚，不宜据此断言手术带来全部生存改善。[7] 接受转化手术的腹腔组患者中位OS为33.1个月，但这类患者已经经过治疗反应和手术条件的筛选。相关比较还存在时间相关偏倚，不能用来证明所有腹膜转移患者都应争取手术。同样，重度全身不良事件未增加，也不等于没有额外负担。输注港维护、并发症处理和多次腹腔评估，需要经验丰富的团队。研究未收集患者报告结局，患者日常生活负担尚未得到充分衡量。对照方案也未包含当代常用的免疫或靶向药物。下一步更重要的是确定腹腔给药如何与现代系统治疗结合，并找到能稳定获益、可以持续接受治疗的人群。胃癌下一阶段的竞争，需要把全程治疗衔接起来这批文献的共同启示，是胃癌治疗正在变得更细。可切除患者需要考虑怎样降低复发风险，以及是否有机会减少术后治疗。晚期患者的HER2、PD-L1、错配修复功能或微卫星不稳定状态（MMR/MSI）、CLDN18.2，应尽早进入治疗规划；一旦进展，某些靶点还需要再次评估。腹膜转移等特殊场景，则需要额外考虑药物分布和局部治疗条件。对于错配修复缺陷或高度微卫星不稳定（dMMR/MSI-H）患者，免疫单药或免化疗策略具有研究基础，但不应将探索性结果普遍写成免除手术或按病理缓解自由调整术后方案的标准。多组学分型、ctDNA和人工智能可以帮助提出更细的分层，真正改变用药还需要前瞻性验证。从行业角度看，单抗、双抗、ADC和CAR-T已经让胃癌产品布局更丰富。后续差异化会更多体现在具体使用条件：能否对照现有标准取得额外生存获益，能否扩大有证据支持的治疗人群，是否更容易完成疗程，以及能否保留有效的后线选择。这也要求研发更早考虑临床衔接。检测门槛改变，需要病理标准配合；围术期药物前移，需要证明长期价值；细胞治疗进入医院，需要制备与患者管理能力；腹腔治疗产生生存获益，也需要降低置管和维护负担。 Biotech前瞻既关注疗效明显进步的产品，也关注失利研究、阴性亚组和延长随访后减弱的获益。它们帮助我们判断哪些机制值得继续开发，哪些方案需要重新选择患者。 26.4个月的中位OS、术后免化疗的探索，以及腹膜转移Ⅲ期阳性，都值得期待。接下来要做的是将这些成果放回各自适用的患者和治疗阶段，并验证如何前后衔接。患者获得更多选择之后，也需要有证据支持的治疗顺序，以及能够真正完成的治疗安排。参考文献与核验来源 1. Janjigian YY, et al. MATTERHORN final OS analysis. Lancet. 2026;408:1114–1128. DOI: 10.1016/S0140-6736(26)01254-7 . 2. Shen L, et al. ASTRUM-006. Lancet. 2026;407:2542–2553. DOI: 10.1016/S0140-6736(26)00974-8 . 3. Perioperative immunotherapy goes global in gastro-oesophageal cancer. Lancet. 2026. DOI: 10.1016/S0140-6736(26)01425-X . 4. Shitara K, et al. HERIZON-GEA-01. N Engl J Med. 2026;394:2002–2014. DOI: 10.1056/NEJMoa2517729 . 5. Ooki A, Shimozaki K, Yamaguchi K. Dynamic HER2 reassessment and precision sequencing after trastuzumab in HER2-positive advanced gastric cancer. ESMO Gastrointestinal Oncology. 2026. DOI: 10.1016/j.esmogo.2026.100349 . 6. Peng Z, et al. RELIGHT. J Clin Oncol. Published September 24, 2026. DOI: 10.1200/JCO-25-02933 . 7. Yan C, et al. DRAGON-01. JAMA Oncol. 2026;12(7):732–740. DOI: 10.1001/jamaoncol.2026.1347 . 8. Wang F, et al. Advances in therapeutic approaches to gastric cancer. CA Cancer J Clin. 2026;76(5):e70103. DOI: 10.3322/caac.70103 . 9. KEYNOTE-811 CPS≥1 analysis: https://www.keytrudahcp.com/efficacy/her2-positive-gastric-adenocarcinoma-keynote-811/ ; ASCO 2026 follow-up, DOI: 10.1200/JCO.2026.44.16_suppl.4040 . 10. 恒瑞医药，瑞拉芙普α批准信息，2026年1月8日：https://www.hengrui.com/media/detail-901.html 11. AstraZeneca. CLARITY-Gastric01 high-level results. July 27, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/sone-ve-improved-survival-in-gastric-cancers.html 12. CARsgen. Satri-cel approval announcement. June 22, 2026. https://www.carsgen.com/en/news/20260622/ 图片为原文献图形区域的截取，未改动曲线或数据。各图保留原图编号对应关系及来源；文中未来竞争分析属于Biotech前瞻基于现有证据的判断。

临床3期免疫疗法

2026-10-07

·PMLiVE

AstraZeneca and Daiichi Sankyo to collaborate with Summit Therapeutics

AstraZeneca and Daiichi Sankyo have entered into a clinical collaboration agreement with Summit Therapeutics to evaluate Datroway (datopotamab) in combination with ivonescimab across multiple tumour types including lung and breast cancers. The companies intend to begin with a phase 3 trial in 1st-line triple-negative breast cancer (TNBC). Datroway is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo. Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “Central to our strategy to transform cancer outcomes is harnessing the power of immunotherapy and antibody drug conjugate combinations to drive deeper, more durable responses. We believe the combination of Datroway and ivonescimab has the potential to make a meaningful difference in multiple tumour types including lung and breast cancers.” Maky Zanganeh, President and Co-Chief Executive Officer of Summit Therapeutics, said: “We believe this collaboration with Daiichi Sankyo and AstraZeneca reflects increasing conviction in ivonescimab’s potential as a foundational next-generation immunotherapy and advances our ambition for ivonescimab to become the global PD-1 / VEGF partner of choice for novel combinations.” John Tsai, Global Head, R&D, Daiichi Sankyo, said: “We are focused on maximising the potential of our DXd antibody drug conjugate portfolio through innovative combinations and strategic collaborations that support the continued advancement of our pipeline.” Under the terms of this agreement, each company will contribute their respective medicine for the planned combination trials, which will be sponsored by AstraZeneca or Daiichi Sankyo. AstraZeneca, Daiichi Sankyo and Summit will each contribute to trial costs and each company will retain development and commercial rights to their respective medicines. AstraZeneca also recently announced an equity investment that will help in part to support clinical collaborations evaluating combinations with ivonescimab including this agreement for Datroway, AstraZeneca’s separate agreement with Summit for combinations with sonesitatug vedotin (Sone-Ve), and planned future clinical collaborations intended to evaluate combinations with other AstraZeneca cancer medicines, including additional ADCs. Ivonescimab is a novel, potential first-in-class bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. The treatment is approved for certain patients with non-small cell lung cancer (NSCLC) in China, and a Biologics License Application (BLA) seeking approval in EGFR-mutated NSCLC is under review by the US FDA. Ivonescimab is currently being studied in phase 3 clinical trials in NSCLC, small cell lung cancer, biliary tract cancer, bladder cancer, TNBC, head and neck squamous cell carcinoma, colorectal cancer and pancreatic cancer.

免疫疗法临床3期上市批准抗体药物偶联物引进/卖出

100 项与 Sonesitatug vedotin 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D13164	-	-	-

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
食管腺癌	临床3期	美国	AstraZeneca PLC	2026-02-03
食管腺癌	临床3期	中国	AstraZeneca PLC	2026-02-03
食管腺癌	临床3期	日本	AstraZeneca PLC	2026-02-03
食管腺癌	临床3期	澳大利亚	AstraZeneca PLC	2026-02-03
食管腺癌	临床3期	奥地利	AstraZeneca PLC	2026-02-03
食管腺癌	临床3期	比利时	AstraZeneca PLC	2026-02-03
食管腺癌	临床3期	巴西	AstraZeneca PLC	2026-02-03
食管腺癌	临床3期	加拿大	AstraZeneca PLC	2026-02-03
食管腺癌	临床3期	法国	AstraZeneca PLC	2026-02-03
食管腺癌	临床3期	德国	AstraZeneca PLC	2026-02-03

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT06219941 (CLARITY-PT-01, ESMO_GI2026)	临床1期	胃癌三线 CLDN18.2-positive	31	Sonesitatug vedotin (CLDN18.2-positive)	窪蓋糧遞醖艱艱廠壓餘(觸壓築齋齋鬱憲艱鏇鬱) = 襯壓醖願顧襯襯艱範遞醖醖遞鑰醖憲鹽積繭糧 (衊廠範積願簾夢憲網遞 )	积极	2026-07-02
NCT04805307 (KYM901, Pubmed) 人工标引	临床1期	晚期胃癌 \| 胃食管交界处癌二线 CLDN18.2 Positive	134	CMG901	夢遞襯齋壓廠蓋醖簾窪(膚艱鑰顧鬱範鹹糧網願) = 膚齋齋獵壓顧鹹廠廠夢蓋遞遞積壓鹽網範範壓 (鏇鹽簾衊壓觸觸獵艱範, 21 ~ 39) 更多	积极	2025-01-06
				CMG901 (dose-escalation phase)	淵膚鬱網製廠顧繭顧窪(襯艱願鏇製壓憲鑰膚糧) = 壓獵夢鏇鑰觸襯願築構齋壓鬱糧鑰鏇廠醖築餘 (繭簾壓襯艱廠選願製願 )
NCT04805307 (KYM901, NEWS) 人工标引	临床1期	晚期胃癌	113	CMG901	選遞艱構鹽醖築築範繭(廠壓網衊餘餘蓋夢鹹淵) = 壓製鬱積網簾鬱鑰鑰簾觸廠遞廠壓糧繭齋鬱遞 (構範糧築襯積網夢鏇簾 ) 更多	积极	2024-06-03
				CMG901 (2.2 mg/kg)	選遞艱構鹽醖築築範繭(廠壓網衊餘餘蓋夢鹹淵) = 繭膚觸壓鑰襯衊觸鏇醖觸廠遞廠壓糧繭齋鬱遞 (構範糧築襯積網夢鏇簾 )
NCT04805307 (ASCO_GI2023) 人工标引	临床1期	CLDN18.2阳性胃食管交界处腺癌 \| CLDN18.2阳性胰腺癌 \| CLDN18.2阳性胃癌 CLDN18.2-positive	27	CMG901	觸廠衊選選壓範淵鹹齋(齋齋襯築遞獵夢獵範鹹) = 齋觸醖製繭顧鏇夢憲簾選糧鑰夢糧蓋繭齋鬱襯 (願膚簾鹹網衊醖築鬱範 )	积极	2023-01-24
				CMG901 (CLDN18.2-positive Gastric/GEJ Cancer)	膚餘蓋願鹽壓鬱襯衊選(構窪觸憲艱衊鏇鹽廠衊) = 襯顧獵範鏇夢鏇積膚網願鏇築顧網淵簾網艱鹽 (範蓋選襯築積簾選衊積 ) 更多