Phase II RAINSPOT: a Multicentric Open Label Trial of Zolbetuximab-Paclitaxel-Ramucirumab in Second Line Setting for CLDN18.2 Positive Gastro-esophageal Adenocarcinoma

This study examines whether adding the drug Zolbetuximab to an existing treatment (Paclitaxel and Ramucirumab) can improve patients' survival. The goal is to see if this combination works better for patients whose tumours contain a specific protein (CLDN18.2). The results will be compared to past patient data from those who only received the standard treatment.
Zolbetuximab (Vyloy) is a cancer medicine that is used to treat adults with gastric or gastro-esophageal junction adenocarcinoma (a type of cancer of the stomach or the transition between the stomach and esophagus). Zolbetuximab will be administered via an intravenous infusion in combination with Paclitaxel and Ramucirumab (Cyramza) (two other cancer drugs that are the standard treatment for this condition). Treatment will take place at regular intervals in the hospital. In addition to treatment,patients will undergo a tumour biopsy. While the biopsy procedure may cause some discomfort or pain, it will only be performed if medically justifiable. Patients participation in the study will continue as long as they receive treatment and the disease does not worsen. The overall duration of the study, for all patients, will span several years.

开始日期2025-10-01

申办/合作机构-

NCT06901531

/ Recruiting临床3期

A Phase 3, Double-blind, Randomized Study of Zolbetuximab in Combination With Pembrolizumab and Chemotherapy (CAPOX or mFOLFOX6) in First-line Treatment of Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma in Participants Whose Tumors Are HER2-negative, Claudin (CLDN) 18.2-positive and Programmed Death-ligand 1 (PD-L1)-Positive

Zolbetuximab is being studied in people with cancer in and around the stomach or where the food pipe (esophagus) joins the stomach, called gastroesophageal junction (GEJ) cancer. Zolbetuximab with chemotherapy may be used to treat stomach and GEJ cancer when the cancer cells do not have a protein called HER2 (human epidermal growth factor receptor 2) on their surface (HER2-negative) but do have a protein called Claudin 18.2 (Claudin 18.2-positive). Zolbetuximab is thought to work by attaching to the Claudin 18.2 protein in their tumor, which switches on the body's immune system to attack the tumor. Certain stomach and GEJ cancers may be treated with immunotherapy, which helps the body's immune system fight cancer. This study will give more information about how well zolbetuximab works when given with an immunotherapy medicine called pembrolizumab and chemotherapy. In this study, adults with stomach cancer or GEJ cancer will either be given zolbetuximab with pembrolizumab and chemotherapy or a placebo with pembrolizumab and chemotherapy. A placebo looks like zolbetuximab but doesn't have any medicine in it.
The main aim of the study is to check how long people with stomach cancer and GEJ cancer live after treatment with zolbetuximab with pembrolizumab and chemotherapy compared to placebo with pembrolizumab and chemotherapy.
Adults with locally advanced unresectable or metastatic stomach cancer or GEJ cancer can take part. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. A tumor sample (biopsy) of their cancer will have the Claudin 18.2 protein, PD-L1 protein, and be HER2-negative. They may have been previously treated with certain standard therapies. People cannot take part if they need to take medicines to suppress their immune system, have blockages or bleeding in their gut, have specific uncontrollable cancers such as symptomatic or untreated cancers in the nervous system, or have a specific heart condition, or infections.
The study treatments are either zolbetuximab with pembrolizumab and chemotherapy, or placebo with pembrolizumab and chemotherapy. People who take part will receive just 1 of the study treatments by chance. The people in the study and the study doctors will not know who takes which of the study treatments. Study treatment will be given in 6-week (42-day) cycles. The study treatment is mainly given to people slowly through a tube into a vein. This is called an infusion. People will receive study treatment as follows: Zolbetuximab or placebo: 1 infusion every 2 or 3 weeks (2 or 3 infusions in a cycle) together with: Chemotherapy (1 of the following types of chemotherapy): 1. CAPOX (capecitabine and oxaliplatin): 1 infusion of oxaliplatin every 3 weeks (2 infusions in a cycle). People will also take 1 tablet of capecitabine twice a day for 2 weeks (14 days) at the start of each cycle (Day 1) and again in the middle of each cycle (Day 22). After 8 study treatments people will receive capecitabine only. 2. Modified FOLFOX6 or mFOLFOX6 (5-fluorouracil, folinic acid and oxaliplatin): 1 infusion every 2 weeks (3 infusions in a cycle). After 12 study treatments people will receive folinic acid and fluorouracil only, instead of mFOLFOX6. Pembrolizumab: 1 infusion every 3 or 6 weeks (1 or 2 infusions in a cycle). People can be in the study and will receive study treatment until their cancer worsens, they cannot tolerate the study treatment, or they need to start another cancer treatment. People may receive pembrolizumab for up to 2 years. People will visit the clinic on certain days to receive their study treatment and have health checks. The study doctors will check if people had any medical problems from taking zolbetuximab or the other study treatments. On some visits they will have scans to check for any changes in their cancer. People will have the option of giving a tumor sample if they stop treatment because their cancer has worsened. People will visit the clinic after they stop their study treatment. People will be asked about any medical problems and will have a health check. People will continue to have scans every 9 or 12 weeks to check for any changes in their cancer. They will have telephone health checks every 3 months. The number of visits and checks done at each visit will depend on the health of each person and whether they completed their study treatment or not.

开始日期2025-05-22

申办/合作机构

Astellas Pharma Global Development, Inc.

NCT06881017

/ Not yet recruiting临床2期IIT

Establishment of Precision Targeted Therapy Strategies for Advanced Gastric Cancer Based on Novel Molecular Subtyping: an Umbrella Phase II Exploratory Clinical Study

This study is a prospective, umbrella-design, Phase II clinical trial. Eligible participants with advanced or metastatic gastric cancer who are treatment-naïve for advanced-stage systemic therapy will undergo biomarker profiling (HER2, CLDN18.2, and PD-L1) via next-generation sequencing (NGS) or immunohistochemistry (IHC). Participants will be stratified into distinct molecular subtypes and assigned subtype-specific therapeutic regimens. The primary objectives are to assess treatment efficacy (e.g., objective response rate) and safety profiles across molecularly defined cohorts.

开始日期2025-05-01

申办/合作机构

中国医科大学

100 项与佐妥昔单抗相关的临床结果

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100 项与佐妥昔单抗相关的专利（医药）

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114

项与佐妥昔单抗相关的文献（医药）

2025-06-01·EUROPEAN JOURNAL OF CANCER

Navigating the clinical challenges of zolbetuximab in patients with claudin positive advanced gastric cancer

Review

作者: Gervaso, L ; Fazio, N ; Cella, C A ; Rosanu, N M

Zolbetuximab, a first-in-class monoclonal antibody targeting Claudin 18.2 (CLDN 18.2), has demonstrated significant survival benefit when combined with chemotherapy in HER2-negative, CLDN 18.2-positive advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. However, its integration into clinical practice presents two major challenges: the best treatment selection between zolbetuximab or immune checkpoint inhibitor (ICI)-based regimens in patients co-expressing programmed death-ligand 1 (PD-L1), and the management of zolbetuximab-related nausea and vomiting (N/V). We critically reviewed evidence from randomized controlled trials, regulatory approvals, and recent expert consensus on zolbetuximab management. In CLDN 18.2-positive/PD-L1-positive patients, ICIs may offer greater long-term survival benefit especially in case of high PD-L1 CPS, while zolbetuximab may be preferred in patients with negative-to-low CPS or ICIs contraindications. N/V, reported in more than three-quarter of patients, is more frequent and severe during the first infusion, due to zolbetuximab loading dose and faster infusion rate. Proper management includes accurate adherence to high-risk antiemetic protocols (including NK-1/5-HT3 antagonists and corticosteroids) and careful control of infusion rates with a stop and go strategy. In case of CLDN 18.2 and PD-L1 CPS co-positivity, we advocate the use of PD-L1 CPS ≥ 10 as a practical decision-making threshold for favoring ICI-based regimens. However, the treatment selection should be tailored on comorbidities, comprehensive molecular characterization and available subsequent options. To ensure the optimal use of zolbetuximab, special attention is required during the first cycle, due to higher risk of infusion-related N/V. We suggest that the optimization of both prophylactic and on-treatment antiemetic strategies is essential to enhance zolbetuximab adherence and maximize clinical outcomes.

2025-05-30·Oncology Research and Treatment

Guidelines of Onkopedia: What is new? Esophageal Cancer.

Review

作者: Moehler, Markus ; Lorenzen, Sylvie ; Thuss-Patience, Peter ; Götze, Thorsten O ; Köberle, Dieter ; Stuschke, Martin ; Grenacher, Lars ; Porschen, Rainer ; Gockel, Ines ; Wörmann, Bernhard ; Scheck, Magdalena K ; Al-Batran, Salah-Eddin ; Pritzkuleit, Ron ; Maschmeyer, Georg ; Sinn, Marianne ; Hass, Holger G ; Rumpold, Holger ; Borner, Markus

This article presents new relevant aspects of the recently updated German, Swiss, Austrian Onkopedia guideline for the treatment of esophageal cancer. The full guideline can be accessed at https://www.onkopedia-guidelines.info/en/onkopedia/guidelines/esophageal-cancer/@@guideline/html/index.html. All rights for the use of text sections and Figures have been obtained. The most important aspects in the perioperative treatment of resectable esophageal adenocarcinoma include the recommendation for the use of perioperative chemotherapy with FLOT as it was shown superior to preoperative chemoradiotherapy analogous CROSS in the ESOPEC trial. Furthermore, there is increasing evidence for the effectivity of targeting therapy and immune checkpoint inhibition in certain molecular defined subgroups. Immune checkpoint inhibition is recommended in combination with perioperative chemotherapy (FLOT) for MSI-H tumors, whereby the treatment should preferably take place in studies. In the metastatic setting, the approval for the PD-1 inhibitor tislelizumab was extended to the first-line treatment of both, squamous cell- and adenocarcinoma of the esophagus (TAP score (≥ 5%) and for second line for squamous-cell cancer only (independent of PD-L1 expression). Moreover, for gastroesophageal junction (GEJ) tumors, pembrolizumab is available upon PD-L1 expression (CPS ≥ 1) according to the data of the KEYNOTE-859 trial. In addition to the established biomarkers HER2 und PD-L1, Claudin 18.2 represents now a new targetable option. First-line chemotherapy is to be combined with zolbetuximab in Claudin 18.2 positive GEJ tumors. For biomarker-negative adenocarcinomas of the esophagus and esophago-gastric junction (GEJ), a modified triplet regimen (TFOX) is a newly presented treatment option. Because of high toxicity rates and yet unclear survival benefit this option is only recommended for docetaxel-naïve patients with high remission pressure.

2025-05-05·MOLECULAR PHARMACEUTICS

Targeted Radionuclide Therapy of CLDN18.2-Positive Gastric Cancer with [¹³¹I]I-Zolbetuximab: An In Vitro and In Vivo Study

Article

作者: Liu, Yuxia ; Li, Qingnuan ; Wang, Yang ; Ma, Lin ; Mu, Chao ; Yang, Jian ; He, Shuhua ; Li, Zheng ; Kuang, Zijun

Radiopharmaceuticals are a promising therapeutic strategy for tumors with less reduced resistance and minimal side effects. In our previous study, we radiolabeled the monoclonal antibody zolbetuximab, which targets CLDN18.2, with ¹²⁵I, and the labeled compound showed favorable tumor targeting and retention. In this research article, [¹³¹I]I-zolbetuximab was prepared to investigate its therapeutic effect on gastric cancer using in vitro and in vivo studies. The zolbetuximab was radiolabeled with ¹³¹I using the Iodogen method. The uptake mechanism of [¹³¹I]I-zolbetuximab was investigated through an endocytosis experiment using MKN45-CLDN18.2 and MKN45 cells. The safety assessment of [¹³¹I]I-zolbetuximab was conducted in normal mice using hematoxylin/eosin (H&E) staining. The tumor uptake, biodistribution, and therapeutic efficacy of [¹³¹I]I-zolbetuximab were evaluated in nude mice bearing MKN45-CLDN18.2 tumors, while the hematological analysis, immunohistochemistry, Western blotting (WB), immunofluorescence, and H&E assays were used to further assess the treatment response and toxicity. [¹³¹I]I-Zolbetuximab exhibited a high labeling efficiency of (96.05 ± 0.23)%, a specific activity of 1.75 × 10² GBq/μmol, and good in vitro stability. The binding of [¹³¹I]I-zolbetuximab to the membrane surface receptors of MKN45-CLDN18.2 cells resulted in significant tumor uptake, retention, and favorable biodistribution in CLDN18.2-positive tumor-bearing nude mice. Safety assessments, including H&E staining, indicated no significant damage to normal mouse organs caused by the labeled compounds. In a therapeutic study involving MKN45-CLDN18.2 tumor-bearing nude mice, increasing drug dose led to notable enhancements in therapeutic efficacy and survival rates. H&E staining of mouse organs at the end of treatment showed no significant toxicity was observed across all dose groups throughout the treatment period. Furthermore, immunohistochemistry, immunoblotting, and immunofluorescence analyses conducted on mouse tumors at the treatment end point demonstrated a reduction in CLDN18.2 expression following treatment. Altogether, [¹³¹I]I-zolbetuximab displayed exceptional targeting capability, tumor retention property, significant therapeutic efficacy, and safety. These findings suggest its potential to serve as a targeted radiopharmaceutical for the treatment of CLDN18.2-positive gastric cancer.

328

项与佐妥昔单抗相关的新闻（医药）

2025-06-12

·生物制品圈

Claudins 与癌症：从细胞屏障到精准治疗的新靶点

摘要：Claudins 是一类构成细胞紧密连接的跨膜蛋白家族，在维持细胞屏障功能、离子交换和细胞迁移中起关键作用。当 Claudins 的表达或功能异常时，会促进癌症的侵袭与转移，例如在胃癌、乳腺癌和结直肠癌中，特定 Claudins 的过表达与肿瘤恶性程度及不良预后密切相关。近年来，针对 Claudins 的靶向治疗取得显著进展，如靶向 Claudin 18.2 的单克隆抗体联合化疗已在胃肠癌中显示出疗效，CAR-T 细胞疗法也在临床试验中展现潜力。本文将系统解析 Claudins 的生物学功能、在癌症中的异常调控机制，并展望其作为治疗靶点的未来前景，为理解癌症发生发展及精准治疗提供新视角。一、Claudins：细胞屏障的 “建筑师”1.1 紧密连接的核心组件人体细胞间的 “防火墙”——紧密连接（TJs），由 Claudins、occludin 和 tricellulin 等蛋白共同构成，其中 Claudins 是决定屏障选择性的关键分子。这类蛋白含有四个跨膜结构域，通过胞外环形成 “孔道” 或 “屏障”，控制离子和水分子的通过 [图 1]。例如，Claudin 5 作为 “屏障型” 蛋白，可密封细胞间隙，而 Claudin 15 则形成 “通道型” 结构，允许阳离子通过。1.2 动态调控的生理功能Claudins 的功能并非一成不变：它们的半衰期短至 4 小时（如 Claudin 4），通过快速更新维持屏障动态平衡。在肾脏中，Claudin 16 和 19 协同调控镁离子重吸收；在胃肠道，Claudin 2 形成阳离子通道，参与水分代谢。这种精准调控一旦失衡，便可能为癌症滋生埋下隐患。二、Claudins 的 “叛变”：癌症进展的推手2.1 组织特异性表达的紊乱正常组织中，Claudins 呈现严格的组织特异性表达（表 1）。例如，Claudin 18.2 仅在胃黏膜上皮细胞表达，而在胃癌中，其异常表达可促进肿瘤细胞与癌相关成纤维细胞的相互作用，加速转移。在乳腺癌中，Claudin 3/4 的过表达与雌激素受体（ER）阴性、HER2 阳性亚型相关，预示更具侵袭性的表型。2.2 促癌机制：从信号紊乱到转移 “帮凶”上皮 - 间质转化（EMT）：Claudin 1 在肝癌中通过激活 c-Abl/Raf/ERK 通路诱导 EMT，使上皮细胞获得迁移能力；化疗耐药：Claudin 1 在结直肠癌中通过上调 EPHA2 酪氨酸激酶，增强 AKT 信号，导致 5 - 氟尿嘧啶耐药；免疫微环境重塑：卵巢癌中 Claudin 6 的高表达与树突状细胞、NK 细胞浸润负相关，营造免疫抑制环境。三、Claudins 调控的 “黑匣子”3.1 基因与表观遗传的双重操控转录因子干预：Slug 和 Snail 转录因子可抑制 Claudin 1 的 mRNA 表达，在乳腺癌中促进细胞侵袭；DNA 甲基化：胃癌中 Claudin 11 启动子的高甲基化导致其表达沉默，与幽门螺杆菌感染及肿瘤进展相关；组蛋白修饰：卵巢癌中 Claudin 3/4 的过表达与 H3K27me3 等抑制性甲基化丢失有关。3.2 配体与信号通路的串扰雌激素通过 ERβ 调控 Claudin 6 的表达，在乳腺癌中抑制细胞迁移；而在子宫内膜癌中，ERα 却通过 Claudin 6 促进肿瘤生长。这种矛盾性揭示了 Claudins 调控的复杂性。四、靶向 Claudins：从实验室到临床的突破4.1 单克隆抗体：精准 “狙击”Zolbetuximab（IMAB362）：靶向 Claudin 18.2 的 IgG1 抗体，在 III 期 SPOTLIGHT 试验中，联合 mFOLFOX6 使胃肠癌患者无进展生存期（PFS）延长至 10.61 个月，较安慰剂组提高近 2 个月；Claudin 4 靶向抗体：KM3900 抗体可通过抗体依赖细胞毒性（ADCC）杀伤胰腺癌细胞，且对正常细胞无明显毒性。4.2 细胞疗法：CAR-T 的新战场Claudin 18.2 特异性 CAR-T 细胞在 I 期临床试验中展现疗效，客观缓解率（ORR）达 48.6%，疾病控制率（DCR）73.0%，为胃肠癌患者带来希望。此外，mRNA 疫苗联合 CAR-T（如 BNT211）可增强 T 细胞扩增，在 Claudin 6 阳性实体瘤中 ORR 达 33%。4.3 抗体 - 药物偶联物（ADC）：“生物导弹” 的升级针对 Claudin 6 的 ADC 药物（如 CLDN6-23-ADC）在临床前模型中显示出对生殖细胞肿瘤的选择性杀伤，为卵巢癌和睾丸癌治疗提供新思路。五、挑战与未来：Claudins 靶向治疗的 “双刃剑”5.1 临床应用的瓶颈异质性难题：胃癌中 Claudin 18.2 的表达异质性导致部分患者对 Zolbetuximab 无响应；免疫原性风险：CAR-T 治疗中，针对 Claudin 18.2 的 CAR 结构可能引发细胞因子释放综合征（CRS）；正常组织毒性：Claudin 18.2 在正常胃黏膜的表达可能限制药物剂量提升。5.2 破局之路：联合策略与精准诊断联合免疫治疗：Zolbetuximab 与 PD-1 抑制剂联用的 ILUSTRO 试验正在探索中，有望克服免疫抑制微环境；液体活检：血液中 Claudin 4 的检测可作为胰腺癌转移的标志物，辅助疗效监测；AI 辅助靶点筛选：通过机器学习分析 Claudin 表达与免疫细胞浸润的关联，优化患者分层。六、结语：Claudins 研究的里程碑与新征程从 1998 年 Claudin 1 的发现，到如今 Zolbetuximab 获批 III 期临床试验，Claudins 已从基础研究的 “冷门” 靶点，成长为精准治疗的 “热门” 方向。尽管挑战重重，但其在肿瘤特异性表达和功能中的核心地位，使其成为破解癌症转移和耐药的关键钥匙。未来，随着单细胞测序、AI 药物设计等技术的融入，Claudins 靶向治疗或将开启实体瘤个体化治疗的新篇章。识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

细胞疗法免疫疗法临床研究信使RNA

2025-06-10

·氨基观察

安斯泰来，“颠覆”安斯泰来

氨基观察-创新药组原创出品作者 | 郑晓5月末，CLDN18.2赛道迎来了久违的一笔交易。信诺维宣布，与安斯泰来达成合作协议，后者获得CLDN18.2 ADC药物XNW27011全球（除大中华区）开发权益。这笔交易，价格不菲。根据协议条款，信诺维将获得1.3亿美元的首付款，并有资格收取最高7000万美元的近期付款，以及最高可达13.4亿美元的里程碑付款。也就是说，信诺维能够获得的近期付款总额，将高达2亿美元。而XNW27011目前还仅在中国开展1/2期临床研究。某种程度上，这也体现出安斯泰来对于CLDN18.2赛道的高度重视。毕竟，CLDN18.2 ADC领域已经竞争相对激烈，并且大力押注早期分子似乎并非一个好选择。此前，包括石药集团在内的CLDN18.2 ADC，虽然国内临床数据惊艳，但在海外却难以复制。不过，安斯泰来可能没有太多选择。其CLDN18.2单抗zolbetuximab，虽然已经在全球包括美国在内的多个国家、地区获批上市，但是药物局限性明显。面对来势汹汹的入局者，安斯泰来只能被迫押注，“颠覆”自己，来谋求在CLDN18.2赛道更好地活下去。/ 01 /不完美的FICCLDN18.2赛道的热度，某种程度上是由安斯泰来带起来的。2016年10月29日，安斯泰来宣布以14亿美元收购德国生物技术公司Ganymed，看中的便是CLDN18.2单抗zolbetuximab。此后研发虽历经波折，但zolbetuximab最终撞线。2024年10月，其获得FDA认可，获批上市。Zolbetuximab的一小步，是属于CLDN18.2靶点的一大步。但遗憾的是，虽然zolbetuximab迈出了第一步，却因为自身分子的缺陷，为后来者留下了巨大的超车空间。Zolbetuximab的两项Ⅲ期临床试验SPOTLIGHT和 GLOW，都达到了主要临床终点，但与对照组相比效果相对有限，PFS获益不超2个月，OS获益不超3个月。具体来说，SPOTLIGHT（联合mFOLFOX6——奥沙利铂、亚叶酸+氟尿嘧啶联合方案）治疗组的中位PFS为10.61个月，中位OS为18.23个月，比安慰剂组多1.94个月和2.69个月。GLOW（联合CAPOX——卡培他滨+奥沙利铂）治疗组的中位PFS为8.21个月，中位OS为14.39个月，比安慰组多1.41个月和2.23个月。而且，zolbetuximab的Ⅲ期临床均是在CLDN18.2高表达（≥75%）的患者中进行，对其他患者作用不明显。这注定了其临床使用会受限。在所有实体瘤中，CLDN18.2高表达患者仅占33%—37%。而在患者群体规模最大的胃癌领域，高表达患者占比更是仅有20%左右。毫无疑问，虽然zolbetuximab以一己之力开启了CLDN18.2时代，但是CLDN18.2的时代却不一定属于zolbetuximab。这也是为什么，安斯泰来在已经拥有FIC的情况下，选择引进早期分子XNW27011。/ 02 /弥补Z药的遗憾看起来，安斯泰来是希望通过XNW27011，来弥补zolbetuximab的遗憾。作为一款ADC分子，XNW27011瞄准的是CLDN18.2低表达人群。根据其在ASCO上更新的数据显示，在75例可评估的CLDN18.2阳性（≥5%肿瘤细胞，IHC≥2+）G/GEJ AC患者中，取得了46.7%的最佳总体缓解（BOR），疾病控制率（DCR）达到了88.0%。对于这起合作，安斯泰来也特意强调，XNW27011有潜力满足当前未被满足的患者需求。当然，XNW27011是否能够如安斯泰来所愿，还不得而知。信诺维方面表示，因为被安斯泰来引进之后涉及到保密协议，一些关键信息并没有透露。例如，公司没有透露确认的ORR是多少，以及在Claudin18.2表达水平远低于75%的患者中是否真的观察到任何活性。两大关键信息的缺失，使得市场对XNW27011的竞争力还不得而知。与此同时，安全性问题也是安斯泰来需要继续探索的。此前公布的ASCO摘要中指出，3.0mg/kg剂量下出现了一例治疗相关的肺炎死亡，不过在后续更新的海报中没有提及此事，公司表示这与XNW27011无关。总体来说，XNW27011是否能够让安斯泰来复制zolbetuximab上岸的幸运，还需要时间给出答案。就现在来看，显然只是一场豪赌。/ 03 /豪赌与未来鉴于CLDN18.2的突出前景，竞争已经空前激烈。这也导致，入局者必须拿出更好的成绩，才有希望脱颖而出。3月20日，Elevation宣布决定终止开发其CLDN18.2 ADC药物EO-3021。EO-3021是由Elevation于2022年7月从石药集团引进，并支付了2700万美元预付款、11.5亿美元里程碑金额及一定比例的销售分成。然而，如今的Elevation得出结论，EO-3021与其他靶向CLDN18.2的ADC相比没有竞争力，只能遗憾退出。而在宣布终止研发EO-3021消息后不到3个月，Elevation迎来了被收购的结局。日前，Elevation宣布接受了对冲基金Tang Capital Partners旗下投资公司Concentra的收购要约。后者将以每股0.36美元的现金收购Elevation的股票，整体估值在2200万美元左右。事实上，EO-3021只是CLDN18.2 ADC折戟的一个缩影。此前。礼新医药的LM-302也遭遇了百时美施贵宝的退货。这表明CLDN18.2 ADC研发不易。而到如今，CLDN18.2 ADC需要竞争的，也不只是ADC本身，甚至是TCE/CLDN18.2双抗、CLDN18.2/4-1BB双抗等诸多不同路线。当一个靶点过于火热，被革命的不只是FIC本身，还有包括许多后来者。对于火热的CLDN18.2 靶点来说，未来到底属于谁，还不得而知。PS：欢迎扫描下方二维码，添加氨基君微信号交流。

临床3期抗体药物偶联物并购上市批准临床2期

2025-06-06

·FiercePharma

Fierce Pharma Asia—Bispecific field's roller coaster week; Enhertu's first-line win; Regeneron-Hansoh obesity deal

Summit Therapeutics' unsatisfactory global phase 3 readout, Bristol Myers Squibb's big bet on PD-L1/VEGF, Enhertu's first-line breast cancer data and Regeneron's obesity deal with Hansoh Pharma made our news this week. The PD-(L)1xVEGF field had a roller coaster week marked by an imperfect readout and a potentially $11 billion deal. AstraZeneca and Daiichi Sankyo trotted out Enhertu's detailed data in first-line breast cancer. Regeneron signed on a GLP-1/GIP candidate from China's Hansoh Pharma. And more.1. Akeso, Summit's ivonescimab delayed progression of certain lung cancers in first global phase 3 readoutBristol Myers inks $11B BioNTech deal to join bispecific gold rush, leaping ahead of Merck and PfizerSummit Therapeutics unveiled the first global phase 3 readout from Akeso’s PD-1xVEGF bispecific ivonescimab, saying the drug reduced the risk of progression or death by 48% in previously treated EGFR-mutated nonsquamous non-small cell lung cancer. But, because the HARMONi trial did not meet the overall survival endpoint at the current analysis, the company’s stock price tanked.But the PD-(L)1xVEGF field quickly got an injection of confidence when Bristol Myers Squibb announced a potentially $11.1 billion deal to co-develop and co-commercialize BioNTech’s PD-L1xVEGF candidate BNT327. The deal includes $1.5 billion upfront and $2 billion in unconditional anniversary payments through 2028. BioNTech got the drug recently from purchasing its then-partner, Chinese biotech Biotheus, for $800 million upfront.2. ASCO: AstraZeneca, Daiichi flex Enhertu's muscles in first-line breast cancer as they drop new phase 3 gastric cancer dataAstraZeneca and Daiichi Sankyo’s Enhertu, used in combination with Roche’s Perjeta, significantly reduced the risk of progression or death by 44% versus the standard THP regimen in first-line HER2-positive breast cancer. Experts suggested that the result, from the Destiny-Breast09 trial, makes the Enhertu combo a new first-line standard treatment option, although some questions such as treatment duration remained.3. Regeneron pens $2B pact for Hansoh's potential obesity rival to Lilly's ZepboundRegeneron is paying China’s Hansoh Pharma $80 million upfront for ex-China rights to a GLP-1/GIP receptor agonist coded HS-20094. The deal includes up to $1.93 billion in potential milestone payments. The drug is currently undergoing a phase 2b in diabetes and a phase 3 in obesity in China.4. Astellas aspires to strike CLDN18.2 gold again with ADC licensing deal worth up to $1.34BAstellas has doubled down on the Claudin18.2 field by in-licensing an antibody-drug conjugate from Chinese biotech Evopoint Biosciences in a deal potentially worth up to $1.34 billion. Evopoint is testing the agent, XNW27011, in a phase 1/2 solid tumor trial covering gastric, pancreatic, colorectal, ovarian and other cancers. Astellas already has the first FDA-approved Claudin18.2 agent, Vyloy.5. Cullinan pens $700M pact for BCMA bispecific to pair with another autoimmune T-cell engagerCullinan Therapeutics, which is already working on a CD19 bispecific for autoimmune diseases, is getting a BCMA T-cell engager. For $20 million upfront and nearly $700 million in potential milestones, Cullinan is getting ex-China rights to Genrix Bio’s BCMAxCD3 candidate velinotamig. Last year, researchers reported a deep remission in a woman with aggressive refractory systemic lupus erythematosus who received Johnson & Johnson’s BCMA bispecific Tecvayli.6. Kelun-Biotech raises $250M with 6M share placement (release)After its Hong Kong IPO in 2023, China's Kelun-Biotech has raised about $250 million in a new share placement. The company sold about 5.92 million shares at HK$331.80 per share, according to a press release. Kelun said the placement was "multiple times oversubscribed" with support from various types of investors, leading the biotech to expand a previous fundraising target of $200 million. Kelun plans to use the money to fund R&D operations, regulatory interactions, manufacturing infrastructure and more. Other News of Note:7. Ascletis scores phase 3 win for daily acne pill, prepares push to Chinese regulators8. ASCO: Kura, Kyowa reveal 23% remission rate behind oral leukemia drug's phase 2 win9. BioAge inks option agreement for Chinese biotech's obesity asset on heels of earlier APJ agonist setback10. Astellas organizes action week to connect patients to advocacy groups11. Fujifilm, Coherus, ViGeneron unveil rebrands to better reflect ongoing work

临床3期临床2期上市批准临床结果引进/卖出

100 项与佐妥昔单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	佐妥昔单抗	-	DB15118

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
晚期胃食管交界处腺癌	加拿大	Astellas Pharma Canada, Inc.	2025-01-09
CLDN18.2阳性胃食管交界处腺癌	英国	Astellas Pharma, Inc.	2024-08-14
CLDN18.2阳性胃腺癌	英国	Astellas Pharma, Inc.	2024-08-14
CLDN18.2阳性胃癌	日本	Astellas Pharma, Inc.	2024-03-26

未上市

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
局部晚期胃食管交界处腺癌	临床3期	美国	Astellas Pharma Global Development, Inc.	2018-11-28
局部晚期胃食管交界处腺癌	临床3期	中国	Astellas Pharma Global Development, Inc.	2018-11-28
局部晚期胃食管交界处腺癌	临床3期	日本	Astellas Pharma Global Development, Inc.	2018-11-28
局部晚期胃食管交界处腺癌	临床3期	阿根廷	Astellas Pharma Global Development, Inc.	2018-11-28
局部晚期胃食管交界处腺癌	临床3期	加拿大	Astellas Pharma Global Development, Inc.	2018-11-28
局部晚期胃食管交界处腺癌	临床3期	克罗地亚	Astellas Pharma Global Development, Inc.	2018-11-28
局部晚期胃食管交界处腺癌	临床3期	希腊	Astellas Pharma Global Development, Inc.	2018-11-28
局部晚期胃食管交界处腺癌	临床3期	爱尔兰	Astellas Pharma Global Development, Inc.	2018-11-28
局部晚期胃食管交界处腺癌	临床3期	马来西亚	Astellas Pharma Global Development, Inc.	2018-11-28
局部晚期胃食管交界处腺癌	临床3期	荷兰	Astellas Pharma Global Development, Inc.	2018-11-28

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临床结果

适应症

分期

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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


NCT03504397 (SPOTLIGHT \| SPOTLIGHT study, CTgov)	临床3期	-	565	folinic acid+zolbetuximab+oxaliplatin+fluorouracil	蓋襯夢鏇憲觸選範選夢(鏇衊鑰鏇選築鹽鹹壓鑰) = 範遞蓋膚繭鑰壓鹹鏇衊鏇鏇願壓構鬱鹽壓觸願 (築廠糧繭膚構憲遞構觸, 網獵壓範襯製衊鏇遞遞 ~ 壓繭夢鬱鬱窪繭窪繭簾) 更多	-	2025-02-26
NCT03653507 (GLOW, CTgov)	临床3期	局部晚期胃食管交界处腺癌 \| 转移性胃食管结合部腺癌	507	CAPOX+Zolbetuximab (CAPOX+ Zolbetuximab)	廠醖鹹衊憲鏇觸鏇網憲(構齋齋鬱糧淵鹹網選廠) = 衊鹹鑰鑰醖鬱顧淵鏇顧鹹壓蓋廠壓蓋遞製願夢 (選積夢簾遞憲積蓋膚廠, 餘齋鬱鏇築獵獵鏇廠顧 ~ 構獵選遞壓選鏇網願觸) 更多	-	2025-01-27
				Placebo (CAPOX+ Placebo)	廠醖鹹衊憲鏇觸鏇網憲(構齋齋鬱糧淵鹹網選廠) = 壓壓構鹹遞鬱獵遞選襯鹹壓蓋廠壓蓋遞製願夢 (選積夢簾遞憲積蓋膚廠, 觸網齋鬱構壓鏇願簾壓 ~ 築鹹憲鑰憲壓簾鏇艱齋) 更多
NCT03653507 (GLOW, NEWS) 人工标引	临床3期	胃癌 \| 胃食管交界处腺癌一线 HER2 Negative \| CLDN18.2 Positive	145	佐妥昔单抗联合CAPOX	範願憲膚廠獵構網構夢(遞鹽鹽齋簾觸艱齋廠顧) = 蓋鑰選願壓餘獵餘夢壓鹽築觸壓積鏇鑰鏇鑰鹹 (餘構願繭淵鹽製獵鑰鏇, 6.1 ~ 9.1) 更多	积极	2024-09-28
				安慰剂联合CAPOX	範願憲膚廠獵構網構夢(遞鹽鹽齋簾觸艱齋廠顧) = 糧繭艱襯壓淵鏇蓋遞繭鹽築觸壓積鏇鑰鏇鑰鹹 (餘構願繭淵鹽製獵鑰鏇, 5.0 ~ 8.0) 更多
NCT03504397 (SPOTLIGHT, NEWS) 人工标引	临床3期	胃食管交界处腺癌一线 CLDN18.2 Positive \| HER2 Negative	61	佐妥昔单抗+mFOLFOX6	簾蓋衊餘衊製壓鏇簾選(選憲網餘選簾範衊積獵) = 窪簾獵網餘憲積餘衊蓋憲鏇衊夢鹽範繭積憲窪 (網憲襯構顧鑰鹹鹹蓋鏇, 6.7 ~ 16.7) 更多	积极	2024-09-28
				安慰剂+mFOLFOX6	簾蓋衊餘衊製壓鏇簾選(選憲網餘選簾範衊積獵) = 遞憲觸繭簾醖簾鏇襯願憲鏇衊夢鹽範繭積憲窪 (網憲襯構顧鑰鹹鹹蓋鏇, 6.0 ~ 8.4) 更多
NCT03653507 \| NCT03504397 (SPOTLIGHT \| GLOW, ESMO2024)	临床3期	CLDN18.2阳性胃食管交界处腺癌一线 CLDN18.2+ \| HER2-	1,072	Zolbetuximab + chemotherapy	衊窪醖選積窪壓齋憲鏇(醖製廠繭簾築鹹遞築觸) = 遞憲壓築網鹹壓遞窪襯壓鬱築鹽衊選構觸糧願 (壓壓網齋餘構廠範鬱糧, 8.4 ~ 10.4) 更多	积极	2024-09-16
				Placebo + chemotherapy	衊窪醖選積窪壓齋憲鏇(醖製廠繭簾築鹹遞築觸) = 窪壓衊餘醖網襯簾餘蓋壓鬱築鹽衊選構觸糧願 (壓壓網齋餘構廠範鬱糧, 7.6 ~ 8.4) 更多
NCT03504397 (SPOTLIGHT, ASCO2024) 人工标引	临床3期	CLDN18.2阳性胃食管交界处腺癌 \| CLDN18.2阳性胃癌一线 HER2 Negative \| CLDN18.2 Positive	565	Zolbetuximab + mFOLFOX6	夢糧鏇廠遞顧淵醖襯鹽(繭遞憲積衊顧憲選齋鏇) = 觸鹹糧顧選鹹顧構壓齋壓齋窪選艱鹹壓廠願鑰 (選醖衊艱醖鹹糧壓廠醖 ) 更多	积极	2024-05-24
				Placebo + mFOLFOX6	夢糧鏇廠遞顧淵醖襯鹽(繭遞憲積衊顧憲選齋鏇) = 艱鏇襯襯範窪餘壓衊膚壓齋窪選艱鹹壓廠願鑰 (選醖衊艱醖鹹糧壓廠醖 ) 更多
NCT03653507 \| NCT03504397 (Pubmed \| Future Oncol)	临床3期	胃食管交界处癌 CLDN18.2-positive \| HER2-negative	-	Zolbetuximab plus chemotherapy	鹹鹽構觸願壓齋積壓鬱(艱淵夢窪齋繭夢蓋襯襯) = 膚構餘鹽衊膚鑰顧襯醖構窪壓製鹽鏇範壓襯鏇 (觸繭範鏇網遞範網糧鑰 ) 更多	积极	2024-05-24
				Placebo plus chemotherapy	鹹鹽構觸願壓齋積壓鬱(艱淵夢窪齋繭夢蓋襯襯) = 鏇獵襯選膚膚夢顧遞願構窪壓製鹽鏇範壓襯鏇 (觸繭範鏇網遞範網糧鑰 ) 更多
NCT04086758 \| NCT03653507 \| NCT00909025 \| NCT03504397 \| NCT03505320 \| NCT01630083 \| NCT03528629 \| NCT01197885 \| NCT01671774 (ASCO_GI2024) 人工标引	N/A	食管腺癌 \| CLDN18.2阳性胃食管交界处腺癌 \| CLDN18.2阳性胃腺癌一线 CLDN18.2 Positive	-	Zolbetuximab (First Dose (800 mg/m2))	鹽醖膚餘鏇糧網餘膚鬱(築醖襯鏇簾積艱選廠窪) = 蓋鹹鏇獵鹽窪鏇範築遞衊積構醖鹹積蓋艱範衊 (醖鏇鏇鏇範願憲廠膚蓋, 96) 更多	积极	2024-01-18
				Zolbetuximab (Steady State (600 mg/m2 Q3W))	鹽醖膚餘鏇糧網餘膚鬱(築醖襯鏇簾積艱選廠窪) = 壓簾遞壓淵夢獵淵鹹齋衊積構醖鹹積蓋艱範衊 (醖鏇鏇鏇範願憲廠膚蓋, 91) 更多
NCT03653507 \| NCT03504397 (SPOTLIGHT, ASCO_GI2024) 人工标引	临床3期	胃腺癌 \| 胃食管交界处腺癌一线 HER2 Negative \| CLDN18.2 Positive	-	Zolbetuximab + mFOLFOX6	網齋窪願蓋衊築積獵憲(繭襯製廠糧蓋艱構遞襯) = 壓憲鹽壓醖襯衊願鹽蓋鏇構蓋憲襯築衊膚繭範 (廠醖網窪艱醖獵獵顧齋 ) 更多	积极	2024-01-18
				Zolbetuximab + CAPOX	網齋窪願蓋衊築積獵憲(繭襯製廠糧蓋艱構遞襯) = 鹽齋壓鬱鑰糧壓選範顧鏇構蓋憲襯築衊膚繭範 (廠醖網窪艱醖獵獵顧齋 ) 更多
GLOW study (ESMO_ASIA2023)	临床3期	CLDN18.2阳性胃食管交界处腺癌一线 CLDN18.2+ \| HER2−	507	Zolbetuximab + CAPOX	艱鬱鏇鬱廠襯構獵顧顧(範範憲製範齋遞築壓夢) = 鑰觸顧淵製獵憲構繭選窪鬱廠艱顧衊獵鹹襯餘 (窪鹽廠窪淵選餘顧製餘 ) 更多	积极	2023-12-03
				Placebo + CAPOX	艱鬱鏇鬱廠襯構獵顧顧(範範憲製範齋遞築壓夢) = 醖構構夢夢範糧鹹願鬱窪鬱廠艱顧衊獵鹹襯餘 (窪鹽廠窪淵選餘顧製餘 ) 更多