多塔利单抗(Dostarlimab-gxly) - 药物靶点：PD-1_在研适应症：晚期子宫内膜癌，复发性子宫内膜癌，MMRD实体瘤_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Dostarlimab、Immunoglobulin G4, anti-programmed cell death protein 1 (PDCD1) (humanized clone ABT1 gamma4-chain), disulfide with humanized clone ABT1 kappa-chain, dimer、多斯塔利单抗

+ [10]

靶点

PD-1

作用方式

抑制剂

作用机制

PD-1抑制剂(细胞程序性死亡-1抑制剂)

治疗领域

肿瘤泌尿生殖系统疾病神经系统疾病+ [8]

在研适应症

晚期子宫内膜癌复发性子宫内膜癌MMRD实体瘤+ [82]

非在研适应症

晚期胆管癌透明细胞肉瘤妊娠滋养细胞疾病+ [4]

原研机构

AnaptysBio, Inc.

在研机构

Tesaro, Inc.

GSK PlcGlaxoSmithKline Research & Development Ltd.

+ [7]

非在研机构-

权益机构

AnaptysBio, Inc.Sagard Healthcare Royalty Partners LP

GSK Plc

+ [1]

最高研发阶段批准上市

首次获批日期

欧盟 (2021-04-21),

MSI-H 子宫内膜癌错配修复缺陷子宫内膜癌

最高研发阶段(中国)临床3期

特殊审评优先审评 (美国)、快速通道 (美国)、优先审评 (澳大利亚)、加速批准 (美国)、突破性疗法 (美国)

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结构/序列

Sequence Code 315609369H

来源: *****

Sequence Code 315609370L

来源: *****

关联

98

项与多塔利单抗相关的临床试验

NCT06879717

/ Recruiting临床1/2期

A Phase I/IIa Study of Roginolisib in Combination With Dostarlimab With or Without Docetaxel in Patients With Advanced Non-squamous NSCLC Who Have Progressed on Standard of Care Immune Checkpoint Therapy and Platinum Doublet Chemotherapy or Standard Immunotherapy Without Chemotherapy (PULMO-1)

The goal of this clinical trial is to learn how roginolisib works in combination with dostarlimab with or without docetaxel in adult patients with advanced non small-cell lung cancer. The main questions it aims to answer are:
To compare across the treatment arms the proportion of patients with a reduction in Treg cells To evaluate the safety and tolerability of roginolisib plus dostarlimab, with or without docetaxel

开始日期2025-04-22

申办/合作机构

iOnctura SA

NCT06897527

/ Not yet recruiting临床4期

Phase 4, Open Label, Non-comparative, Interventional, Multicenter Study to Evaluate the Safety of Dostarlimab in Adult Patients in India With Mismatch Repair Deficient (dMMR)/Microsatellite Instability-high (MSI-H) Recurrent or Advanced Endometrial Cancer (EC) That Has Progressed on or Following Prior Treatment With a Platinum-containing Regimen

The goal of this study is to evaluate the safety profile of dostarlimab in Indian adults with recurrent or advanced endometrial cancer.

开始日期2025-04-17

申办/合作机构

GSK Plc

NCT06405230

/ Not yet recruiting临床1/2期

A Pilot/Exploratory Translational Study to Evaluate Response to Dostarlimab and Pembrolizumab in Patient-derived Organoids and by Zirconium-89 Labelled Programmed Death Ligand 1 Positron Emission Tomography in Participants With Recurrent Non-small Cell Lung Cancer

The goal of this clinical trial is to investigate the utility of two biomarker tools: Patient-derived organoid (PDOs) and PDL1 PET imaging for predicting how participants with recurrent NSCLC respond to standard of care treatment in the advanced/metastatic stages.

开始日期2025-03-31

申办/合作机构

GSK Plc

100 项与多塔利单抗相关的临床结果

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100 项与多塔利单抗相关的转化医学

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100 项与多塔利单抗相关的专利（医药）

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166

项与多塔利单抗相关的文献（医药）

2025-07-01·Clinical and Translational Radiation Oncology

Rectal stenosis after immunotherapy in a mismatch repair deficient rectal cancer. Case report and review of literature

Article

作者: Bachmann, Robert ; Schempf, Ulrike ; Schroeder, Christopher ; Bitzer, Michael ; Steinle, Marc ; Hoffmann, Rüdiger ; Niyazi, Maximilian ; Mattern, Sven ; Büttner, Marcel ; Gani, Cihan ; Singer, Stephan

We report the case of a 57-year-old male patient who presented with a circumferential cT3 cN1 rectal adenocarcinoma in the mid rectum. The tumor was found to be mismatch repair deficient/microsatellite instable (dMMR/MSI). Instead of multimodality treatment with chemoradiotherapy immunotherapy with Dostarlimab was initiated. Treatment was well-tolerated in general and endoscopy and MRI showed early signs of treatment response. Despite this, the patient developed intestinal obstruction due to scarring that required repeat balloon dilations. In contrast to other oncological treatments, obstructions may worsen during immunotherapy in dMMR rectal cancers. This information has to be considered when patients are consulted regarding the optimal treatment after disease.

2025-07-01·INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER

An ambispective, real-world multi-center study of DOstarlimab in patients with Recurrent or Advanced DNA mismatch repair deficient/microsatellite instability-high endometrial cancer (GEICO 120-R/DORA study)

Article

作者: García-Illescas, David ; Carbó, Anna ; Manzano, Aránzazu ; Ortega, María Eugenia ; Albertí, Facundo ; Masvidal, María ; Murata, Paola ; Cueva, Juan F ; Churruca, Cristina ; Palacio, Isabel ; Hernando, Blanca ; Estévez-García, Purificación ; Madariaga, Ainhoa ; Gost, Ester ; Mendiola, Marta ; Martín-Lorente, Cristina ; Redondo, Andrés ; Gallego, Alejandro ; Lozano, Inmaculada ; Gálvez, Fernando

OBJECTIVE:

Patients with advanced or recurrent endometrial cancer who experience progression following platinum-based chemotherapy have limited treatment options. The phase I GARNET trial showed the high efficacy of dostarlimab in treating mismatch repair deficient (dMMR) and/or microsatellite instability-high (MSI-H) endometrial cancer.

METHODS:

DORA is a multi-center, ambispective, observational real-world study evaluating the efficacy and safety of dostarlimab. The study included patients with dMMR/MSI-H endometrial cancer who had experienced tumor progression on or after a platinum-based treatment and had received at least 1 cycle of dostarlimab within the Spanish Expanded Access Program. The primary endpoints were objective response rate and duration of response.

RESULTS:

A total of 129 patients from 57 of the Spanish Research Group for Gynaecological Cancer (GEICO) affiliated hospitals were enrolled, with 125 evaluable for radiological response. The median duration of dostarlimab administration was 8.8 months (interquartile range; 13.2), and 73 patients (57%) remained on therapy at the data cutoff. With a median follow-up of 11.6 months (range; 0.8-30.1), the objective response rate was 53.6% (95% CI 44.4 to 62.5). Complete response was observed in 27 patients (21.6%), and partial response in 40 (32%), with a median time to response of 2.9 months (95% CI 2.6 to 3.6). The median duration of response was not reached. The probability of maintaining the response at 12 and 24 months was 84.98% (95% CI 70.8 to 92.5) and 73.39% (95% CI 50.5 to 86.9), respectively. Treatment was discontinued due to toxicity in 4.7% of patients.

CONCLUSIONS:

Dostarlimab monotherapy in dMMR/MSI-H endometrial cancer patients shows similar efficacy in real-world practice to that observed in the GARNET trial.

2025-06-01·Clinical Colorectal Cancer

A Phase Two, Single-Arm, Open-Label Study With Dostarlimab Monotherapy in Participants With Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer (AZUR-1)

Article

作者: Cercek, Andrea ; Szijgyarto, Zsolt ; Heinemann, Volker ; Bachet, Jean-Baptiste ; Capdevila, Jaume ; O'Donnell, Sean ; Salvatore, Lisa ; Starling, Naureen ; Chen, Eric ; Harfst, Lauren ; Bando, Hideaki

BACKGROUND:

Colorectal cancer (CRC) had the second highest cancer mortality worldwide in 2020; nearly a third of CRCs were rectal cancers (RC). A recent study demonstrated that dostarlimab, an immune-checkpoint inhibitor, was highly effective in treating mismatch repair deficient (dMMR) locally advanced RC as all included patients had a clinical complete response (cCR) without radiation or chemotherapy. This study's objective is to evaluate the efficacy and safety of dostarlimab monotherapy in patients with previously untreated locally advanced dMMR RC.

PATIENTS/METHODS:

AZUR-1 (NCT05723562) is a multicenter, open-label, nonrandomized, single-arm phase 2 study enrolling approximately 150 patients across 10 countries. Key eligibility criteria include dMMR status or microsatellite instability-high (MSI-H) phenotype. Dostarlimab 500 mg will be administered intravenously every 3 weeks for 9 cycles. The primary endpoint is cCR by independent central review (ICR) at 12 months. Key secondary endpoints include cCR by ICR at 24 and 36 months, and 3-year event-free survival by investigator assessment. Additional secondary endpoints include organ preservation rate at 3 years and disease-specific survival and overall survival at 5 years. Efficacy and safety will be assessed in all patients who receive ≥1 dose of dostarlimab. All patients will be followed for 5 years (unless consent is withdrawn).

CONCLUSIONS:

AZUR-1 will evaluate the efficacy of dostarlimab immunotherapy in dMMR/MSI-H RC. Utilizing novel aspects including long follow-up of all patients and standardization of clinical response assessment, this study will provide international multicentric data to evaluate tumor response in an immunotherapy setting and new evidence on long-term outcomes.

454

项与多塔利单抗相关的新闻（医药）

2025-05-26

·抗体圈

“黄金靶点”再添败绩，这个潜力方向或可期待？

在K药的带领下，PD-1成为抗肿瘤市场主流。同时，随着PD-1市场陷入红海竞争，药企正在急切寻找“下一个PD-1”。而与该靶点有诸多相似之处的TIGIT引起业界关注，曾一度成为巨头药企们争相布局的“黄金靶点”。TIGIT全称为T细胞免疫球蛋白和ITIM结构域蛋白，属于PVR（脊髓灰质炎病毒受体）样蛋白家族，是一种主要在T细胞和NK细胞表面表达的免疫检查点蛋白。TIGIT或通过与配体CD155结合，间接阻碍T细胞功能；或通过阻碍免疫细胞表面的共刺激受体CD266的激活，从而抑制免疫细胞活性。理论上，通过TIGIT抗体既能解除T细胞的抑制，又能解除NK细胞的抑制，达到加倍解除免疫抑制的功能。但是，就是这样被寄予厚望的“黄金靶点”，在现实中却并未如业界期望的那般顺利。近日， GSK宣布，将终止与iTeos Therapeutics 合作研发的TIGIT单抗EOS-448（belrestotug）项目。至此，TIGIT靶点的坟场再多一具英雄骨。那么，TIGIT靶点还有破局可能吗？ 01 超6亿美元打水漂，EOS-448高开低走2021年，GSK与 iTeos Therapeutics 达成协议，双方将共同开发和商业化后者的EOS-448，这是一种具有 Fc 活性的人类免疫球蛋白 G1 (IgG1)单克隆抗体，通过与TIGIT（ T 细胞免疫球蛋白和免疫受体酪氨酸抑制基序结构域）和FcγR（免疫反应的关键调节因子）结合的多方面免疫调节机制，来增强抗肿瘤反应。根据协议条款，iTeos Therapeutics将收到6.25亿美元的预付款，以及最高 14.5亿美元的开发和商业里程碑付款。GSK由此切入TIGIT赛道。在研发初期，EOS-448一直很顺利。2024年5月，在iTeos Therapeutics发布的用于一线治疗 PD-L1 高表达NSCLC的II期临床研究GALAXIES Lung-201中，EOS-448超出了预设疗效标准，并具有临床意义的肿瘤缩小。试验结果显示，所有剂量的EOS-448+dostarlimab组合疗法与dostarlimab（抗PD-1单抗）单药治疗相比，显著改善了患者的客观缓解率（ORR）。组合疗法组的确认ORR约为60%，而单药组的确认ORR为28.1%。基于此，公司CEO甚至公开宣称，“我们的TIGIT是最为与众不同的”。但是在最新的公告中，iTeos表示EOS-448的两项临床研究结果均没有达到继续开发的既定疗效标准。在一项关键II期临床研究中，评估了EOS-448与GSK的PD-1抑制剂Jemperli联合用于未经治疗、局部晚期或转移性PD-L1高表达NSCLC患者。虽然该联合疗法在主要终点ORR方面有所改善，但无进展生存期（PFS）的结果却未达到具有临床意义的水平。而在另外一项针对PD-L1阳性头颈鳞状细胞癌的II期临床试验中，通过对中期分析发现，EOS-448与Jemperli联用，与Jemperli单药治疗组相比，反应率趋势低于有意义的阈值。基于以上研究结果，GSK和iTeos决定终止EOS-448项目及其合作，至此，所有包含EOS-448的试验都将终止。GSK的6.25亿美元首付款打了水漂。 02 挫折频现，TIGIT迎来至暗时刻TIGIT作为继PD-1/PD-L1之后的新一代免疫检查点，其能够通过与CD155等配体结合，调控T细胞和NK细胞的活性。这种“双重免疫激活”的理论模型，让TIGIT迅速成为肿瘤免疫领域的焦点。一众MNC早已下场入局，但大部分吃了败仗。首先是TIGIT靶点发现者——罗氏，也是TIGIT赛道的领军者。其旗下Tiragolumab 是一款靶向TIGIT的单抗，2016年开始启动临床试验。当时行业预测TIGIT药物市场规模将在2030年突破50亿美元。然而后续的研究进展并不顺利，Tiragolumab 在广泛期小细胞肺癌（ES-SCLC）和NSCLC两大适应症上连续失利，成为全球首个TIGIT III期临床失败案例。在 24 年财报中，罗氏放弃了Tiragolumab 的多项临床研究： 2 项 III 期临床、2 项 II 期临床、1 项 I 期联合治疗临床试验。2025 年 Q1 财报中，Tiragolumab 联合PD-L1单抗Tecentriq（阿替利珠单抗）治疗局部晚期食管癌的 III 期研究也被移除。诺华曾在2021年以3亿美元首付款引进百济神州的抗TIGIT疗法Ociperlimab（欧司珀利单抗，BGB-A1217），作为肺癌潜在治疗方法。但是2023年7月，由于“风险收益比不理想”，便将权益退还给了百济神州。在与诺华终止合作后，百济神州曾独立推进该项目，但最终仍未能突破肺癌疗效瓶颈。今年4月，百济神州宣布，将不再继续投资Ociperlimab的研发。而截至2024年上半年，百济神州已在Ociperlimab项目累计投入20.9亿元。同样在2021年，BMS通过和Agenus公司合作，获得Agenus专有双特异性抗体项目AGEN1777 的全球独家许可。Agenus将获得2亿美元的预付款和高达13.6亿美元的开发、监管和商业里程碑等。AGEN1777 是一种潜在FIC双特异性抗 TIGIT 抗体，采用增强的 Fc 区进行设计，具有高结合亲和力并可提高 T 细胞和 NK 细胞活化能力。在临床前研究中，这种方法在单独使用抗PD-1或抗 TIGIT单特异性抗体无效的肿瘤模型中显示出巨大的潜力。但是在后续研发中，AGEN1777 并未达到预期。2024年，BMS终止与Agenus的合作，将AGEN1777“退货”。此外，2023年，默沙东宣布其PD-1+TIGIT 复方制剂MK-7684A二线治疗转移性NSCLC的II期KeyVibe-002研究未达预期。2024年5月，默沙东宣布暂停其TIGIT疗法——Vibostolimab和K药联合用于可手术高危黑色素瘤辅助治疗的III期临床研究KeyVibe-010，原因是免疫副作用导致的脱落率太高。2024年8月，默沙东再次终止了Vibostolimab联用K药用于一线治疗SCLC 的III期临床；2024年12月，默沙东正式宣告终止Vibostolimab的临床开发项目。至此，TIGIT作为曾经被寄予厚望的肿瘤免疫治疗靶点，如今已进入至暗时刻。不过，也可能是黎明前的黑暗。目前，仍有药企坚持在TIGIT赛道。 03 双抗会成为突围方向吗？尽管在TIGIT的坟场，尸骨累累，但仍有一些孤勇者在这条赛道上继续深耕。在TIGIT下半场，这些药企或将双抗、或将药物联用作为主要突破口。其中多家企业放弃TIGIT单抗，直接从PD-1/TIGIT双抗切入。进展最快的当属阿斯利康，其PD-1/TIGIT双抗Rilvegostomig目前正在开展联合贝伐珠单抗 ±Tremelimumab （抗CTLA-4单抗）一线治疗肝细胞癌（HCC）的 III 期研究。这是该药首次针对 HCC 启动的 III 期临床研究。在国内，阿斯利康还开展了在PD-L1 TPS ≥50%的一线NSCLC患者中头对头对比K药的III期研究ARTEMIDE-Lung04。礼来和信达合作，共同开发了PD-1/TIGIT双抗IBI321曾在2021年启动1期临床试验，暂无更多公开信息公布。国内泽璟生物则开发了PD-1/TIGIT双抗ZG005。2024年，泽璟生物公布了ZG005针对晚期实体瘤患者的I/II期研究结果：ZG005呈现出良好的耐受性和安全性。特别是在接受20 mg/kg剂量治疗的晚期宫颈癌患者中初步结果显示疗效更优，ORR达到63%。目前，ZG005还在开展针对肝癌、神经内分泌瘤、NSCLC等的I/II期研究。另外，罗氏虽然屡战屡败，但其管线中仍有TIGIT的位置。目前，tiragolumab联合Tecentriq用于一线治疗不可切除III期NSCLC，以及联合Tecentriq和贝伐珠单抗用于一线治疗HCC的临床研究，都在进行中。诚然，针对TIGIT的药物研发基本以失败告终，短短几年间，这一靶点便由资本热捧变为弃子，但业界并未完全放弃这一靶点，双抗是否是未来的突围方向，目前仍存在诸多疑问。但几乎任何一个靶点的药物研发都不是一帆风顺的，PD-1(L1)也不例外。何况，TIGIT直到2009年才被罗氏旗下基因泰克发现，仍是一个年轻的靶点，未来变数很大。参考：GSK, iTeos pull the plug on belrestotug as TIGIT stumbles again；firstworld.https://www.biospace.com/business/beigene-scraps-tigit-candidate-after-underwhelming-lung-cancer-data.Innovent Announces the First Patient Dosed in the Phase 1 Study of IBI321 (Anti-PD-1/TIGIT Bispecific Antibody) in Patients with Advanced Malignant Tumors. https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c.识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！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。

引进/卖出临床2期免疫疗法

2025-05-19

·BioSpace

Deep Dive: Checkpoint Inhibitors at a Crossroads

A new generation of checkpoint inhibitors is emerging, with some showing more promise than others. From recent TIGIT failures to high-potential targets like VEGF, BioSpace explores what’s on the horizon in immuno-oncology. Eleven years after Merck’s Keytruda transformed the treatment space for several cancers, immuno-oncology—and checkpoint inhibitors (CPI) especially—are, optimistically speaking, at a crossroads. For those who see the glass as half empty, on the other hand, the space is frustratingly stalled. “The first wave of immuno-oncology has passed us by,” Jeremy Levin, CEO of Ovid Therapeutics, told BioSpace in March. As of April 2025, the FDA had approved 14 checkpoint inhibitors, but response rates to this type of immunotherapy have plateaued at around 30% , leaving 70% of patients out in the cold. Once highly touted checkpoints, such as TIGIT, have largely failed, while CTLA-4 hasn’t yielded nearly the number of therapies as PD-1/PD-L1. There is hope, however. Bristol Myers Squibb broke through in March 2022 with the FDA approval of relatlimab (marketed in combination with Opdivo as Opdualag ), the first LAG-3-blocking antibody, and today, much of the excitement centers on ivonescimab, a PD-1/VEGF bispecific antibody being developed by Summit Therapeutics. With the overall immuno-oncology market projected to reach some $284 billion by 2033 , these companies and more are actively vying for a piece of the pie. DATA SOURCE: MERCK EARNINGS , BIOPHARMA DIVE TIGIT Trouble Companies targeting TIGIT have been riding a rollercoaster the past five years. Roche spurred excitement for this novel checkpoint in December 2021 with promising Phase II results from its anti-TIGIT tiragolumab in combination with its anti-PD-L1 Tecentriq in metastatic non-small cell lung cancer (NSCLC). It was not to last, however, as last year the combo failed to significantly improve progression-free and overall survival versus Keytruda and chemotherapy in NSCLC in a Phase II/III study. This followed similarly disappointing news from Merck, whose anti-TIGIT antibody vibostolimab, when paired with Keytruda, also failed in a Phase II NSCLC trial. The field was somewhat revived last September when iTeos Therapeutics’ anti-TIGIT belrestotug, in combination with GSK’s anti-PD-1 therapy Jemperli, bested Jemperli monotherapy in terms of confirmed objective response rate by 30% in NSCLC. Other players in this space include BeiGene, AstraZeneca, Gilead and Arcus Biosciences. VEGF in the Spotlight Many industry observers extol the value of combination therapies in immuno-oncology. One such combo generating particular attention is a PD-1/VEGF bispecific antibody being developed by Summit Therapeutics. Last September, Summit set the cancer space ablaze when it announced that ivonescimab beat Keytruda in a Phase III trial in advanced NSCLC. Ivonescimab “is really the new . . . wave of checkpoint inhibitors,” Christiana “Chris” Bardon, co-managing partner of MPM BioImpact, told BioSpace in March. Analysts cautioned, however, that the “results may or may not be generalizable beyond the China-focused patient population,” where the trial was conducted. Summit is currently running another Phase III trial in NSCLC in the U.S., with an expected primary completion date of April 2028, according to ClinicalTrials.gov . BioNTech is also a contender in this space, gaining full rights to PD-L1/VEGF-A bispecific antibody BNT327/PM8002 in the November 2024 acquisition of partner Biotheus. How will AI further the development of novel checkpoint inhibitors? Editor’s note: This article was originally published as a special edition of ClinicaSpace, BioSpace’ s weekly newsletter covering clinical trial results and research news, on April 21. You can subscribe here .

免疫疗法临床2期临床3期上市批准并购

2025-05-16

·VIP说

卵巢癌免疫治疗的历史性突破：默沙东宣布帕博利珠单抗为铂耐药卵巢癌带来PFS和OS的双重阳性获益

从今天起，请不要再说卵巢癌是免疫冷肿瘤，请不要再说卵巢癌对免疫治疗不敏感。某试验失败，只代表这个试验失败；不能代表所有的免疫治疗都会失败。今天，默沙东宣布：Keynote-B96取得阳性结果。图1.默沙东官网信息Keynote-B96是一项随机、双盲的III期临床试验，研究对象是铂耐药复发性卵巢癌（643例），随机分为两组：对照组：安慰剂+紫杉醇±贝伐珠单抗试验组：帕博利珠单抗+紫杉醇±贝伐珠单抗主要终点是PFS，OS是次要终点。请注意：试验组和对照组的唯一区别在于是否使用帕博利珠单抗，没有其他别的混杂因素。图2.Keynote-B96研究根据默沙东的信息：与对照组相比，加用帕博利珠单抗后显著提高了PD-L1阳性人群和全人群的PFS；尤为关键的是，PD-L1阳性人群的OS也得到显著改善！这是卵巢癌历史上第一个单独加用免疫治疗后取得OS阳性结果的研究！图3.默沙东官网信息回顾卵巢癌免疫治疗的探索历程，一个客观事实是：既往卵巢癌免疫治疗失败的III期研究，用的免疫检查点抑制剂全部都是PD-L1单抗，包括阿替利珠单抗的ATALANTE研究、ENGOT-Ov41研究和IMagyn050研究，阿维鲁单抗的JAVELIN Ovarian 200研究、 JAVELIN Ovarian 100研究和JAVELIN OVARIAN PARP 100研究，等等，全部都是PD-L1单抗。而回顾PD-1单抗在卵巢癌中的探索，不得不再提一下多塔利单抗。去年12月20日，GSK宣布：对于晚期一线的卵巢癌患者，与化疗（±贝伐珠单抗）+尼拉帕利相比，再加上多塔利单抗之后，主要终点PFS取得显著获益。图4.GSK官网信息这个研究也非常关键，因为这个研究中的试验组和对照组都加上PARP抑制剂，两组的唯一区别也是在于用或不用免疫治疗，没有任何别的影响因素。这个研究的具体数据结果将在下个月的ASCO年会上公布。尽管在此之前，卵巢癌已有两个III期研究取得阳性结果，但是因为存在混杂因素，所以大家始终怀疑免疫究竟能不能为卵巢癌带来获益。DUO-O研究是第一个取得阳性结果的研究，但存在争议：与化疗+贝伐相比，化疗+贝伐+度伐利尤单抗+奥拉帕利取得PFS显著获益，但化疗+贝伐+度伐利尤单抗没有获益；所以就不知道前者的获益是不是由奥拉帕利引起的，尽管本试验纳入的是非BRCA突变的患者。图5.DUO-O试验Keylynk-00研究是第二个取得阳性结果的研究，但其设计和DUO-O相似，结果也和DUO-O相似，所以同样存在争议：与化疗±贝伐相比，化疗±贝伐+帕博利珠单抗+奥拉帕利取得PFS显著获益，但是化疗±贝伐+帕博利珠单抗没有获益。图6.Keylynk-00研究如今，包括多塔利单抗、包括帕博利珠单抗的Keynote-B96研究，试验组与对照组的唯一影响因素就是免疫检查点抑制剂，彻底摆脱争议。去年GSK宣布多塔利单抗的这个研究结果的时候，大家仍然不看好卵巢癌的免疫治疗，因为这个研究中只有PFS（主要终点）取得阳性结果，作为次要终点的OS没有获益。现在Keynote-B96研究取得PFS和OS的双重阳性结果，我想应该没有任何争议了。目前，默沙东只是宣布了Keynote-B96研究取得阳性结果的结论，具体的数据还未公布，估计要等到下半年的ESMO年会，或者明年年初的SGO年会才会公布。那么，回顾卵巢癌免疫治疗的探索之路，发现其实我们是在一步一步地进步、一步一步地上升。从最开始PD-L1单抗的失败，到后面免疫联合PARP抑制剂取得阳性结果（尽管有争议），再到后来的多塔利单抗取得PFS获益（尽管OS没有获益），再到今天帕博利珠单抗取得PFS和OS的双重阳性结果。所以，还是那句话：只要我们不放弃，只要我们保持信心，结局总会越来越好。最后，总结：从今天起，请不要再说卵巢癌是免疫冷肿瘤，请不要再说卵巢癌对免疫治疗不敏感。某试验失败，只代表这个试验失败；不能代表所有的免疫治疗都会失败。

ASCO会议临床结果临床3期免疫疗法

100 项与多塔利单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	多塔利单抗	L01XC	DB15627

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
晚期子宫内膜癌	欧盟	GlaxoSmithKline (Ireland) Ltd.	2024-01-12
晚期子宫内膜癌	冰岛	GlaxoSmithKline (Ireland) Ltd.	2024-01-12
晚期子宫内膜癌	列支敦士登	GlaxoSmithKline (Ireland) Ltd.	2024-01-12
晚期子宫内膜癌	挪威	GlaxoSmithKline (Ireland) Ltd.	2024-01-12
复发性子宫内膜癌	欧盟	GlaxoSmithKline (Ireland) Ltd.	2024-01-12
复发性子宫内膜癌	冰岛	GlaxoSmithKline (Ireland) Ltd.	2024-01-12
复发性子宫内膜癌	列支敦士登	GlaxoSmithKline (Ireland) Ltd.	2024-01-12
复发性子宫内膜癌	挪威	GlaxoSmithKline (Ireland) Ltd.	2024-01-12
MMRD实体瘤	美国	GlaxoSmithKline LLC	2021-08-17
MSI-H 子宫内膜癌	欧盟	GlaxoSmithKline (Ireland) Ltd.	2021-04-21
MSI-H 子宫内膜癌	冰岛	GlaxoSmithKline (Ireland) Ltd.	2021-04-21
MSI-H 子宫内膜癌	列支敦士登	GlaxoSmithKline (Ireland) Ltd.	2021-04-21
MSI-H 子宫内膜癌	挪威	GlaxoSmithKline (Ireland) Ltd.	2021-04-21
错配修复缺陷子宫内膜癌	欧盟	GlaxoSmithKline (Ireland) Ltd.	2021-04-21
错配修复缺陷子宫内膜癌	冰岛	GlaxoSmithKline (Ireland) Ltd.	2021-04-21
错配修复缺陷子宫内膜癌	列支敦士登	GlaxoSmithKline (Ireland) Ltd.	2021-04-21
错配修复缺陷子宫内膜癌	挪威	GlaxoSmithKline (Ireland) Ltd.	2021-04-21

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
PD-L1阳性非小细胞肺癌	临床3期	美国	GSK Plc	2024-06-10
PD-L1阳性非小细胞肺癌	临床3期	中国	GSK Plc	2024-06-10
PD-L1阳性非小细胞肺癌	临床3期	日本	GSK Plc	2024-06-10
PD-L1阳性非小细胞肺癌	临床3期	阿根廷	GSK Plc	2024-06-10
PD-L1阳性非小细胞肺癌	临床3期	比利时	GSK Plc	2024-06-10
PD-L1阳性非小细胞肺癌	临床3期	巴西	GSK Plc	2024-06-10
PD-L1阳性非小细胞肺癌	临床3期	保加利亚	GSK Plc	2024-06-10
PD-L1阳性非小细胞肺癌	临床3期	加拿大	GSK Plc	2024-06-10
PD-L1阳性非小细胞肺癌	临床3期	芬兰	GSK Plc	2024-06-10
PD-L1阳性非小细胞肺癌	临床3期	法国	GSK Plc	2024-06-10

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临床结果

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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


NCT04165772 (NEWS \| Pubmed) 人工标引	临床2期	MSI-H 癌症 \| 错配修复缺陷直肠癌新辅助 Deficient DNA Mismatch Repair (dMMR)	117	Dostarlimab	醖襯鑰醖鏇積鹽窪廠鑰(衊衊襯淵繭選積選簾鬱) = 積淵衊範鏇蓋範鑰廠廠觸簾膚築構窪蓋構網窪 (餘遞鏇鏇壓積鬱廠壓鹹 ) 更多	积极	2025-04-27
				Dostarlimab (dMMR, locally advanced rectal cancer)	鑰齋襯鑰鬱餘顧獵衊艱(廠艱觸繭願簾鏇願壓範) = 範鏇襯膚範顧餘蓋鏇廠齋選獵製繭範夢襯淵糧 (齋糧膚襯顧簾壓糧鬱夢 ) 更多
NCT04581824 (PERLA, ESMO_ELCC2025)	临床2期	转移性非鳞状非小细胞肺癌一线 PD-L1 status	-	Dostarlimab plus chemotherapy	壓鹽遞遞糧繭壓獵構壓(製繭鬱醖製積鏇範鏇簾) = 積構糧鬱築齋觸糧夢膚憲醖觸鏇衊範憲顧網膚 (簾壓窪網餘襯製壓淵衊, 14.5 ~ 27.3) 更多	积极	2025-03-26
				Pembrolizumab plus chemotherapy	壓鹽遞遞糧繭壓獵構壓(製繭鬱醖製積鏇範鏇簾) = 鏇鹽觸構襯壓醖遞窪糧憲醖觸鏇衊範憲顧網膚 (簾壓窪網餘襯製壓淵衊, 11.6 ~ 19.3) 更多
NCT06655818 (CTgov)	临床1/2期	多发性骨髓瘤	4	Mafodotin+Dostarlimab+Belantamab	繭鹽壓範憲鹽鑰憲襯餘 = 窪淵淵膚餘網願積鑰築廠鑰顧廠鬱艱簾壓願選 (繭淵網積壓憲廠鹽襯積, 願憲膚窪餘鑰網糧衊膚 ~ 鑰鏇餘壓膚簾遞鬱構築) 更多	-	2025-03-03
NCT03602859 (FIRST-ENGOT-OV44, PipelineReview) 人工标引	临床3期	卵巢癌一线	-	SOC + Placebo	糧鬱構憲鑰網製夢積簾(蓋範鑰顧廠餘遞鬱鹹襯) = The trial met its primary endpoint of PFS demonstrating a statistically significant difference with the addition of dostarlimab to both standard of care carboplatin-paclitaxel chemotherapy and niraparib maintenance, with or without bevacizumab. 鹹壓繭艱夢齋觸夢範憲 (襯憲鏇壓糧壓遞繭獵構 ) 达到更多	积极	2024-12-20
				SOC + niraparib
NCT05723562 (AZUR-1, Company_Website) 人工标引	临床2期	错配修复缺陷直肠癌一线 MSI-High \| Deficient DNA Mismatch Repair (dMMR)	42	dostarlimab	憲遞構壓憲遞鏇鏇願鑰(糧觸繭築觸製蓋網獵構) = 積衊艱簾鬱鏇夢遞憲艱簾衊鹽獵觸遞鏇衊壓齋 (淵窪築遞窪觸網觸築觸 )	积极	2024-12-16
Korean expanded access program (ESMO_ASIA2024)	N/A	复发性子宫内膜癌 dMMR \| MSI-H	29	Dostarlimab 500mg	獵選構憲齋憲衊簾齋鏇(繭膚選襯襯鏇廠築繭壓) = Serious AEs occurred in 4 (13.8%) pts; none were directly related to treatment 網觸範積築淵衊壓築鏇 (鹽醖範襯築齋膚製積構 ) 更多	积极	2024-12-07
NCT04581824 (PERLA, SITC2024) 人工标引	临床2期	非鳞状非小细胞肺癌	243	Dostarlimab + CT	齋鹹鹽築觸鏇選鹹鹹鹽(廠膚鏇積衊顧艱壓衊鹽) = 繭製夢廠襯襯顧鏇鹽齋鑰鬱衊鹽膚積積積糧製 (鑰糧築繭衊網艱醖選蓋, 14.5 ~ 27.3)	积极	2024-11-05
				Pembrolizumab + CT	齋鹹鹽築觸鏇選鹹鹹鹽(廠膚鏇積衊顧艱壓衊鹽) = 積醖積築繭獵築鑰醖夢鑰鬱衊鹽膚積積積糧製 (鑰糧築繭衊網艱醖選蓋, 11.6 ~ 19.3)
NCT05565378 (GALAXIES Lung-201, GlobeNewswire) 人工标引	临床2期	PD-L1阳性非小细胞肺癌一线 PD-L1 High Expression	124	Dostarlimab	窪範壓製簾蓋鏇獵鬱鑰(繭淵顧鹹淵蓋襯膚簾夢) = 選構廠憲築構選選壓壓築製遞積齋鑰蓋醖蓋顧 (觸構積鹹鬱積顧蓋簾鹹, 21.1–56.3) 更多	积极	2024-09-14
				Dostarlimab + belrestotug 100 mg	窪範壓製簾蓋鏇獵鬱鑰(繭淵顧鹹淵蓋襯膚簾夢) = 鬱醖願積選餘鬱壓遞遞築製遞積齋鑰蓋醖蓋顧 (觸構積鹹鬱積顧蓋簾鹹, 43.9–80.1) 更多
NCT05565378 (GALAXIES Lung-201, ESMO2024) 人工标引	临床2期	PD-L1阳性非小细胞肺癌一线 PD-L1 High Expression (TPS >= 50%)	124	Dostarlimab 500 mg	積製鹽積鹹醖醖築夢顧(窪遞積廠願獵醖餘襯觸) = 遞製繭願糧糧觸簾鑰糧製艱醖積遞顧鏇夢鑰鏇 (繭壓願網憲選範製壓簾, 21.1 ~ 56.3) 更多	积极	2024-09-14
				Dostarlimab 500 mg + Belrestotug 100 mg	積製鹽積鹹醖醖築夢顧(窪遞積廠願獵醖餘襯觸) = 鬱鏇願艱選淵願蓋觸製製艱醖積遞顧鏇夢鑰鏇 (繭壓願網憲選範製壓簾, 43.9 ~ 80.1) 更多
NCT05065021 (Re-VOLVE, ESMO2024) 人工标引	临床2期	卵巢癌	20	Niraparibbevacizumabniraparibpaclitaxeldostarlimab	顧製醖醖蓋齋齋簾憲醖(選願壓艱構鬱餘齋餘觸) = 網蓋鑰選鑰襯獵簾醖鹹壓壓壓鏇選遞壓觸觸鹹 (鹽壓鹽鏇遞壓艱鹹鹹鹽 ) 更多	积极	2024-09-14