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+ [81]

非在研适应症

晚期胆道癌胆管癌透明细胞肉瘤+ [5]

原研机构

AnaptysBio, Inc.

在研机构

GSK PlcApices Soluciones SL

Tesaro, Inc.

+ [7]

非在研机构-

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

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结构/序列

Sequence Code 315609369H

来源: *****

Sequence Code 315609370L

来源: *****

关联

101

项与多塔利单抗相关的临床试验

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

NCT06879717

/ Not yet 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2025-04-01

申办/合作机构

iOnctura SA初创企业

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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159

项与多塔利单抗相关的文献（医药）

2025-04-01·INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER

Phase 2b, open-label, single-arm, multicenter pilot study of the efficacy, safety, and tolerability of dostarlimab in women with early-stage mismatch repair-deficient endometrioid endometrial adenocarcinoma

Article

作者: Mak, Blossom ; Kuchel, Anna ; Brand, Alison ; Gebski, Val ; McNally, Orla ; Mileshkin, Linda ; Jobling, Thomas ; Goh, Jeffrey ; Baxter, Eva ; Obermair, Andreas

BACKGROUND:

The standard treatment for endometrial cancer is hysterectomy with or without bilateral salpingo-oophorectomy; however, this may not be an optimal choice for women who have not completed childbearing or who are at a high risk of surgical complications. Conservative treatment with levonorgestrel intrauterine devices appear to be effective in patients with early-stage endometrial cancer; however, patients with mismatch repair-deficient (dMMR) tumors have a low likelihood of responding to levonorgestrel intrauterine devices.

PRIMARY OBJECTIVE:

To assess the efficacy of dostarlimab, an active immune checkpoint inhibitor that targets the programmed cell death protein-1 receptor, in patients with early-stage dMMR endometrioid endometrial adenocarcinoma.

STUDY HYPOTHESIS:

Administration of 4 3-weekly cycles of 500 mg dostarlimab followed by a 3-week rest period and 3 6-weekly cycles of 1000 mg dostarlimab will be safe and efficacious in early-stage dMMR endometrial cancer patients.

TRIAL DESIGN:

Non-randomized, open-label, pilot, multicenter phase2b study designed to evaluate the efficacy and safety of dostarlimab in 10 women aged ≥18 years with a clinically confirmed diagnosis of early-stage and dMMR endometrioid endometrial adenocarcinoma.

MAJOR INCLUSION/EXCLUSION CRITERIA:

Eligible patients must have histologically proven stage I, International Federation of Gynecology and Obstetrics grade 1 or 2 dMMR endometrioid endometrial adenocarcinoma and desire for fertility preservation. Exclusions include, but are not limited to, patients with other high-risk endometrial cancer cell types, a poor medical risk due to uncontrolled medical conditions, or those who experienced grade 3 or higher immune-related adverse events from prior immunotherapy.

PRIMARY ENDPOINT(S):

The primary endpoint is the number of participants achieving investigator-assessed pathological complete response within 6 months of treatment.

SAMPLE SIZE:

Ten (10) women ≥18 years of age will be enrolled.

ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS:

Accruals are expected to be completed by 2027, with the presentation of results by 2029.

TRIAL REGISTRATION:

NCT06278857.

2025-03-01·BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Population pharmacokinetics and exposure–response relationships of dostarlimab in primary advanced or recurrent endometrial cancer in part 1 of RUBY

Article

作者: Oaknin, Ana ; Segev, Yakir ; Zub, Oleksandr ; Koliadi, Anthoula ; Pothuri, Bhavana ; Zajic, Stefan ; Berton, Dominique ; Jørgensen, Trine Lembrecht ; Alskär, Oskar ; Gennigens, Christine ; Backes, Floor J. ; Melhem, Murad ; André, Thierry ; Krivak, Tom ; Bouberhan, Sara ; Shahin, Mark S. ; Pishchyk, Mikalai ; Buscema, Joseph ; Hanze, Eva ; Jain, Angela ; Kuchimanchi, Mita

Aims:

Dostarlimab‐gxly is a humanized monoclonal antibody of the IgG4 isotype that binds to the programmed cell death protein‐1 (PD‐1) receptor and blocks its ligands. RUBY (NCT03981796) is a two‐part multicentre study in patients with recurrent or primary advanced endometrial cancer. The overall aims were to characterise the population pharmacokinetics (PopPK) from Part 1 of this study, identify relevant covariates of interest, and assess exposure–efficacy/safety (ER) relationships.

Methods:

A PopPK model developed using GARNET (NCT02715284) study data for dostarlimab monotherapy was externally validated with RUBY Part 1 study data. Subsequently, the model was updated with data across the two studies. Exposure–safety analyses for adverse events related to dostarlimab alone or in combination with standard of care (SOC) were modelled using logistic regression. Exposure–efficacy analysis included Cox proportional hazards analysis of the primary efficacy endpoint of progression‐free survival (PFS).

Results:

For the model update, 7957 pharmacokinetics observations from 868 patients pooled from both RUBY and GARNET studies were available. The model was consistent with the previous model. Dostarlimab clearance was estimated to be 7.79% lower when dostarlimab was given as SOC combination therapy. However, no significant covariates were clinically relevant. Hepatic or renal impairment did not affect pharmacokinetics. Among the safety endpoints, only rash showed a small yet statistically significant effect (P < .05) in all subjects; however, this was not not deemed clinically relevant. There were no other clinically significant exposure–safety or exposure–PFS relationships.

Conclusions:

The addition of chemotherapy to dostarlimab had limited effect on dostarlimab PopPK, with no clinically significant covariates or clinically relevant exposure–safety or exposure–PFS relationships.

2025-02-01·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: Szijgyarto, Zsolt ; Cercek, Andrea ; Heinemann, Volker ; Bachet, Jean-Baptiste ; Capdevila, Jaume ; Salvatore, Lisa ; O'Donnell, Sean ; 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.

426

项与多塔利单抗相关的新闻（医药）

2025-04-09

·VIP说

肿瘤免疫治疗策略2.0

# 本篇笔记仅基于公开资料和信息撰写、为个人观点、供学术交流所用、不构成任何建议 #我用了差不多一个月的时间，看了几十家代表公司的产品线、几千篇研报和点评、几万个注册临床试验，想要看清楚肿瘤免疫治疗棋局的现状和未来。这不符合我的本性，我是宁可去无人区探险，也不想投入毫厘铢锱不能差错的极致内卷中。但是，现实就是，现在和未来很长一段时间内，免疫检查点抑制剂都会是肿瘤治疗的基石，即使MNC们早就已经布局于免疫检查点抑制剂之外甚至肿瘤治疗之外，国内大多数药企还有一段国产替代的长路要走。既然不能提前退休，只能强忍着非常严重的内卷PTSD看棋局，这种不适感压制了我的段子手级别语言天赋，所以这篇笔记会写的非常......直白。我个人给免疫治疗策略1.0的定义，就是大家手里都有个PD-(L)1抑制剂产品。全球已经有32个/国内已经有24个PD-(L)1抑制剂产品上市。图片引用来自“IO笔记”。至于免疫治疗策略2.0，就是如何进一步迭代和升级。PD-(L)1抑制剂产品本身的迭代和升级，目前大家的策略非常一致，改良单抗本身没能创造出什么奇迹，就开发双抗/多抗和复方，以及皮下注射、口服小分子、ADC等新剂型。双抗/多抗和复方本质类似于联合给药方案，所以放到后面再说。开发皮下注射剂型看上去是个捷径，不过如果大家的目标是国际市场，可能会有专利侵权风险：阿斯利康7.5亿美元引进Alteogen透明质酸酶技术，后者深陷侵权风险口服小分子PD-(L)1抑制剂，我是没有“小药说药”那么关注，而且似乎已经冷却：靶向PD-1/PD-L1小分子药物的研究进展至于PD-(L)1 ADC，反正已经热闹起来：靶向PD-L1 ADC：辉瑞首次国内申报临床！复宏汉霖、映恩生物“勇攀高峰”此外，国内外很多家药企已经想开了，不搞什么伪创新药，帕博利珠单抗核心专利将于2028年到期，直接开发生物类似药。国内外我已经数出来10个帕博利珠单抗类似药在做注册临床试验了，还有3个纳武利尤单抗生物类似药。更广谱的迭代和升级策略，就是以PD-(L)1抑制剂产品为基石，开发各种联合给药方案。汇总信息还是医药魔方做得最漂亮（反正我下载了PPT）：PD-1/PD-L1抑制剂中美获批及全球注册性临床试验15年动态趋势医药魔方PPT中部分内容截图：类似的汇总信息报告和点评很多，都能让大家一眼看清楚肿瘤免疫治疗棋局已经内卷到什么地步，看完不但没有思路，反而更加焦虑了。所以我们还是采用最简单高效的fast follow的老办法，看看几十家代表公司的肿瘤免疫治疗产品线，看看follow谁家的具体策略最适合自家。1. 默沙东/默克帕博利珠单抗(PD-1单抗)，长期被群殴和围攻的药王，王冠太重。在肿瘤领域，默沙东/默克不断探索和拓展其各种联合给药方案，并且积极布局复方和皮下等新剂型，双抗等新产品，以求夯实其在肿瘤领域的领先地位。复方主要是MK-1308A(PD-1+CTLA-4，Pembrolizumab+Quavonlimab)，MK-7684A(PD-1+TIGHT，Pembrolizumab+Vibostolimab)，MK-4280A(PD-1+LAG-3，Pembrolizumab+favezelimab)，2024年12月宣布终止开发后两个，目前只有MK-1308A还在推进。皮下剂型MK-3475A的III期临床试验刚官宣成功。近年来，默沙东/默克的肿瘤产品线重点已经布局于免疫检查点抑制剂之外，但免疫检查点抑制剂还是肿瘤治疗的基石，肿瘤领域且没有禁忌症，什么新产品都尝试联联看，就像吃什么菜都要配一碗白米饭。看帕博利珠单抗适应症布局是一项极其艰巨的工作，我差不多用了半个月时间，剩下几十个产品用了剩下的半个月时间。太多了。不仅因为默沙东/默克财大气粗，有把握的III期试验开几百个，没把握的I-II期试验和IIT开几千个，更因为帕博利珠单抗是基石中的基石，米饭中的白米饭，其他药企开发联合给药方案也是首选帕博利珠单抗。即使默沙东/默克没有布局，其他药企也会填空，所有瘤种所有适应症，完全没有空缺。最后得去翻默沙东/默克官网的PPT，才能找出他家真正的主线。如果布局图里出现了个别空缺，那也是某些III期临床试验失败导致的，绝不是没人尝试过填空。比如大家都吃过瓜的LEAP系列。但是有三个瘤种，即著名的冷肿瘤们，卵巢癌、胰腺癌、前列腺癌，所有药企都是屡战屡败+屡败屡战。先驱栽坑里那是代价，后来者再盲目跳坑，我可能忍不住嘲笑了，如果不是颠覆性作用机制的新药，建议不要再尝试将免疫治疗用于这几个瘤种。2. BMS纳武利尤单抗(PD-1单抗)，没能问鼎药王，所以在此基础上早早开发出皮下注射剂型，与伊匹木单抗(Ipilimumab, CTLA-4)联合方案，与Relatlimab(LAG-3单抗)联合方案，甚至开发了复方OPDUALAG(Nivolumab+Relatlimab)，均已成功获批多个适应症。也曾在TIGHT、IDO等靶点药物联合方案上栽过跟头，最新产品是复方BMS-986489(PD-1+fucosyl-GM1, Nivolumab+BMS-986012)。近年来，BMS的肿瘤产品线重点也已经布局于免疫检查点抑制剂之外。但免疫检查点抑制剂还是肿瘤治疗的基石，主动或被动开发联合方案也非常多。3. 罗氏阿替利珠单抗(PD-L1单抗)，其实已经算差异化开发了，靶点从PD-1换成了PD-L1。阿替利珠单抗是早早成功开发了皮下注射剂型。之后开发双抗时换回PD-1单抗，包括Tobemstomig(RO7247669, PD-1/LAG-3)，Lomvastomig(PD-1/TIM-3, RO7121661)。罗氏在肿瘤免疫治疗方面不算成功，主要是因为阿替利珠单抗与Tiragolumab(TIGHT单抗)的联合方案投入太大，受伤太深。但是深挖一下新技术平台，还能翻出来PD1-IL2v，PDL1 LNA等产品。值得注意的是，阿替利珠单抗用于三阴性乳腺癌非常波折，各种姿势的III期临床试验失败和撤回适应症，鉴于特瑞普利单抗在同一适应症里取得过成功，咱们不能说三阴性乳腺癌不适合免疫治疗，但PD-1单抗似乎比PD-L1单抗强一些。肾癌、尿路上皮癌、头颈癌、宫颈癌里也有类似情况，建议谨慎选择PD-L1单抗。4. 阿斯利康度伐利尤单抗(PD-L1单抗)，早期策略和BMS类似，开发皮下注射剂型，还有和替西木单抗(Tremelimumab, CTLA-4)的联合给药方案。后来者的好处就是可以避开先驱们栽过的坑，适应症开发都比较顺利。现在已经不做复方了，直接换双抗，Volrustomig(PD-1/CTLA-4)，Sabestomig(PD-1/TIM-3)，Rilvegostomig (PD-1/TIGHT)。发起IO+ADC潮流的应该就是他家，而且他家明显艺高人胆大，最偏爱Rilvegostomig (PD-1/TIGHT)，这是要死磕TIGHT靶点的节奏。5. 辉瑞、吉列德、再生元、GSK、Incyte、BIOCAD可以说，辉瑞几乎错了肿瘤免疫治疗浪潮。Avelumab(PD-L1单抗)开发顺位非常靠后，所以从超级冷门小适应症下手—皮肤默克尔细胞癌，弯道超车获批上市后，目前仅在膀胱癌领域取得成功（联合阿昔替尼用于肾癌一线是基于PFS成功附条件获批，但是OS失败，现在很尴尬；用于非小细胞肺癌、头颈癌和胃癌都是全面失败）。后来一度想悄悄开发PD-1单抗皮下注射剂型Sasanlimab（未获批上市），最终还是抢跑PF-08046054(PD-1 ADC)。后来者后来到辉瑞这个地步，如果还不愿赌服输，就得这么另辟蹊径。但是Sasanlimab有点过，首个适应症居然选择联合BCG用于非肌层浸润性膀胱癌，之前帕博利珠单抗和纳武利尤单抗都挑战失败的适应症，全球均未有免疫检查点抑制剂类产品获批。吉列德也是后来者，但是通过收购Arcus获得了赛帕利单抗(Zimberelimab，PD-1单抗)，果然顺产没有顺手快。在国内，赛帕利单抗用于经典型霍奇金淋巴瘤和晚期宫颈癌已获批上市。但是他家的联合给药方案，目前以Domvanalimab(TIGHT单抗)为主，又是一个死磕TIGHT靶点的。再生元不算后来者，Cemiplimab(PD-1单抗)虽然不算先驱，但是通过小适应症—皮肤鳞状细胞癌和皮肤基底细胞癌，早早弯道超车获批上市。他家毕竟是资深肿瘤免疫疗法biotech，联合给药方案非常多，目前以联合Fianlimab(LAG-3单抗)为主。GSK不算后来者也不算先驱，多塔利单抗(Dostarlimab，PD-1单抗) 通过小适应症—dMMR/MSI-H子宫内膜癌，早早弯道超车获批上市，之后仅专注于子宫内膜癌、结直肠癌和头颈癌，坚定的反内卷思维，深得我心。Incyte真不容易，当初为了卡瑞利珠单抗和恒瑞分分合合，最后终于拥有了自己的Retifanlimab(PD-1单抗)。跟辉瑞类似，因为Retifanlimab开发顺位非常靠后，所以从超级冷门小适应症下手—皮肤默克尔细胞癌，弯道超车获批上市。后来居然又被再鼎引入中国继续开发，反正各种不容易。再看Incyte产品线，始终专注于肿瘤免疫疗法，口服PD-L1，PD-1/LAG-3双抗、PD-1/TGF-βRII双抗均有布局。Prolgolimab(PD-1单抗)由俄罗斯药企BIOCAD开发，获得俄罗斯卫生部批准上市，用于治疗转移性黑色素瘤。在两国总理的共同见证下，由上药集团引进入国内共同开发，上药集团不愧是一流国企，非常正确。值得一提的是，Prolgolimab都这么正确了也没有躺平，继续开发复方BCD-217(Prolgolimab+Nurulimab，PD-1+CTLA-4)，还开发了帕博利珠单抗生物类似药。6. 其他外企艾博维：Budigalimab(PD-1单抗)Budigalimab绝对算后来者，我个人高度怀疑艾博维是为了联合其他自家真爱的新产品才被迫开发了基石。到现在最高开发阶段II期临床试验。强生：Cetrelimab(PD-1单抗)也不知道这个产品是不是和辉瑞的Sasanlimab高度类似，首个适应症居然也选择非肌层浸润性膀胱癌，但联合了自家TAR-200，我个人觉得就是为了陪衬TAR-200。2025年1月15日，强生宣布递交TAR-200的上市申请，用于治疗卡介苗（BCG）不应答的高危非肌肉侵袭性膀胱癌（HR-NMIBC）伴原位癌（CIS）患者。此次递交通过实时肿瘤审评（RTOR）项目，允许FDA在完全申请正式递交之前就开始审评以加快进度。 TAR-200为一种膀胱内局部给药的新型递送系统，采用一种双重小片设计，材质为硅聚合物半透小管，吉西他滨在膀胱持续缓慢释放。BI：Ezabenlimab(PD-1单抗)反正我个人高度怀疑BI是为了联合其他自家真爱的新产品才被迫开发了基石。到现在最高开发阶段II期临床试验。安进：Zeluvalimab(PD-1单抗)在安进最新的产品线信息里已经找不到Zeluvalimab了，但是找到了纳武利尤单抗生物类似药，预期2025年获批上市。放弃死磕开发顺位过于滞后的伪创新药，拥抱生物类似药，拥抱效率和利润，毕竟肿瘤免疫治疗也不是安进公司的主线，顶多用来联合其他自家真爱的新产品。Agenus：Botensilimab(PD-1单抗)Agenus还算比较重视Botensilimab，但主要是为了配合新一代产品—Balstilimab(CTLA-4单抗)，声称可以将冷肿瘤转化为热肿瘤。首个适应症选择联合Balstilimab用于non-MSI-H结直肠癌。坚定的反内卷思维，深得我心。BioNTech：BNT327(PD-L1/VEGF双抗)等收购普米斯生物等biotechs，跳过肿瘤免疫治疗1.0时代，直接飞跃至2.0时代潮头，拥有各种最热门双抗和ADC，又是顺产哪有顺手快的成功案例和典型代表。不过最新的消息是BNT311(PD-L1/4-1BB双抗)退回Genmab，这不是一个好消息，真正成功的双抗也不多。BioNTech的策略虽然有抄袭AZ，但非常清晰明确，值得学习。先分析免疫检查点抑制剂单药或既往的联合给药方案，在全球范围内获批过哪些适应症，还有哪些细分人群中有未被满足的临床需求，既往放弃开发或开发失败适应症的困难在哪里。再分析或补充自家产品线里的产品，是否有新颖的作用机制可能攻克之前的困难。最后设计BNT327的临床开发计划：第一步，联合化疗去攻克确定性高、能快速实现高市场价值的适应症；第二步，联合各种新颖作用机制的新产品，填补之前未被满足的临床需求；第三步，探索更多、更新的联合给药方案和适应症。篇幅原因，写完外企部分已经快5000字了，改天再写国内企业部分。信息量过大，CPU干烧到头晕，所有重点点到即止，如有疏漏错误，请大家多包涵。# 本篇笔记仅基于公开资料和信息撰写、为个人观点、供学术交流所用、不构成任何建议 #

抗体药物偶联物免疫疗法生物类似药

2025-04-03

·Endpoints

Another TIGIT trial fails as BeiGene scraps Phase 3 drug

What was once a promising area of cancer immunotherapy has had another late-stage failure. BeiGene said Thursday that a Phase 3 study for its anti-TIGIT drug, called ociperlimab, was halted for futility after a recommendation from the trial’s independent data monitoring committee. The study’s primary endpoint was overall survival in patients with certain forms of metastatic non-small cell lung cancer. BeiGene has now elected to terminate development of ociperlimab. Researchers were testing a combination of BeiGene’s PD-1 inhibitor Tevimbra with ociperlimab against Merck’s Keytruda. A third study arm also administered Tevimbra as an active comparator. There were no new safety signals, BeiGene said in a release. The failure is the latest in a long-running list of recent TIGIT flops. Last year, Roche and Merck reported late-stage misses for their TIGIT programs, and Merck announced in December that it was discontinuing its drug. Bristol Myers Squibb returned the rights of a partnered TIGIT program to Agenus last year, and Gilead reworked a deal with Arcus to leave TIGIT out of their collaboration. Additionally, ociperlimab’s miss wasn’t the first time it ran into headwinds. Back in 2023, Novartis backed out of a partnership with BeiGene for the program. There is still some hope for the field. GSK and iTeos said in September that an anti-TIGIT drug combined with the PD-1 inhibitor Jemperli improved overall response rates in an advanced form of lung cancer. But the buzz is considerably smaller than a few years ago, when money was flowing toward research into these drugs.

临床3期免疫疗法临床失败

2025-03-28

·GlobeNewswire-Health Care

LIXTE Biotechnology Provides Update On Progress with Proprietary Compound, LB-100, to Treat Ovarian and Colorectal Cancer

-Started Two New Clinical Trials, Collaborating with MD Anderson and The Netherlands Cancer Institute for Treatment of Ovarian and Colorectal Cancer- -Received Exclusive Patent License Agreement with the NIH on LB-100's Potential in Enhancing Cancer Immunotherapies- -Two Breakthrough Publications in Medical Journals, EMBO and Cancer Discovery, Supporting LIXTE’s Clinical Trial Program- March 27, 2025 -- LIXTE Biotechnology Holdings, Inc. (“LIXTE” or the “Company”) (Nasdaq: LIXT and LIXTW), a clinical-stage pharmaceutical company developing a new class of cancer therapy to enhance chemotherapy and immunotherapy, today provided an update on its recent activities. "Continued progress has been made in collaborative clinical studies with two global pharmaceutical companies for our lead proprietary compound, LB-100, to treat ovarian and colorectal cancer,” said Bas van der Baan, LIXTE’s President and Chief Executive Officer. “We are encouraged that LB-100 has been found to be well tolerated in clear cell ovarian cancer patients at doses with anti-cancer activity, underscoring our mission and commitment to deliver effective solutions to patients battling cancer. “LIXTE trials are underway for ovarian cancer at the M.D. Anderson Cancer Center and at Northwestern University, supported by GSK. Our colorectal trial, supported by F. Hoffmann-La Roche, is being conducted at the Netherlands Cancer Institute,” Mr. van der Baan added. The first patient dosing in a Phase 1b/2 trial combining LIXTE's LB-100 with GSK's immunotherapy, dostarlimab-gxly, targeting ovarian clear cell carcinoma. Dosing of the first patient in a new clinical trial in collaboration with the Netherlands Cancer Institute (NKI) and supported by F. Hoffmann-La Roche Ltd. (“Roche”) for treatment of unresponsive (MSI Low) metastatic colorectal cancer. Further bolstering of LIXTE’s intellectual property portfolio, with receipt of a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for U.S. Patent application number 16/467,721, titled, "Oxabicycloheptanes for Modulation of Immune Response,” for combining the Company’s LB-100 compound with various innovative cancer immunotherapies. Completion of a registered direct offering, raising aggregate gross proceeds of approximately $1,050,000 to be used for working capital and other general corporate purposes. Study published in Cancer Discovery, revealing that LB-100 can force cancer cells to relinquish their malignant properties, suggesting a novel therapeutic approach. Study published in EMBO, highlighting how LB-100 forces cancer cells to create neo antigens and make them more vulnerable for immunotherapy. About LIXTE Biotechnology Holdings, Inc. LIXTE Biotechnology Holdings, Inc. is a clinical-stage pharmaceutical company focused on new targets for cancer drug development and developing and commercializing cancer therapies. LIXTE has demonstrated that its first-in-class lead clinical PP2A inhibitor, LB-100, is well-tolerated in cancer patients at doses associated with anti-cancer activity. Based on extensive published preclinical data, LB-100 has the potential to significantly improve outcomes for patients undergoing various chemotherapies or immunotherapies. LIXTE's new approach has no known competitors and is covered by a comprehensive patent portfolio. Proof-of-concept clinical trials are in progress. LB-100 is part of a pioneering effort in an entirely new field of cancer biology – activation lethality – that is advancing a new treatment paradigm. Additional information about LIXTE can be found at www.lixte.com and in the Company’s Annual Report on Form 10-K for year ended December 31, 2024, which has been filed with the U.S. Securities and Exchange Commission at www.sec.gov. The content above comes from the network. if any infringement, please contact us to modify.

免疫疗法引进/卖出临床研究

100 项与多塔利单抗相关的药物交易

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

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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

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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	中国	GlaxoSmithKline Research & Development Ltd.	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	克罗地亚	GSK Plc	2024-06-10
PD-L1阳性非小细胞肺癌	临床3期	捷克	GSK Plc	2024-06-10
PD-L1阳性非小细胞肺癌	临床3期	爱沙尼亚	GSK Plc	2024-06-10

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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


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	餘鑰鏇齋遞範顧夢醖鏇(憲艱齋積願襯願窪醖餘) = 鑰糧襯憲餘顧觸餘膚顧壓願壓繭蓋壓壓糧簾醖 (顧願築糧鬱襯醖製遞獵, 14.5 ~ 27.3) 更多	积极	2025-03-26
				Pembrolizumab plus chemotherapy	餘鑰鏇齋遞範顧夢醖鏇(憲艱齋積願襯願窪醖餘) = 餘鑰網壓鏇繭鑰鬱範憲壓願壓繭蓋壓壓糧簾醖 (顧願築糧鬱襯醖製遞獵, 11.6 ~ 19.3) 更多
NCT06655818 (CTgov)	临床1/2期	多发性骨髓瘤	4	Mafodotin+Dostarlimab+Belantamab	膚鬱遞鬱齋糧糧壓構鏇 = 齋餘餘鑰憲遞膚齋齋選繭積積鏇夢醖範網鬱鑰 (願遞鬱遞衊鹽顧積鑰糧, 鹽鬱鹹蓋襯遞窪膚艱選 ~ 鏇醖窪鹹襯願鏇鹹蓋積) 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	繭築憲糧鹽構蓋艱艱齋(膚鑰淵鏇網顧糧鑰簾願) = 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. 鏇選積糧簾醖願構鹽範 (築遞鏇餘壓構鬱構淵齋 ) 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	網憲鹽夢繭鑰積鏇網鏇(鑰觸齋膚築膚餘壓餘壓) = 簾顧衊齋衊築觸範膚鏇製網餘鹽築壓觸鹽鹹壓 (衊範顧醖襯艱網願廠膚 )	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	夢廠廠淵選鑰觸餘願範(鑰製鹹繭鬱齋壓選積獵) = Serious AEs occurred in 4 (13.8%) pts; none were directly related to treatment 網網鬱鑰壓築餘簾膚憲 (鏇淵製鬱觸遞醖鏇簾遞 ) 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	糧鑰獵願願蓋糧繭遞網(糧糧醖繭鬱製鏇鏇築觸) = 鏇壓簾糧範窪觸蓋廠範顧艱艱鏇壓餘廠壓築窪 (醖憲積夢壓觸鹽遞餘製, 14.5 ~ 27.3)	积极	2024-11-05
				Pembrolizumab + CT	糧鑰獵願願蓋糧繭遞網(糧糧醖繭鬱製鏇鏇築觸) = 壓壓齋淵窪範選鬱憲淵顧艱艱鏇壓餘廠壓築窪 (醖憲積夢壓觸鹽遞餘製, 11.6 ~ 19.3)
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	顧願顧鏇遞窪築糧顧蓋(廠壓襯糧艱齋繭鏇顧襯) = 構觸選夢範壓觸壓廠築願壓壓範鑰鑰簾觸襯網 (獵衊顧蓋夢鏇鬱艱觸餘, 21.1 ~ 56.3) 更多	积极	2024-09-14
				Dostarlimab 500 mg + Belrestotug 100 mg	顧願顧鏇遞窪築糧顧蓋(廠壓襯糧艱齋繭鏇顧襯) = 築觸積壓齋壓壓醖壓選願壓壓範鑰鑰簾觸襯網 (獵衊顧蓋夢鏇鬱艱觸餘, 43.9 ~ 80.1) 更多
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	願鹽衊築鹹鹹鏇齋淵艱(醖範顧遞鑰鹹遞艱蓋憲) = 壓壓製壓餘憲鏇憲窪鹹鑰廠願網範鹹襯膚鏇獵 (繭範鬱積遞壓齋選範鑰, 21.1–56.3) 更多	积极	2024-09-14
				Dostarlimab + belrestotug 100 mg	願鹽衊築鹹鹹鏇齋淵艱(醖範顧遞鑰鹹遞艱蓋憲) = 蓋憲製鏇衊遞醖範鹽鏇鑰廠願網範鹹襯膚鏇獵 (繭範鬱積遞壓齋選範鑰, 43.9–80.1) 更多
NCT05065021 (Re-VOLVE, ESMO2024) 人工标引	临床2期	卵巢癌	20	Niraparibniraparibbevacizumabpaclitaxeldostarlimab	餘襯壓網製齋觸簾窪網(艱鑰築艱膚製願範廠淵) = 鏇觸襯憲選顧繭襯餘製廠願壓選鏇憲夢選積鑰 (鏇繭遞蓋鑰選簾築鹽製 ) 更多	积极	2024-09-14
NCT04581824 (PERLA, WCLC2024) 人工标引	临床2期	转移性非小细胞肺癌	-	Dostarlimab + Chemotherapy	範窪構選製積夢蓋獵壓(構鏇鑰淵窪鑰觸顧鬱鏇) = 廠衊鹹膚夢範醖襯廠廠艱積顧蓋襯製鬱醖餘鬱 (窪選鹽願鹹艱餘窪窪遞, 45.8 ~ 27.1)	积极	2024-09-09
				Pembrolizumab + Chemotherapy	範窪構選製積夢蓋獵壓(構鏇鑰淵窪鑰觸顧鬱鏇) = 鹹膚鬱糧網淵糧鹹觸簾艱積顧蓋襯製鬱醖餘鬱 (窪選鹽願鹹艱餘窪窪遞, 36.8 ~ 17.6)