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更新于：2026-11-04

Durvalumab

度伐利尤单抗

更新于：2026-11-04

概要

基本信息

药物类型

单克隆抗体

别名

Durvalumab (Genetical Recombination)、Durvalumab (genetical recombination) (JAN)、Durvalumab (USAN/INN)

+ [10]

靶点

PDL1

作用方式

抑制剂

作用机制

PDL1抑制剂(程序性死亡配体1抑制剂)

治疗领域

肿瘤消化系统疾病呼吸系统疾病+ [12]

在研适应症

非肌层浸润性膀胱肿瘤胃癌早期胃癌+ [192]

非在研适应症

急性髓性白血病肺腺癌前列腺腺癌+ [103]

原研机构

在研机构

+ [19]

非在研机构

Fred Hutchinson Cancer Research Center

AVEO Pharmaceuticals, Inc.

MedPacto, Inc.

+ [7]

权益机构

MedImmune Pharma BV

Ultimovacs ASAVall d'Hebron Institut d'Oncologia

+ [14]

最高研发阶段批准上市

首次获批日期

美国 (2017-05-01),

尿路上皮癌

最高研发阶段(中国)批准上市

特殊审评加速批准 (美国)、孤儿药 (美国)、孤儿药 (日本)、孤儿药 (澳大利亚)、优先审评 (澳大利亚)、优先审评 (美国)、突破性疗法 (美国)

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结构/序列

Sequence Code 10069506H

来源: *****

Sequence Code 13384675L

来源: *****

关联

942

项与度伐利尤单抗相关的临床试验

NCT07639528

/ Not yet recruiting临床2期IIT

Phase II, Open Label, Non-Randomized, Study of Optimal Preoperative Therapy for Intrahepatic Cholangiocarcinoma (OPTIC)

This phase II trial tests the safety and effectiveness of preoperative immunotherapy with durvalumab and chemotherapy with cisplatin and gemcitabine with or without futibatinib targeted therapy in treating patients with intrahepatic cholangiocarcinoma that can be removed by surgery (resectable). Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Futibatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving immunotherapy with durvalumab and chemotherapy with cisplatin and gemcitabine and/or targeted therapy with futibatinib before surgery may make the tumor smaller for resection and may help prevent the cancer from coming back. Patients whose molecular profiling test result show a genetic change called FGFR2 fusion, rearrangement, or activating mutation, receive immunotherapy, chemotherapy and targeted therapy while patients without a FGFR2 fusion, rearrangement, or activating mutation just receive immunotherapy and chemotherapy. Giving targeted therapy based on molecular profile test results prior to attempted resection for patients with intrahepatic cholangiocarcinoma that has a risk for either not being able to be removed or for coming back after it has been removed may help improve treatment outcomes in patients with resectable intrahepatic cholangiocarcinoma.

开始日期2027-12-10

申办/合作机构

Northwestern University

[+1]

NCT07168668

/ Not yet recruiting临床2期IIT

EXploring Clinical Efficacy of Partial Immune-boost TACE in unrEseCTable HCC Patients Under Systemic Treatment (EXPECT Trial)

Study Objectives： Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) combined with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) or Durvalumab (anti-programmed death-ligand 1; anti-PD-L1) combined with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4; anti-CTLA4) have recently been established as a standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). However, its objective response rate (ORR) is only less than 27% (1, 2), and the majority of patients died of HCC progression and liver failure. Therefore, there is an urgent need to develop a novel combination treatment strategy to overcome resistance to immunotherapy and improve patient outcomes.
Transarterial chemoembolization (TACE) remains the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC) (3, 4). However, in our previous retrospective study (5-7), the investigators consistently observed that this combination not only improves therapeutic responses but also significantly prolongs patient survival. The tumor necrosis caused by TACE may enhance the efficacy of systemic therapies by promoting the release of neoantigens, thereby stimulating immune responses (8-14). This concept has been substantiated in two recent trials involving intermediate-stage HCC (15, 16), where the addition of immune checkpoint inhibitors to TACE resulted in improved clinical outcomes. Nevertheless, this promising approach has yet to replace the decades-old standard treatment protocols, underscoring the need for further proof-of-concept studies.
Both immunotherapy (atezolizumab/bevacizumab or durvalumab/tremelimumab) and transarterial chemoembolization (TACE) are approved treatment modalities for unresectable hepatocellular carcinoma (HCC) by the U.S. and Taiwan Food and Drug Administration (FDA). This phase II non-randomized trial is designed to prospectively evaluate the therapeutic efficacy, safety, and immunological responses in patients with unresectable HCC treated with a combination of immunotherapy and TACE. A particular focus of this study is to explore the potential immune-boosting effects of TACE, including its ability to enhance antigen presentation and stimulate anti-tumor immune responses.

开始日期2027-02-01

申办/合作机构

长庚纪念医院

NCT05403723

/ Suspended临床1期IIT

A Phase 1b Trial of Adaptive Stereotactic Body Radiotherapy in Combination With Durvalumab (MEDI4736), Platinum, and Etoposide in Extensive Stage Small Cell Lung Cancer

This is trial studying the safety of adaptive stereotactic body radiotherapy (SBRT) combined with durvalumab immunotherapy, platinum chemotherapy, and etoposide chemotherapy in platinum refractory extensive stage small cell lung cancer (SCLC).

开始日期2027-01-30

申办/合作机构

University of Maryland Baltimore

[+1]

100 项与度伐利尤单抗相关的临床结果

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100 项与度伐利尤单抗相关的转化医学

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100 项与度伐利尤单抗相关的专利（医药）

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2,567

项与度伐利尤单抗相关的文献（医药）

2026-12-31·ANNALS OF MEDICINE

Dose-Registered CT assessment of radiation-induced lung injury after chemoradiotherapy for stage III NSCLC

Article

作者: Sugahara, Shinji ; Ikeda, Norihiko ; Itonaga, Tomohiro ; Okubo, Mitsuru ; Zama, Tatsuhiko ; Mikami, Ryuji ; Saito, Kazuhiro

AIMS:

To quantify radiation-induced lung injury (RILI) on deformably registered CT images after chemoradiotherapy (CCRT) for stage III NSCLC, and to evaluate spatial and dosimetric associations between RILI and planned dose distribution in a pre-durvalumab cohort.

METHODS:

This retrospective study included 58 patients with stage III NSCLC treated with CCRT using three-dimensional conformal radiotherapy (3D-CRT) prior to the era of consolidation immunotherapy. Follow-up CT images at 6 months (acute) and 12 months (late) were registered to treatment planning CT using deformable image registration (DIR). RILI was quantified by segmented volume (mL) and isodose-line overlap (%). Dosimetric parameters (V5Gy-V60Gy, mean lung dose) and symptomatic RILI (CTCAE grade ≥2) were analysed using correlation, ROC, and logistic regression methods.

RESULTS:

Symptomatic RILI occurred in 14 patients (24.1%). RILI volume decreased by 27.7% from the acute to the late phase, with moderate-to-strong dose-volume correlations in both phases (Spearman ρ = 0.69-0.76). Symptomatic patients showed broader spatial spread into lower-dose regions (median isodose-line overlap 20% vs 40%; p < 0.001). Acute-phase RILI reaching the ≤25% isodose line (≤16.5 Gy) was an exploratory imaging marker in this cohort (AUC 0.81) that remained associated with symptomatic RILI on multivariable analysis (p < 0.01).

CONCLUSIONS:

Dose-registered CT analysis demonstrated consistent spatial associations between planned dose and RILI, providing a hypothesis-generating dosimetric-radiographic reference dataset that requires external validation in IMRT/VMAT- and durvalumab-treated cohorts before clinical application.

2026-12-31·OncoImmunology

Pooled analysis of 2 clinical trials of first-line chemoimmunotherapy for metastatic microsatellite stable colorectal cancer MEDITREME and METIMMOX studies

Article

作者: Ilie, Alis ; Truntzer, Caroline ; Flatmark, Kjersti ; Peroz, Morgane ; Derangère, Valentin ; Rageot, David ; Ree, Anne Hansen ; Bousquet, Paula Anna ; Thibaudin, Marion ; Meltzer, Sebastian ; Ghiringhelli, François

BACKGROUND:

Colorectal cancer with microsatellite stable (MSS) status is intrinsically resistant to immune checkpoint inhibitor monotherapy targeting PD-1 or PD-L1. However, emerging evidence suggests that chemotherapies may overcome this resistance when combined with immunotherapy.

METHODS:

We conducted a pooled analysis of individual patient data from two phase II trials evaluating oxaliplatin-based chemotherapy combined with checkpoint inhibitors as first-line treatment for MSS metastatic colorectal cancer. The MEDITREME trial is a single-arm study assessing durvalumab and tremelimumab with oxaliplatin-based chemotherapy, while the METIMMOX trial is a randomized study comparing standard oxaliplatin-based chemotherapy with an alternating regimen of oxaliplatin-based chemotherapy and nivolumab. We compared overall survival (OS), progression-free survival (PFS), and response rates between patients treated with chemotherapy alone versus chemoimmunotherapy, and evaluated the association between these outcomes and transcriptomic and immunoscore data.

RESULTS:

A total of 130 patients were included: 38 who received chemotherapy alone and 92 chemoimmunotherapy. The median OS was significantly improved in the chemoimmunotherapy group compared with chemotherapy alone (not reached vs. 15.3 months; HR = 0.58; 95% CI, 0.36-0.96; p = 0.03). The complete response rates were higher with chemoimmunotherapy (14% vs. 5%). No significant differences were observed in PFS. High baseline CD8⁺ T-cell infiltration was associated with improved outcomes in patients receiving chemoimmunotherapy but not in those treated with chemotherapy alone.

CONCLUSIONS:

This pooled analysis provides compelling evidence supporting the clinical benefit of first-line chemoimmunotherapy in a subset of patients with MSS mCRC. Baseline CD8⁺ T-cell infiltration may serve as a predictive biomarker for identifying patients most likely to benefit from this treatment approach.

2026-12-31·OncoImmunology

Circadian timing of first-line chemoimmunotherapy is associated with survival in extensive-stage small cell lung cancer

Article

作者: Engin Delipoyraz, Ebru ; Fidan, Sena ; Cakir, Tansel ; Terzioglu, Cihat ; Cakan Demirel, Burcin ; Muglu, Harun ; Kutlu, Yasin ; Hamdard, Jamshid ; Ozcelik, Hakan ; Seker, Mesut ; Sunger, Erdem ; Yucel, Mehmet Haluk ; Bilici, Ahmet ; Acıkgoz, Ozgur ; Mildanoglu, Maral Martin

Growing evidence suggests that circadian timing influences the efficacy of immune checkpoint inhibitors across multiple malignancies. However, evidence in extensive-stage small cell lung cancer (ES-SCLC) remains limited to a single East Asian cohort, and independent validation in other populations is lacking. We conducted a retrospective single-center cohort study of 107 patients with ES-SCLC treated with first-line platinum-etoposide plus atezolizumab or durvalumab. The time of day of administration (ToDA) was defined as the median start time of the first four immunotherapy infusions, and patients were categorized according to the cohort median ToDA. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The cohort median ToDA was 11:54. Patients treated before the median ToDA had significantly longer median PFS (9.07 vs. 7.23 months, p = 0.002) and OS (21.17 vs. 11.43 months, p = 0.002) than those treated later. In multivariable Cox regression analysis, later administration remained independently associated with shorter PFS (adjusted HR 1.63, 95% CI 1.03-2.58; p = 0.038) and OS (adjusted HR 1.65, 95% CI 1.00-2.71; p = 0.049), whereas objective response rates, treatment-related toxicity, and immune-related adverse events were comparable between groups. Morning administration of first-line chemoimmunotherapy was associated with significantly longer survival without increased toxicity in patients with ES-SCLC. These findings support growing evidence that circadian timing may influence immune checkpoint inhibitor efficacy and warrant prospective evaluation of treatment timing as a readily modifiable strategy to optimize immunotherapy delivery.

3,887

项与度伐利尤单抗相关的新闻（医药）

15 小时之前

·药学进展

独家原创 | 靶向代谢物感应G蛋白偶联受体的肿瘤免疫治疗药物临床研究进展

“ 点击蓝字关注我们靶向代谢物感应G蛋白偶联受体的肿瘤免疫治疗药物临床研究进展 PPS 何佳成1，程志远2，杨新宇2，肖晶1，张露3，刘明耀1，2，4，卢伟强1，4* （1.海南医科大学（海南省医学科学院）新药研发与转化中心，海南海口571199；2.华东师范大学生命科学学院，上海 200241；3.海南医科大学第二附属医院临床医学研究所，海南海口570311；4.海南医科大学（海南省医学科学院）药学院/热带药物创新与转化教育部工程研究中心/海南省热带药用植物研究开发重点实验室/海口市黎族医药重点实验室，海南海口571199）卢伟强研究员、博士生导师，国家级高层次青年人才。现任海南医科大学（海南省医学科学院）药学院副院长、课题组长。主要从事药理学研究，聚焦GPCR调控肿瘤免疫的作用机制解析与新药发现。以通信作者身份在Nat Immunol、Nat Commun 、EMBO Mol Med、 Cell Chem Biol、 Cell Rep 和J Med Chem等国际知名期刊发表论文50余篇；获国内外授权发明专利6项。主持创新药物研发国家科技重大专项子课题、国家自然科学基金、上海市东方英才计划青年项目等10余项课题。获第二十二届中国药理学会青年药理学家奖，兼任中国药理学会生化与分子药理学专业委员会委员。作为主要发明人研发新型肿瘤微环境免疫调节剂YY001，该药物已获国家药品监督管理局临床试验批件，正在开展Ⅱ期临床试验。 [摘要] G蛋白偶联受体（G protein-coupled receptor ，GPCR）是人体基因组中最大的跨膜信号转导受体家族，在肿瘤等重大疾病的发生发展进程中发挥关键调控作用。近年来研究表明，代谢物感应GPCR可特异性识别并感应多种肿瘤相关代谢产物，激活免疫抑制信号，进而诱导肿瘤免疫逃逸及耐药，现已成为肿瘤免疫治疗领域的前沿靶点。阐述以前列腺素受体和腺苷受体为代表的代谢物感应GPCR驱动肿瘤免疫逃逸的作用机制。同时，重点梳理靶向这两类受体的药物研发成果与最新临床研究进展，深入分析这两类靶向药物在临床转化过程中面临的机遇与挑战，以期为新一代肿瘤免疫治疗药物的研发提供新视角与新思路。免疫疗法已成为继手术、放疗、化疗之后的第四大肿瘤治疗手段。其中，免疫检查点抑制剂（immune checkpoint inhibitor ，ICI）在多种恶性肿瘤的临床治疗中展现出长期生存获益[1]。然而，目前ICI疗法的总体响应率仍不足30%，多数患者会出现原发性或获得性耐药问题[2]。肿瘤代谢重编程是肿瘤重要的生物学特征之一，该过程伴随着多种代谢产物的异常累积[1]。这些代谢产物多具免疫调节活性，不仅能促进肿瘤相关巨噬细胞（tumor- associated macrophage， TAM）、调节性T细胞（regulatory T cell， Treg 细胞）及髓源性抑制细胞（myeloid-derived suppressor cell， MDSC）等免疫抑制性细胞的募集与活化，也能削弱CD8+T细胞的活化水平及杀伤功能[3]。上述机制共同构筑阻碍抗肿瘤免疫应答的“代谢屏障”，介导肿瘤对免疫疗法的原发性和获得性耐药。因此，靶向干预代谢产物介导的免疫应答受损，已成为提升现有免疫疗法临床疗效、拓展其临床应用的前沿研究方向。 G蛋白偶联受体（G protein-coupled receptor，GPCR）作为人类基因组中最大的跨膜信号转导蛋白超家族，能够识别并响应多种胞外信号分子，通过G蛋白启动下游信号级联反应，参与调控几乎所有的机体生理病理过程。GPCR信号通路的异常活化已被证实为肿瘤等重大疾病发生发展的重要分子病理基础[4]。一方面，众多GPCR家族成员在肿瘤细胞及肿瘤微环境（tumor microenvironment，TME）免疫细胞中呈现异常高表达；另一方面，GPCR的多种内源性配体往往在TME中异常蓄积。这两类机制协同作用，进而形成自分泌或旁分泌的正向反馈环路，导致肿瘤组织内GPCR信号通路持续处于异常活化状态。GPCR异常活化不仅可直接促进肿瘤细胞的增殖、存活、迁移与侵袭，还可通过重塑肿瘤免疫微环境，驱动肿瘤恶性进展，诱发治疗耐药[4]。随着代谢重编程被证实为肿瘤关键生物学特征，以小分子代谢物为内源性配体的GPCR，即代谢物感应GPCR，正逐渐成为肿瘤生物学领域的重点研究方向。该受体家族包括羟基羧酸受体、琥珀酸受体、E型前列腺素受体（E-type prostanoid receptor， EP）家族[主要内源性配体为前列腺素E2（prostaglandin E2，PGE2）]及腺苷受体（adenosine receptor ，AR）家族等，能够感知TME的代谢物水平，并调控免疫细胞功能，进而参与调节抗肿瘤免疫应答。基于代谢物感应GPCR在肿瘤代谢与免疫交叉调控中的重要作用及良好的可药性，这类受体已成为肿瘤治疗领域的新兴热门靶点。其中，EP家族与AR家族是目前肿瘤免疫治疗领域研究最为深入的代谢物感应GPCR，多款靶向这两类受体的候选药物已进入临床研究阶段。本文聚焦上述两类受体，概述其调控抗肿瘤免疫应答的作用机制，并全面梳理相关靶向药物的最新临床研究进展。 1 EP2/EP4受体在肿瘤免疫调控中的功能 PGE2是由花生四烯酸经环氧合酶-2及微粒体前列腺素E合成酶-1催化形成的内源性脂质分子，具有强效的免疫抑制活性[5]。PGE2的生物学功能主要由4种GPCR（EP1-EP4）所介导。EP1受体偶联Gαq/11蛋白，激活磷脂酶Cβ并催化磷脂酰肌醇-4,5-二磷酸水解生成1,4,5-三磷酸肌醇与二酰甘油，进而引发胞内钙流。EP2受体与EP4受体均偶联Gαs蛋白以激活腺苷酸环化酶（adenylyl cyclase ，AC）并促进环磷酸腺苷（cyclic adenosine monophosphate， cAMP）合成。EP3受体偶联Gαi蛋白，可抑制AC活性导致cAMP水平下降（见图1）。其中，EP2受体和EP4受体在肿瘤组织中的巨噬细胞、T细胞等免疫细胞群体中呈异常活化状态，被认为是介导PGE2免疫抑制作用的关键受体。研究表明，EP4受体在肿瘤浸润的巨噬细胞中异常高表达，并与患者的不良预后密切相关[6]。基因敲除与药理学干预实验证实，EP4受体参与调控TAM分化、极化及免疫抑制活性等促肿瘤生物学表型[7]。例如，EP4受体可通过感知PGE2，激活胞内信号转导及转录激活蛋白（signal transducer and activator of transcription， STAT）家族STAT3信号通路，显著上调精氨酸酶-1、白细胞介素-10（interleukin-10，IL-10）等免疫抑制分子的表达，诱导巨噬细胞向免疫抑制性M2表型极化，从而抑制CD8+T细胞的活化和效应功能。靶向阻断EP4受体能够减弱TME中M2型巨噬细胞的免疫抑制功能，促进M1型巨噬细胞活化，使该类髓系细胞由免疫抑制状态转向免疫激活状态，提升CD8+T细胞介导的抗肿瘤免疫应答，阻滞肿瘤进展[7]。此外，PGE2/EP4信号通路可通过激活下游促分裂原活化的蛋白质激酶-细胞外信号调节激酶级联反应，诱导巨噬细胞大量表达并分泌转化生长因子-β,进而降低自然杀伤（natural killer ，NK）细胞对肿瘤细胞的杀伤活性[8]（见图2）。 EP4受体参与负向调控T细胞免疫反应。异常活化的EP4能够下调T细胞功能活性标志物（包括T-bet、穿孔素1及颗粒酶B）的表达，并诱导CD8+T细胞向耗竭表型转化[5]。近年来的单细胞转录组测序研究显示，EP2受体与EP4受体在肿瘤浸润免疫细胞中的表达谱存在重叠，二者均可激活cAMP-蛋白激酶A（protein kinaseA ，PKA）免疫抑制信号，提示这两种受体在免疫调节方面可能存在协同效应。例如，最新研究发现，EP4受体与EP2受体可共同限制干细胞样TCF1+CD8+T细胞的克隆扩增与效应分化，促进肿瘤免疫逃逸。PGE2-EP2/EP4信号轴可下调IL-2受体信号通路，表现为抑制STAT5磷酸化及IL-2受体γ链表达，削弱TCF1+CD8+T细胞对IL-2的应答能力。相应地，特异性敲除编码EP2与EP4的基因可解除上述抑制效应，恢复CD8+T细胞对IL-2的响应，增强其扩增与分化潜能，在多种小鼠模型中表现出较强的抗肿瘤活性[5]。此外，多项研究证实，联合使用EP2受体与EP4受体特异性拮抗剂可产生协同抗肿瘤效果[9]。 2 靶向EP2/EP4受体的药物研究鉴于EP2/EP4受体在驱动肿瘤免疫抑制、抑制机体抗肿瘤免疫应答中的作用，这两类受体已成为肿瘤免疫治疗领域极具开发前景的靶点。EP2受体与EP4受体均具有典型的GPCR七次跨膜螺旋结构，其正构结合口袋在非活性构象下主要面向膜脂双分子层开放，配体通过跨膜螺旋TM1与TM7之间的缝隙从膜内侧侧向进入结合腔。近年来，高分辨率冷冻电镜结构解析进一步揭示了EP2受体与EP4受体在结合腔形状、电荷分布及关键残基上的差异：EP2受体结合腔窄深且底部呈电负性，利于具有长延伸结构的配体深入结合；而EP4受体结合腔宽浅且底部呈电正性，限制了配体的穿透深度。EP2/EP4受体干预分子的设计思路主要围绕结合腔的疏水/极性差异、底部的电负性或电正性特征以及跨膜螺旋的相对位移来优化配体与靶点的适配性[10]（见图3）。目前，已有多个靶向EP4受体和EP2/EP4受体的候选药物被设计开发并进入抗肿瘤临床试验阶段（见表 1）。 2.1 Grapiprant Grapiprant是由辉瑞公司开发的以磺酰脲为结构特征的第1代。受体拮抗剂，其半数抑制浓度（half-maximal inhibitory concentration，IC50）为14nmol·L-1[11]。该药物于2016年作为动物保健药获批上市，用于缓解犬骨关节炎相关疼痛，是首个成功实现商业化的EP4受体拮抗剂。该化合物近年来也被拓展至肿瘤治疗相关研究。目前，grapiprant已完成针对晚期实体瘤患者的Ⅰ期临床试验（NCT03658772）。在Ia、Ib和Ic期临床试验中，分别有64.7%、28.6%和18.8%的患者达到疾病稳定；在200~650mg每日2次的剂量范围内未观察到剂量限制性毒性（dose-limiting toxicity， DLT），上述结果提示grapiprant具有良好的安全性和初步抗肿瘤疗效[12]。 2.2 E7046 E7046是由卫材公司开发的以吡唑环为母核、苯甲酸为结构特征的第2代EP4受体拮抗剂，IC50为13.5nmol·L-1[13]。在肠癌CT26以及乳腺癌4T1等多种移植瘤模型中，E7046均展现出良好的抗肿瘤效果。E7046可显著降低MDSC和M2型TAM在肿瘤组织中的占比，提升M1型TAM及CD8+T细胞的浸润水平[13]。I期临床试验（NCT02540291）结果显示，E7046的半衰期为12h，在125~500mg口服剂量区间内，药物暴露水平随剂量增加呈比例上升；当剂量提升至750mg时，暴露量增长进入平台期，未观察到进一步升高；药物耐受性评价中未观察到DLT，亦未达到最大耐受剂量；接受E7046治疗的患者中，23%实现疾病稳定，主要不良事件为疲劳、腹泻和恶心[14]。 2.3 CR6086 CR6086是由Rottapharm公司开发的以哌啶环为母核、苯甲酸为结构特征的第2代EP4受体拮抗剂，IC50为22nmol·L-1[15]。针对难治性错配修复功能正常/微卫星稳定转移性结直肠癌患者的Ⅰb/Ⅱa期临床试验（NCT05205330）结果显示，CR6086联合程序性死亡受体-1（programmed death-1， PD-1）抗体巴替利单抗可带来一定临床获益。28例受试者中，确认的客观缓解率（objective response rate， ORR）为11%（3例部分缓解），疾病控制率（disease control rate ，DCR）为50%，中位缓解持续时间为7.4个月；中位无进展生存期（progression-free survival， PFS）为2.6个月，中位总生存期（overall survival ，OS）达14.2个月。受试者对该联合治疗方案耐受性良好，试验期间未观察到DLT[16]。 2.4 ONO-4578 ONO-4578是由小野制药开发的以螺环苯并吡喃-环丙烷为母核、烷基酸为结构特征的新型EP4受体拮抗剂，IC50达纳摩尔级[17]。在小鼠肠癌CT26和MC38模型中，ONO-4578可减少TME中M2型TAM浸润，表现出强效抗肿瘤活性。ONO-4578与PD-1抗体在荷瘤小鼠模型中存在协同效应；相较于单药治疗，联合治疗可提升完全缓解率并延长小鼠生存期[18]。目前ONO-4578用于实体瘤的多项临床试验正在进行中。一项评估ONO-4578联合纳武利尤单抗和化疗治疗人表皮生长因子受体2阴性晚期胃癌或胃食管结合部癌的Ⅱ期临床研究（NCT06256328）显示：ONO-4578联合纳武利尤单抗治疗组中位PFS较安慰剂联合纳武利尤单抗+化疗组显著延长（9.0个月vs6.9个月，HR=0.67，P=0.040）；OS存在获益趋势（中位OS未达到vs12.7个月，HR=0.60）；ORR提升至62.0%（对照组48.7%）；程序性死亡受体配体1（programmed death-ligand 1， PD-L 1）阳性（综合阳性评分≥1）患者获益更为突出，中位PFS达9.9个月（对照组5.7个月，HR=0.52）。ONO-4578联合纳武利尤单抗治疗组常见治疗期间不良事件为腹泻和贫血[19]。 2.5 YY001 YY001是以噻吩并呋喃环为母核的新一代EP4受体拮抗剂，其对EP4的IC50为4.3nmol·L-1[20]。临床前研究显示，YY001在多种小鼠移植瘤和自发肿瘤模型中均具有抗肿瘤效果。无论单药使用还是与PD-1抗体联合给药，YY001均可抑制肿瘤生长并延长荷瘤小鼠生存期[7]。机制研究表明，YY001可降低TME中MDSC和M2型TAM浸润，促进CD8+T细胞与M1型TAM聚集；上调肿瘤坏死因子-α（tumor necrosis factor-α , TNF-α)等促炎因子表达，下调IL-10、IL-6等免疫抑制因子水平，进而重塑肿瘤免疫微环境[7]。YY001已完成Ⅰ期临床试验（NCT06228846），该研究共纳入16例晚期实体瘤患者，未观察到DLT，安全性良好；药效学结果显示，YY001的DCR为46.2%，中位PFS为2.38个月，中位OS为10.12个月，表现出初步抗肿瘤疗效[21]。 2.6 TPST-1495 TPST-1495是由Tempest Therapeutics公司开发的新型EP2/EP4受体双靶点拮抗剂，其对EP2受体和EP4受体的IC50分别为17.21和3.24nmol·L-1，对EP1受体和EP3受体无明显抑制活性[22]。TPST-1495可增加TME中CD8⁺T细胞、NK细胞及树突状细胞（dendritic cell， DC）浸润，诱导抗肿瘤免疫应答。在磷脂酰肌醇-4,5-二磷酸-3-激酶催化亚基α基因突变型头颈部鳞状细胞癌和结直肠癌等多种小鼠肿瘤模型中，TPST-1495可抑制肿瘤生长，并可增强PD-1抗体的治疗效果[22-23]。一项Ⅰ期临床试验（NCT04344795）已完成，该试验旨在评估TPST-1495单药或联合帕博利珠单抗用于晚期实体瘤的最大耐受剂量（maximum tolerated dose，MTD）、推荐Ⅱ期给药剂量（recommended phase 2 dose ，RP2D）、安全性、耐受性、药效学及初步抗肿瘤活性[24]。临床结果显示，单药组与联合组的DCR均约为43%（单药组：19/44；联合组：9/21）。联合组有1例微卫星稳定型结直肠癌受试者达到部分缓解。TPST-1495单药治疗最常见治疗相关不良事件（treatment-related adverse event， TRAE）包括腹泻、腹痛、疲劳及恶心；联合组主要TRAE为恶心、疲劳和腹泻。单药治疗的RP2D确定为50mg每日1次，联合治疗的RP2D仍待进一步评估。 2.7 ACT-1002-4271 除上述已进入抗肿瘤临床试验的分子外，尚有若干EP2/EP4受体双靶点小分子拮抗剂处于临床前研究阶段。ACT-1002-4271为新型EP2/EP4受体双靶点拮抗剂，对EP2受体与EP4受体的IC50分别为6、3nmol·L-1，对EP1受体与EP3受体无显著抑制作用[25]。在EMT-6小鼠乳腺癌模型中，皮下注射ACT-1002-4271可明显抑制肿瘤生长；10只治疗组小鼠中有2只实现肿瘤完全消退。 2.8 TP-18 TP-18为口服有效的强效EP2/EP4受体双靶点拮抗剂，该化合物亲和力与选择性优异，对EP2受体与EP4受体的IC50分别为9.5、3.3nmol·L-1，对EP1受体与EP3受体的选择性超过1 000倍[26]。体内药效结果显示，TP-18可降低V-set免疫球蛋白结构域包含蛋白4高表达的免疫抑制性TAM富集，削弱该髓系亚群的免疫抑制功能。TP-18处理可促使TME由免疫抑制态向免疫激活态转换，提升CD8⁺T细胞在TME中的浸润水平及其肿瘤杀伤能力。在多种结直肠癌小鼠模型中，TP-18单药即可抑制肿瘤生长，并显著增强PD-1抗体疗效，逆转肿瘤免疫治疗耐药。在患者来源肿瘤免疫类器官模型上，TP-18同样可提升PD-1抗体的肿瘤杀伤效果[26]。靶向EP2/EP4受体的干预策略与ICI的抗肿瘤机制存在互补性：EP2/EP4受体拮抗剂可缓解免疫抑制细胞介导的肿瘤免疫抑制效应，ICI则激活T细胞效应功能，二者联用有望实现协同抗肿瘤效果。随着新一代EP2/EP4受体拮抗剂的开发及临床研究推进，该类药物与ICI的联合方案，有望为克服免疫治疗耐药、扩大免疫治疗受益人群提供可选策略。 3 AR在肿瘤免疫调控中的功能腺苷是一类广泛分布于机体的嘌呤核苷，在维持组织稳态及调控炎症反应等生理过程中发挥重要作用。TME中，缺氧、慢性炎症、代谢重编程及致癌通路异常活化等多重因素可诱导腺苷蓄积，使其浓度升至微摩尔级，显著高于生理状态下的纳摩尔级水平[27]。腺苷主要由腺嘌呤核苷酸逐级分解产生。肿瘤坏死细胞可大量释放腺苷三磷酸（adenosine triphosphate，ATP），同时，缺氧、营养匮乏、炎症刺激或抗肿瘤治疗等应激条件，可促进细胞主动向胞外分泌ATP。胞外ATP可经胞外核苷三磷酸二磷酸水解酶1[分化抗原39（cluster of differentiation 39， CD39）]催化生成腺苷一磷酸（adenosine monophosphate， AMP），再经胞外5'-核苷酸酶（CD73）去磷酸化生成腺苷[28]。除经典CD39-CD73生成途径外，机体还存在非经典腺苷合成途径，该途径也参与腺苷积累。外核苷酸焦磷酸酶/磷酸二酯酶1（ectonucleotide pyrophosphatase/phosphodie-sterase 1，ENPP 1）与CD38可协同催化胞外烟酰胺腺嘌呤二核苷酸+转化为AMP，该产物最终在碱性磷酸酶或CD73的水解作用下生成腺苷[29]。腺苷的生物学效应主要由4类特异性GPCR即AR介导，分别为A1、A2A、A2B及A3。其中，A1受体与A3受体偶联Gᵢ蛋白，受体活化后可抑制AC介导的cAMP生成，进而阻断PKA/cAMP反应元件结合蛋白（cAMP response element-binding protein， CREB）信号通路；与之相反，A2A受体与A2B受体可偶联Gₛ蛋白，活化后能够增强AC催化活性，提升胞内cAMP浓度，进而激活PKA/CREB信号通路[27]。A2A受体与A2B受体对腺苷的结合亲和力存在显著差异：A2A为高亲和力受体，解离常数（dissociation constant ，Kd）约为310nmol·L-1；A2B为低亲和力受体，Kd约为15µmol·L-1[27]。A2A受体与A2B受体可通过激活cAMP/PKA/CREB信号轴启动免疫抑制程序，是介导腺苷免疫调节活性的主要受体亚型（见图4）。 TME中，A2A受体广泛表达于T细胞、髓系细胞等多种免疫细胞表面，且TME内多种促癌信号可上调A2A受体表达。研究证实，IL-1家族的IL-1β、IL-18及IL-36等成员可强效诱导CD8+T细胞表达A2A受体[30]。A2A受体异常活化可上调PD-1、T细胞免疫球蛋白黏蛋白3及细胞毒性T淋巴细胞相关抗原4（cytotoxic T lymphocyte-associated antigen- 4， CTLA-4）等免疫检查点分子的表达，同时抑制干扰素-γ与TNF-α等效应分子分泌，阻碍CD8+T细胞的增殖、活化及免疫效应发挥[27]。此外，A2A受体可调控T细胞的代谢过程。A2A受体通过激活cAMP/PKA通路，抑制哺乳动物雷帕霉素靶蛋白复合体1活化，降低细胞糖酵解水平、损伤线粒体功能，进而阻碍外周和肿瘤浸润CD8+T细胞的代谢适应性重塑[31]。 A2A受体同样参与调控髓系细胞的免疫功能。小鼠荷瘤模型研究显示，髓系细胞特异性敲除编码A2A的基因，可显著降低TAM、MDSC及DC中IL-10的表达水平，同时上调TAM表面主要组织相容性复合体Ⅱ及IL-12的表达，进而促进CD8+T细胞与NK细胞活化，增强其抗肿瘤效应，最终抑制肿瘤生长与转移[32]。近期研究发现，前列腺癌肿瘤组织中的分泌型磷蛋白1阳性巨噬细胞可通过释放腺苷激活A2A信号通路，诱导CD8+T细胞功能耗竭，引发肿瘤免疫治疗耐药[33]。临床前动物模型研究证实，A2A受体拮抗剂可有效提升移植瘤对ICI治疗的敏感性[34]。早期临床研究结果表明，A2A受体拮抗剂联合PD-L1抗体可在转移性去势抵抗性前列腺癌（metastatic castration-resistant prostate cancer， mCRPC）患者中产生临床应答[33]（见图4）。相较于研究较为充分的A2A受体，A2B受体因对腺苷亲和力较低，其肿瘤免疫调控功能长期未得到充分关注，近年多项研究证实，A2B受体同样具有关键的免疫调节作用。研究发现，激动型4-1BB抗体可特异性下调CD8+T细胞中A2B受体表达，对A2A受体表达无明显调控作用[35]。敲除编码A2B的基因可增强谷胱甘肽/谷胱甘肽过氧化物酶4介导的抗氧化反应，使经激动型4-1BB抗体处理的CD8+T细胞获得更强的存活与扩增优势，进而提升其抗肿瘤活性[35]。腺苷可进一步分解为嘌呤，嘌呤能信号能够通过P2Y受体（P2Y receptor ，P2YR）家族成员参与肿瘤免疫调控。其中，P2Y2R可通过结合αV整合素，阻滞T细胞和巨噬细胞向口腔鳞状细胞癌微环境浸润，促进TME形成免疫抑制状态[36]。P2Y6R可依赖尿苷二磷酸激活TAM，诱导TAM向M2型促肿瘤表型极化，抑制CD8+T细胞的募集和活化，削弱机体抗肿瘤免疫应答，最终介导ICI治疗耐药[37]。在药物研发方面，目前靶向P2Y2R和P2Y6R的抗肿瘤候选药物仍处于早期发现及临床前研究阶段，尚无相关药物进入抗肿瘤临床试验。 4 靶向A2A/A2B受体抗肿瘤药物临床研究进展 A2A/A2B受体已成为肿瘤免疫治疗领域广受关注的重要靶点。A2A/A2B受体同属A类GPCR，二者正构结合口袋均位于跨膜螺旋簇之间，具有高度相似的保守结合模式。A2A/A2B受体结合口袋均以保守残基N2536.55（A2A）、N2546.55（A2B）为关键氢键锚点，配体需与该残基形成氢键供体或氢键受体相互作用，方可实现与受体的稳定结合[38-39]。在此基础上，两类受体的结合口袋特征存在一定差异：A2A受体结合腔分布有特异性疏水口袋，配体可通过引入疏水基团以占据该区域并置换结合口袋内水分子，进而提升配体与受体的结合亲和力[38]；A2B受体激动剂BAY60-6583可与T893.36等残基形成额外氢键相互作用，进一步稳定配体-受体复合物[39]。上述结构特征为研发高活性、高选择性的A2A/A2B受体靶向小分子干预药物提供了重要的结构基础（见图5）。目前，全球已有多款高选择性A2A受体拮抗剂、A2B受体拮抗剂及A2A/A2B受体双靶点拮抗剂完成研发，且均进入Ⅰ/Ⅱ期临床试验阶段（见表2）。 4.1 CPI-444 CPI-444是Corvus Pharmaceuticals公司研发的以三唑并嘧啶为母核的小分子A2A受体拮抗剂，该药物对A2A受体的抑制常数（inhibition constant，Ki）3.54nmol·L-1，对A2A受体的选择性较其他腺苷受体亚型高出50倍以上[34]。在小鼠结直肠癌移植肿瘤模型中，CPI-444与PD-L1抗体、CTLA-4抗体的联合给药方案，可有效诱导肿瘤病灶消退，并上调瘤内CD8+T细胞浸润水平[34]。CPI-444针对转移性肾细胞癌等实体瘤的Ⅰ/Ⅰb期临床试验（NCT-02655822）已完成，该研究系统评估了其单药及联合PD-L1抗体阿替利珠单抗治疗的安全性、耐受性与抗肿瘤活性。试验结果显示，CPI-444单药治疗组ORR为3%，仅1例患者达到部分缓解；联合治疗组ORR为11%，共4例患者达到部分缓解[40]。 4.2 AZD4635 AZD4635是AstraZeneca公司开发的一种基于1,2,4-三嗪骨架的A2A受体拮抗剂（Ki=1.7nmol·L-1）[38]。在小鼠纤维肉瘤MCA205模型中，AZD4635单药（50mg·kg-1）可显著抑制肿瘤生长，肿瘤生长抑制率（tumor growth inhibition ，TGI）达68%；与PD-L1抗体联合给药时可完全抑制肿瘤生长（TGI=100%）[38]。一项I期临床试验（NCT-02740985）评估了AZD4635单药或联合PD-L1抗体德瓦鲁单抗在mCRPC患者队列中的安全性、药代动力学特征和初步抗肿瘤活性[41]。该研究共纳入94例既往未接受过ICI疗法的mCRPC患者，其中49例接受AZD4635单药治疗（75mg或100mg，每日1次），45例接受AZD4635联合德瓦鲁单抗治疗。疗效数据显示，单药组确认的ORR为6.1%，共2例患者达到部分缓解，联合治疗组ORR提升至16.2%，包括2例完全缓解和4例部分缓解；单药组前列腺特异性抗原50应答率为6.4%，联合治疗组为20.0%。生物标志物分析结果表明，外周血腺苷基因特征高表达患者的中位PFS为21周，显著优于低表达患者的8.7周。整体而言，AZD4635单药及联合治疗方案均具有良好的用药耐受性。 4.3 EOS-850 EOS-850是iTeos Therapeutics公司研发的基于噻唑并三唑并嘧啶稠环骨架的口服型A2A受体拮抗剂，该药物可通过阻断腺苷介导的T细胞免疫抑制效应，激活机体抗肿瘤免疫应答[42]。目前EOS-850已有多项针对晚期实体瘤的临床试验正在进行。其单药治疗晚期实体瘤的I期临床试验（NCT03873883）数据显示，80mg、每日2次的给药剂量具有良好的整体耐受性。该研究纳入42例接受过多线系统治疗（中位治疗线数为3线）的晚期实体瘤患者，共观察到2例确认的部分缓解病例，分别为黑色素瘤和前列腺癌患者，截至数据统计节点，2例患者的缓解持续时间均超过230d；另有12例患者最佳疗效评估为疾病稳定，其中3例患者疾病稳定持续时间超过6个月。免疫组化检测结果显示，肿瘤组织A2A受体高表达患者的临床获益更显著，提示A2A受体可作为预测该药物疗效的潜在生物标志物。试验TRAE包括疲劳、恶心和便秘，未发现严重不良事件[43]。 4.4 TT-4 TT-4是Tarus Therapeutics公司研发的高活性A2B受体拮抗剂，目前该药物分子结构尚未公开披露。在小鼠乳腺癌4T1模型中，TT-4单药治疗（3mg·kg-1，口服，每日2次）可显著抑制肿瘤增殖，其抑瘤效果优于PD-1抗体单药治疗。机制研究表明，TT-4可阻断TME中腺苷对A2B受体的激活作用，减少MDSC的肿瘤浸润，进而促进T细胞活化，最终实现对肿瘤进展的抑制[44]。ADPORT-601研究（NCT04969315）为针对TT-4开展的多中心、开放标签I期首次人体临床试验，旨在评估该药物在晚期实体瘤患者中的安全性、耐受性、药代动力学特征和初步抗肿瘤活性。根据2024年美国临床肿瘤学会年会公布的试验方案，TT-4单药队列纳入对象为经标准治疗耐药的晚期结直肠癌、非小细胞肺癌、子宫内膜癌及卵巢癌患者。研究采用3+3剂量递增试验设计，后续将逐步开展单药扩展队列及联合用药队列研究。 4.5 AB928 AB928是Arcus Bioscience公司研发的基于嘧啶-三氮唑-吡啶骨架的A2A/A2B受体双靶点拮抗剂，该药物对A2A受体和A2B受体的Kd分别为1.4和2nmol·L-1[45]。在TME中，AB928可竞争性阻断肿瘤分泌的腺苷与T淋巴细胞、巨噬细胞、DC和NK细胞等免疫细胞表面A2A受体及A2B受体的结合，解除腺苷-A2A/A2B信号通路介导的免疫抑制状态，激活机体抗肿瘤免疫反应。目前AB928用于多种实体瘤的Ⅰb/Ⅱ期临床试验正在开展。随机对照Ⅱ期ARC-9研究（NCT04660812）纳入112例经奥沙利铂联合伊立替康方案治疗失败的转移性结直肠癌患者，按2∶1比例随机分为联合用药组（AB928+赛帕利单抗+奥沙利铂/氟尿嘧啶/亚叶酸钙+贝伐珠单抗，n=75）与对照组（瑞戈非尼单药，n=37）。研究结果证实，联合用药组相比对照组显示出显著的总生存获益。中位随访20.4个月的临床数据显示，联合用药组中位PFS显著延长（6.2个月vs2.1个月），中位OS亦显著改善（19.7个月vs9.5个月）；联合用药组确认的ORR为17.3%，显著高于对照组的2.7%[46]。 4.6 M1069 M1069是由Merck公司和Domain Therapeutics公司联合开发的以噻唑并[4,5-c]吡啶为骨架的A2A/A2B受体双靶点拮抗剂，其对A2A受体与A2B受体的IC50分别为0.13和9.03nmol·L-1，对A2A、A2B受体的拮抗活性较A1、A3受体高出100倍以上[47]。目前，M1069正在开展针对转移性或局部晚期不可切除实体瘤患者的I期临床试验（NCT05198349），旨在评估M1069的剂量-毒性关系、MTD和推荐扩展剂量。试验初始给药剂量为150mg，每日2次口服，后续梯度递增至300mg、450mg和600mg，每日2次口服，该试验于2022年启动患者招募，计划入组21~30例晚期实体瘤患者。临床试验注册信息显示，该研究已于2023年提前终止，实际仅入组15例患者，最常见不良反应为疲劳和恶心（各33.3%），未观察到客观缓解[48]。M1069的后续临床开发状态尚不明确。 5 总结与展望肿瘤代谢与免疫的交互调控是当前肿瘤学研究的前沿领域，亦是发掘原创抗肿瘤靶标的重要源泉。大量研究证实，代谢物感应GPCR可识别TME中PGE2、腺苷等免疫抑制性代谢产物，促进TAM等免疫抑制性细胞的募集与活化，并诱导CD8⁺T细胞功能耗竭，减弱机体抗肿瘤免疫应答。GPCR信号通路可介导肿瘤代谢重编程与肿瘤免疫抑制的关联过程。近年来，该领域基础研究不断取得突破，推动相关研究成果向临床应用转化。目前，国内外多家制药企业已开发多款靶向EP2/EP4受体及A2A/A2B受体的抗肿瘤候选药物并进入临床研究阶段。初步临床数据显示，此类药物可表现出一定的抗肿瘤活性，且整体安全性与耐受性良好。然而，上述药物单药治疗的临床获益仍较为有限，其在肿瘤综合治疗体系中的应用价值仍有待进一步验证。为推动靶向代谢物感应GPCR的抗肿瘤药物开发，未来的研究可从以下几个方面开展：其一，优化靶向药物分子设计。开发靶向EP2/EP4及A2A/A2B受体的高活性、高成药性拮抗剂，阻断TME中高浓度代谢产物介导的受体持续激活，完全阻断下游抑制性信号，提升机体抗肿瘤免疫应答水平。其二，建立基于生物标志物的精准治疗体系。目前亟需建立多维度、动态化的生物标志物评估体系，通过实时检测肿瘤组织代谢产物含量、GPCR活化水平及免疫细胞功能特征，精准筛选潜在获益患者，动态评估药物治疗效果，改善肿瘤患者临床治疗应答异质性的问题。其三，完善联合治疗方案设计。一方面，拓展代谢物感应GPCR拮抗剂的应用场景，将其与嵌合抗原受体T细胞治疗、干扰素基因刺激因子激动剂等新型免疫疗法联用，将单纯解除免疫抑制的治疗模式升级为主动激活抗肿瘤免疫的治疗模式。另一方面，探索该类药物与临床常规抗肿瘤靶向药物、化疗药物的联合使用方式，扩大临床治疗适用范围。此外，EP2/EP4与A2A/A2B受体拮抗剂均具备良好的临床安全性，将该类药物应用于肿瘤高危人群的化学预防研究，具备较高的前瞻性研究意义与临床转化价值。综上，靶向代谢物感应GPCR已成为肿瘤免疫治疗的新兴研究方向，能够为肿瘤临床治疗提供新的研发思路与治疗方案。参考文献： [1] Aliazis K, Christofides A, Shah R, et al. 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[36]Forti K M, Woods L T, Jasmer K J, et al. Tumoral P2Y2 receptor modulates tumor growth and host anti-tumor immune responses in a syngeneic murine model of oral cancer[J]. Purinergic Signal, 2024, 20(4): 359-370. [37] Scolaro T, Manco M, Pecqueux M, et al. Nucleotide metabolism in cancer cells fuels a UDP-driven macrophage cross-talk, promoting immunosuppression and immunotherapy resistance[J]. Nat Cancer, 2024, 5(8): 1206-1226. [38] Borodovsky A, Barbon C M, Wang Y, et al. Small molecule AZD4635 inhibitor of A2AR signaling rescues immune cell function including CD 103+dendritic cells enhancing anti- tumor immunity[J]. J Immunother Cancer, 2020, 8(2): e000417. [39] Cai H, Xu Y, Guo S, et al. Structures of adenosine receptor A2BR bound to endogenous and synthetic agonists[J]. Cell Discov, 2022, 8(1): 140. [40]Augustin R C, Leone R D, Naing A, et al. Next steps for clinical translation of adenosine pathway inhibition in cancer immunotherapy[J]. 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ESMO OPen, 2026, 11(5): 106962. 本文引文格式：何佳成, 程志远, 杨新宇, 等. 靶向代谢物感应G蛋白偶联受体的肿瘤免疫治疗药物临床研究进展[J]. 药学进展, 2026, 50(8): 701- 712. 美编排版：杨书惠感谢您阅读《药学进展》微信平台原创好文，也欢迎各位读者转载、引用。本文选自《药学进展》2026年第 8 期。《药学进展》杂志由教育部主管、中国药科大学主办，中国科技核心期刊（中国科技论文统计源期刊）。刊物以反映药学科研领域的新方法、新成果、新进展、新趋势为宗旨，以综述、评述、行业发展报告为特色，以药学学科进展、技术进展、新药研发各环节技术信息为重点，是一本专注于医药科技前沿与产业动态的专业媒体。《药学进展》注重内容策划、加强组稿约稿、深度挖掘、分析药学信息资源、在药学学科进展、科研思路方法、靶点机制探讨、新药研发报告、临床用药分析、国际医药前沿等方面初具特色；特别是医药信息内容以科学前沿与国家战略需求相合，更加突出前瞻性、权威性、时效性、新颖性、系统性、实战性。根据最新统计数据，刊物篇均下载率连续三年蝉联我国医药期刊榜首，复合影响因子1.311，具有较高的影响力。《药学进展》编委会由国家重大专项化学药总师陈凯先院士担任主编，编委由新药研发技术链政府监管部门、高校科研院所、制药企业、临床医院、CRO、金融资本及知识产权相关机构近两百位极具影响力的专家组成。联系《药学进展》↓↓↓ 编辑部官网：pps.cpu.edu.cn；邮箱：yxjz@163.com；电话：025-83271227。欢迎投稿、订阅！往期推荐聚焦“第七届药学前沿学术论坛暨《药学进展》编委会会议” 聚力前沿赛道，共启学术新程：第七届药学前沿学术论坛在南京隆重启幕承学术匠心，启时代新章：《药学进展》第七届编委会、第三届青年编委会成立大会在宁召开聚焦“兴药为民·2023生物医药创新融合发展大会”“兴药为民·2023生物医药创新融合发展大会”盛大启幕！院士专家齐聚杭城，绘就生物医药前沿赛道新蓝图“兴药强刊”青年学者论坛暨《药学进展》第二届青年编委会议成功召开“兴药为民·2023生物医药创新融合发展大会”路演专场圆满收官！校企合作新旅程已启航我知道你在看哟

免疫疗法临床1期临床申请

19 小时之前

·Firstwordpharma

Amgen raises full-year outlook after third-quarter beat

After ranking as the third-best-performing pharma in the third quarter, Amgen has now shared its financial results for the three-month period, which handily surpassed analyst expectations (see – Vital Signs: Top performers of the third quarter).Buoyed by strong sales from cholesterol-lowering drug Repatha, as well as lung cancer treatment Imdelltra and autoimmune disease therapy Uplizna, Amgen reported third-quarter revenues of $10.4 billion, up 8% year-over-year and ahead of the Street's $10.1-billion forecast. Its adjusted earnings climbed 14% to $6.45 per share, topping consensus estimates of $5.79. The drugmaker's quarterly results prompted it to bump up its full-year outlook; it now expects adjusted earnings of $22.90 to $23.70 per share on revenues of $38.9 billion to $39.7 billion. Amgen previously guided for its 2026 revenues to fall between $38.2 billion and $39.4 billion, with earnings in the range of $22.30 to $23.50 per share.Despite the beat-and-raise quarter, Amgen's shares fell about 1.5% during after-hours trade on Tuesday.Sales breakdownRepatha, an injectable PCSK9 inhibitor, continued to be Amgen's best-selling product. Despite competition from Merck & Co.'s oral PCSK9 inhibitor Lipfendra, Repatha's sales increased 37% to $1.09 billion, edging out estimates of $1.04 billion. On the company's second-quarter earnings call, management was unfazed by Lipfendra's potential to steal market share away from Repatha, and their bullish sentiment seemed to hold true for the third quarter. Uplizna had the largest year-over-year sales increase, soaring 191% to $451 million, while revenue from Imdelltra jumped 128% to $406 million. The cancer drug recently impressed at last month's European Society for Medical Oncology (ESMO) congress. In the Phase III DeLLphi-305 study, Imdelltra plus AstraZeneca's Imfinzi as a first-line maintenance regimen for patients with extensive-stage small-cell lung cancer cut the risk of death by 58%.Apar Ganti — a professor of medical oncology at the University of Nebraska Medical Center and associate director of clinical research at the school's Fred and Pamela Buffett Cancer Center — described the results as "unprecedented," telling FirstWord, "Large academic centres will be champing at the bit to treat their next patient with this regimen." For more from that interview, see – KOL Views Q&A: SCLC maintenance win for Amgen's Imdelltra too strong to ignore even for logistical holdouts.Other products with year-over-year growth include Evenity (+39%, $751 million), Krystexxa (+31%, $419 million), Tezspire (+43%, $538 million) and Blincyto (+27%, $496 million), while quarterly sales for osteoporosis drug Prolia fell 45% to $632 million, missing analyst expectations of $697 million.

财报临床3期临床结果临床失败

2026-11-04

·BioSpace

Seres Therapeutics Reports Third Quarter 2026 Financial Results and Announces Plans for Advancing Development of SER-155 To Prevent Immune Checkpoint Inhibitor-Related Enterocolitis (irEC)

Prevention approach aims to keep patients on immune checkpoint inhibitor (ICI) therapy and avoid immunosuppressive irEC treatments, representing an additional broad therapeutic opportunity for SER-155 Seres expects to submit plans for the next irEC study design to the FDA in Q1 2027 Study builds on encouraging investigator-sponsored trial (IST) results, in which 12 of 15 participants (80%) with moderate-to-severe irEC achieved an immunosuppressive-free clinical response of diarrhea following treatment with SER-155 CAMBRIDGE, Mass., Nov. 04, 2026 (GLOBE NEWSWIRE) -- Seres Therapeutics, Inc. (Nasdaq: MCRB), (Seres or the Company), a leading live biotherapeutics company, today reported third quarter 2026 financial results and announced it is progressing plans for a next study evaluating SER-155 for the prevention of immune checkpoint inhibitor-related enterocolitis (irEC) in patients initiating immune checkpoint inhibitor (ICI) cancer therapy, which is expected to include a dose optimization component. The Company anticipates submitting the study design to the FDA in the first quarter of 2027. The planned study builds on previously announced positive topline results from an investigator-sponsored trial (IST) conducted at Memorial Sloan Kettering Cancer Center (MSK) in patients with moderate-to-severe irEC, in which 80% of participants achieved an immunosuppressive-free clinical response at Day 15, following treatment with SER-155. SER-155 was well tolerated, with no drug-related serious adverse events observed. irEC is a frequent and debilitating adverse reaction associated with widely used ICI cancer therapy that often requires patients to halt life-saving ICI treatment and begin systemic immunosuppressive corticosteroids. irEC is listed as an adverse reaction in the labels of all approved ICIs, including PD-1 inhibitors (Keytruda ® , Opdivo ® , Zynyz ® ), PD-L1 inhibitors (Imfinzi ® , Bavencio ® ), CTLA-4 inhibitors (Yervoy ® , Imjudo ® ), and LAG-3 inhibitor (Opdualag) - all of which were therapies received by patients in the IST. "The irEC IST provided promising evidence that orally administered SER-155 improved epithelial barrier integrity and reduced gastrointestinal inflammation without systemic immunosuppression and was well-tolerated in patients with ICI-induced enterocolitis, " said Richard Kender, Executive Chairman and Interim Chief Executive Officer of Seres. "Based on those results, and in consultation with key opinion leaders in the field, we determined that developing SER-155 to prevent irEC could address a significant unmet clinical need in patients being treated with ICIs for their cancer. We believe SER-155 may enable ICI patients, of whom there are currently estimated to be approximately 300,000 in the U.S. alone, to remain on their therapy by reducing the occurrence of irEC, which often requires the halting of life-saving cancer treatment. We also think this development approach offers a time and capital efficient path to clinical data and positions SER-155 to potentially address a broad ICI-treated population and look forward to submitting our planned study design to the FDA in the first quarter of 2027. We are pleased to have two oncology-focused programs for SER-155, one with the goal of preventing irEC, and the other, in allogeneic hematopoietic stem cell transplant (allo-HCT), aimed at reducing the risk of bloodstream infections, a leading cause of mortality in these patients. We continue to seek capital through partnerships and other sources to advance our programs in irEC and in allo-HCT, which is Phase 2 ready, pending funding." Recent Highlights SER-155 for the prevention of irEC Seres intends to advance SER-155 into a next study evaluating prophylactic oral administration in patients initiating ICI therapy, with a dose optimization component, dependent on funding. The study is being designed in consultation with leading oncologists and irEC experts. As part of the development program, Seres plans to engage with the FDA to discuss study design and potential endpoints, which could include incidence of irEC (all grades), ICI administration, and safety. In addition, Seres looks forward to receiving FDA feedback on plans to optimize prophylactic dosing for the study, which could include a healthy volunteer study component or a dosing lead-in element, the results of which are expected to inform the prophylactic dosing course, before initiating dosing in the broader ICI population. As in the completed IST, the Company anticipates enrolling patients across a wide range of ICI types. The prevention approach is designed to reduce incidence of irEC, keep patients on ICI therapy and avoid immunosuppressive irEC treatments. irEC is among the most frequent and severe immune-related adverse reactions in patients receiving ICIs, and affects up to 50% of ICI recipients, with rates varying by ICI type and regimen. Current standard of care for moderate or worse irEC (Grade 2 or above) requires halting life-saving ICI therapy and initiating a systemic immunosuppressive corticosteroid, a biologic, or both, which carry their own toxicities and may compromise the anti-cancer effect of ICI therapy. The planned next study builds on encouraging topline results from the open-label IST (NCT06801067) conducted at MSK evaluating SER-155 as a potential treatment in irEC, which Seres reported in July. The study enrolled 15 participants with moderate-to-severe (Grade 2-3) irEC (which represents approximately 25% of all ICI recipients) who were naïve to immunosuppressive therapy; 12 of 15 (80%) of participants treated with SER-155 achieved an immunosuppressive-free clinical response at Day 15, the primary efficacy endpoint, defined as at least a one-grade improvement in diarrhea symptoms without immunosuppressive therapy. Five of 15 participants (33%) achieved immunosuppressive-free complete clinical remission at Day 15. SER-155 was generally well tolerated through Day 43, with no serious adverse events assessed as related to SER-155. In the IST, translational biomarkers of gastrointestinal inflammation and mucosal epithelial barrier integrity both improved following SER-155 treatment, with statistically significant reductions by Day 43. ICIs represent one of the largest and fastest-growing segments of the oncology market, with the worldwide market valued at well over $50 billion in 2025. In the U.S. alone, it is estimated that 300,000 patients are currently on ICIs, representing a large potential target patient population for SER-155 as a preventative treatment for irEC, and a potential multi-billion-dollar commercial opportunity, as the Company believes that both patients and clinicians will be motivated to adopt a prophylactic approach that could permit patients to remain on their ICI therapy. Seres expects to submit the proposed next study design to the FDA in the first quarter of 2027 and engage with the agency thereafter. Seres and MSK will present a poster entitled “High Immunosuppressive-Free Response Rate of irEC with SER-155, an Investigational Oral Live Biotherapeutic, as First-Line Therapy, in a Phase 1b Study” at the Society for Immunotherapy of Cancer (SITC) 2026 Annual Meeting in Phoenix, AZ on November 7, 2026. This poster will highlight the promising results of the IST. Broader pipeline and portfolio SER-155 remains Phase 2 ready for the prevention of bloodstream infections in adults undergoing allo-HCT for the treatment of blood cancer, pending funding. SER-155 has received Breakthrough Therapy and Fast Track designations for this indication. Efforts continue to secure funding to advance clinical development for this program. On November 3, Seres announced that results from its Phase 1b clinical study of SER-155 in adults undergoing allo-HCT were published in Nature Medicine, marking an important milestone for the program and providing recognition of the innovative science being advanced by the Company. The publication reported that SER-155 was generally well tolerated and was associated with a 77% relative risk reduction in BSIs compared with placebo. Seres continues to progress development of SER-428, an investigational oral liquid formulation based on a subset of SER-155 strains supported by a grant from CARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator), for dosing in patients who cannot take oral capsules, including critically ill patients who receive nutrition and medications via feeding tube. Seres is designing a Phase 1b open-label trial, in collaboration with Daniel E. Freedberg, M.D., M.S., of Columbia University, and in consultation with CARB-X, to evaluate SER-428 in patients with sepsis who are receiving antibiotics in the Medical Intensive Care Unit (MICU) and are at high risk of additional infection. Further clinical development of SER-428 will be progressed pending funding from grants or other sources. The Company continues to advance IND-enabling activities for SER-603, in development for inflammatory bowel disease (IBD), and is engaging potential collaborators to support the clinical advancement of this program as a mono and/or combination therapy. Corporate Updates In October, Seres received the second of the two $12.5 million payments related to the buy-out of potential future VOWST net sales-based milestones from Nestlé Health Science (Nestlé). On July 31, Seres entered into an agreement to terminate the lease for its facility at 200 Sidney Street in Cambridge, MA. The early termination materially eliminates the Company's obligations under the lease as of December 31, 2026, and results in reduced ongoing facility-related cash costs beginning in 2027. Third Quarter 2026 Financial Results Net loss was $16.3 million for the third quarter of 2026, compared to net income of $8.2 million for the same period in 2025. The difference is primarily due to a $25 million installment payment received in the third quarter of 2025 related to the sale of the VOWST business to Nestlé, recognized as a Gain on Sale. Research and development expenses were $5.6 million for the third quarter of 2026, compared with $12.6 million for the same period in 2025, reflecting lower facilities costs, transition services agreement (TSA) costs, personnel-related expenses and SER-155 costs driven by lower activities in these areas and cost reduction efforts. General and administrative expenses were $5.4 million for the third quarter of 2026, compared with $9.5 million for the same period in 2025, due to lower personnel-related expenses, facilities costs, and IT costs, including those related to IT services provided under the TSA. In the third quarter of 2026, the Company recorded a $5.7 million non-cash impairment of assets charge related to the early termination of its lease at 200 Sidney Street. Cash and Cash Runway As of September 30, 2026, Seres had $17.5 million in cash and cash equivalents. Based on Seres' currently available cash resources, including the $12.5 million payment received from Nestlé in October, and considering future operating plans, the Company expects to fund operations through the first quarter of 2027. This projection excludes proceeds from any potential future partnerships or other sources of capital. About Seres Therapeutics Seres Therapeutics, Inc. (Nasdaq: MCRB) is a clinical-stage biotechnology company developing novel live biotherapeutics products in oncology that address causes of mortality and discontinuation of life-saving cancer treatment, and in inflammatory and immune (I&I) diseases, by modulating host function to protect and improve mucosal epithelial barrier integrity, induce immune homeostasis and tolerance, and prevent the colonization and overgrowth of pathogens in the gastrointestinal (GI) tract. The Company previously led the development and FDA approval of VOWST™, the first orally administered microbiome therapeutic, which was subsequently divested to Nestlé Health Science. SER-155, an investigational cultivated multi-strain biotherapeutic, which has received Breakthrough Therapy and Fast Track designations, is being advanced for the prevention of bloodstream infections in patients undergoing allogeneic hematopoietic stem cell transplant (allo-HCT), and is Phase 2 ready, pending receipt of funding. SER-155 is also being developed to prevent immune checkpoint inhibitor-related enterocolitis (irEC), with the aim of enabling patients to continue their ICI cancer therapy and avoid the need for immunosuppressive steroid treatment. Following promising results from an investigator-sponsored trial, Seres plans to submit the design of a study for the prevention of irEC in patients initiating ICI therapy to the FDA. The Company is advancing IND-enabling studies for SER-603, which is in development for inflammatory bowel disease. Mechanistically, Seres' biotherapeutics target the mucosal epithelial barrier-immune interface and are optimized to modulate host function to increase mucosal epithelium integrity, induce immune homeostasis, and prevent the colonization and overgrowth of harmful bacteria in the GI tract. For more information, please visit Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, without limitation, statements about: SER-155 and its intended uses and benefits in irEC; our clinical development plans for SER-155, SER-603 and SER-428, including the design and timing of the next planned study of SER-155 for the prevention of irEC; potential accessibility for patients; planned submissions to and/or engagement with regulatory authorities, including the anticipated timing of FDA feedback; the timing and results of clinical studies and data readouts; the anticipated content and timing of upcoming presentations and conferences; current or future product candidates and their potential impacts and outcomes; the size of potential patient populations and markets and the potential commercial opportunity for SER-155; engagement with potential partners and financing sources; our ability to access capital to advance our programs; IND-enabling activities; our cash runway; the anticipated effects of our lease termination, including expected reductions in facility-related costs; our planned strategic focus; the anticipated timing of any of the foregoing; and other statements that are not historical fact. These forward-looking statements are based on management's current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: (1) our need for additional funding; (2) our ability to continue as a going concern; (3) we have incurred significant losses, are not currently profitable and may never become profitable; (4) our cost reduction actions may not achieve their intended benefits, including an extended cash runway; (5) our limited operating history; (6) we may not be able to realize the anticipated benefits of the VOWST sale, and may face new challenges as a smaller, less diversified company; (7) we have in the past and may in the future receive notice of the failure to satisfy a continued listing rule from The Nasdaq Stock Market LLC; (8) our novel approach to therapeutic intervention; (9) our reliance on third parties to conduct our clinical trials and manufacture our product candidates; (10) our ability to achieve market acceptance necessary for commercial success; (11) the competition we will face; (12) our ability to protect our intellectual property; (13) impact of our recent management transitions and appointments and our ability to retain key personnel; and (14) disruptions at the FDA or other government agencies. These and other important factors discussed under the caption "Risk Factors" in our Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2026, to be filed with the Securities and Exchange Commission (SEC), as well as our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, except as required by law, we disclaim any obligation to do so, even if subsequent events cause our views to change. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. SERES THERAPEUTICS, INC. CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited, in thousands, except share and per share data) September 30, December 31, 2026 2025 Assets Current assets: Cash and cash equivalents $ 17,528 $ 45,766 Accounts receivable due from SPN - related party 12,500 360 Accounts receivable 183 157 Prepaid expenses and other current assets 4,212 3,093 Total current assets 34,423 49,376 Property and equipment, net 2,999 7,635 Operating lease assets 27,662 72,483 Restricted cash 773 8,668 Other non-current assets 31 31 Total assets $ 65,888 $ 138,193 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $ 1,461 $ 1,682 Accrued expenses and other current liabilities 3,504 3,972 Accrued liabilities due to SPN - related party 3,278 3,278 Operating lease liabilities 12,650 10,390 Total current liabilities 20,893 19,322 Operating lease liabilities, net of current portion 23,122 72,576 Other long-term liabilities 514 2,077 Total liabilities 44,529 93,975 Commitments and contingencies (Note 9) Stockholders’ equity: Preferred stock, $0.001 par value; 10,000,000 shares authorized at September 30, 2026 and December 31, 2025; no shares issued and outstanding at September 30, 2026 and December 31, 2025 — — Common stock, $0.001 par value; 360,000,000 shares authorized at September 30, 2026 and December 31, 2025; 10,049,501 and 9,556,466 shares issued and outstanding at September 30, 2026 and December 31, 2025, respectively 10 10 Additional paid-in capital 1,025,370 1,016,611 Accumulated deficit (1,004,021 ) (972,403 ) Total stockholders’ equity 21,359 44,218 Total liabilities and stockholders’ equity $ 65,888 $ 138,193 SERES THERAPEUTICS, INC. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE (LOSS) INCOME (unaudited, in thousands, except share and per share data) Three Months Ended September 30, Nine Months Ended September 30, 2026 2025 2026 2025 Revenue: Grant revenue 593 351 1,687 351 Total revenue 593 351 1,687 351 Operating expenses: Research and development expenses 5,592 12,616 27,928 37,376 General and administrative expenses 5,448 9,476 20,579 31,617 Impairment of long-lived assets 5,705 — 11,512 — Manufacturing services — 736 — 5,952 Total operating expenses 16,745 22,828 60,019 74,945 Loss from operations (16,152 ) (22,477 ) (58,332 ) (74,594 ) Other income (expense): Gain on sale of VOWST Business — 27,222 25,000 79,588 Interest income 146 618 652 1,782 Other income (expense) (1) (280 ) 2,841 1,062 14,255 Total other income (expense), net (134 ) 30,681 26,714 95,625 Net (loss) income and comprehensive (loss) income $ (16,286 ) $ 8,204 $ (31,618 ) $ 21,031 Net (loss) income per share attributable to common stockholders - basic $ (1.63 ) $ 0.94 $ (3.24 ) $ 2.41 Net (loss) income per share attributable to common stockholders - diluted $ (1.63 ) $ 0.94 $ (3.24 ) $ 2.40 Weighted average common shares outstanding - basic 9,982,031 8,758,692 9,764,763 8,735,418 Weighted average common shares outstanding - diluted 9,982,031 8,771,519 9,764,763 8,744,797 [1] Includes $0, $0, $2,028, and $11,827 for the three and nine months ended September 30, 2026 and 2025 related to reimbursement received from SPN (related party) for transition services provided by the Company. Investor and Media Contact: IR@serestherapeutics.com Carlo Tanzi, Ph.D. Kendall Investor Relations ctanzi@kendallir.com

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KEGG	Wiki	ATC	Drug Bank
D10808	度伐利尤单抗	L01FF03	DB11714

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适应症	国家/地区	公司	日期
非肌层浸润性膀胱肿瘤	美国	AstraZeneca UK Ltd.	2026-05-28
胃癌	欧盟	AstraZeneca AB	2026-03-16
胃癌	冰岛	AstraZeneca AB	2026-03-16
胃癌	列支敦士登	AstraZeneca AB	2026-03-16
胃癌	挪威	AstraZeneca AB	2026-03-16
早期胃癌	美国	AstraZeneca PLC	2025-11-25
胃食管交界处腺癌	美国	AstraZeneca UK Ltd.	2025-11-25
胃食管交界处癌	美国	AstraZeneca PLC	2025-11-25
局部晚期胃癌	美国	AstraZeneca PLC	2025-11-25
不可切除的非小细胞肺癌	中国	AstraZeneca UK Ltd.	2025-11-18
肌层浸润性膀胱癌	美国	AstraZeneca UK Ltd.	2025-03-28
子宫癌	日本	阿斯利康制药有限公司	2024-11-22
晚期子宫内膜癌	欧盟	AstraZeneca AB	2024-08-15
晚期子宫内膜癌	冰岛	AstraZeneca AB	2024-08-15
晚期子宫内膜癌	列支敦士登	AstraZeneca AB	2024-08-15
晚期子宫内膜癌	挪威	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	欧盟	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	冰岛	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	列支敦士登	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	挪威	AstraZeneca AB	2024-08-15

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适应症	最高研发状态	国家/地区	公司	日期
ALK阳性非小细胞肺癌	申请上市	中国	AstraZeneca AB	2025-02-21
EGFR突变的非小细胞肺癌	申请上市	中国	AstraZeneca UK Ltd.	2025-02-21
卵巢上皮癌	申请上市	中国	AstraZeneca UK Ltd.	2024-08-16
微卫星稳定型实体瘤	临床3期	西班牙	AstraZeneca PLC	2024-12-30
晚期神经内分泌癌	临床3期	日本	AstraZeneca KK	2023-12-01
胃肠胰神经内分泌肿瘤	临床3期	日本	AstraZeneca KK	2023-12-01
小细胞癌	临床3期	日本	AstraZeneca KK	2023-12-01
PD-L1阳性三阴性乳腺癌	临床3期	美国	AstraZeneca PLC	2023-11-23
PD-L1阳性三阴性乳腺癌	临床3期	中国	AstraZeneca PLC	2023-11-23
PD-L1阳性三阴性乳腺癌	临床3期	日本	AstraZeneca PLC	2023-11-23

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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


AASLD2026	N/A	不可切除的肝细胞癌一线	90	Tremelimumab plus durvalumab	艱範憲築製壓窪範製廠(獵獵鹽範願築願鏇積襯) = 獵繭蓋鹹觸顧鑰醖憲遞鹹蓋鏇簾製鬱艱繭築膚 (廠齋製齋窪餘廠簾廠鬱, 1.5 ~ 5.9) 更多	积极	2026-11-05
				Tremelimumab plus durvalumab (patients with Vp4 PVTT)	淵壓範築衊範範觸蓋選(窪簾襯鬱膚蓋顧鏇齋獵) = 艱鑰齋網蓋淵壓鹹製製憲夢鏇窪製襯簾選艱製 (鬱鹹顧獵鬱鑰鹹齋餘簾 ) 更多
AASLD2026	临床2/3期	晚期胆道癌一线	3,000	Durvalumab + Gemcitabine + Cisplatin	鹹齋選窪襯選夢衊鏇廠(顧構範鑰艱壓顧齋窪遞): HR = 0.74 (95.0% CI, 0.63 ~ 0.87)	积极	2026-11-05
				Pembrolizumab + Gemcitabine + Cisplatin
AASLD2026	N/A	不可切除的肝内胆管癌 TP53 mutations	41	gemcitabine, cisplatin, and durvalumab (GCD) or gemcitabine, cisplatin, and pembrolizumab (GCP)	衊觸廠網顧壓鹹鹽積簾(壓衊獵齋網蓋簾鹽獵膚) = 顧壓襯構顧獵衊範鬱廠衊憲夢齋構觸製壓鹽範 (選蓋獵壓鹹餘襯鹽構範, 4.4 ~ 10.7) 更多	积极	2026-11-05
				gemcitabine, cisplatin, and durvalumab (GCD) or gemcitabine, cisplatin, and pembrolizumab (GCP) (TP53 wild-type ICC)	衊觸廠網顧壓鹹鹽積簾(鬱積選網醖鏇顧衊膚築) = 鏇築簾網繭憲鏇壓範鬱衊構齋遞壓餘遞鑰顧鏇 (齋蓋網窪醖積選襯襯淵, 4.4 ~ 10.7) 更多
AASLD2026	N/A	肝细胞癌一线	1,487	Durvalumab-based regimens	構窪繭糧膚願觸壓繭觸(壓願鬱壓窪窪獵鏇積醖) = 衊鹹夢願鏇簾選廠構鹹糧齋鹽鹹簾簾蓋廠膚蓋 (遞築餘網製憲選襯衊積 ) 更多	积极	2026-11-05
				atezolizumab+bevacizumab	鑰壓鬱鏇廠憲鹹觸鏇餘(簾獵構醖憲夢窪蓋願廠) = 齋獵範顧遞獵鹽顧廠夢顧蓋獵憲膚鏇餘鑰淵鬱 (窪繭鏇壓餘窪鑰顧顧淵 )
ESMO2026	N/A	胆道癌一线	34	Durvalumab plus gemcitabine/platinum	齋齋糧選艱廠鏇鑰壓繭(製齋製願衊膚積醖構積) = 鏇淵壓鬱網齋積壓齋鏇艱簾遞膚願齋遞築選願 (鑰構鹹網簾壓淵壓窪膚 ) 更多	积极	2026-10-23
ESMO2026	N/A	广泛期小细胞肺癌一线	285	platinum-etoposide plus atezolizumab or durvalumab	積憲顧構廠醖糧餘鬱選(築範選鹽網壓選齋廠糧) = 願夢願齋繭築夢衊獵構鹹鏇艱鏇齋築齋餘觸憲 (築憲糧鏇夢築繭積遞選, 8.4 ~ 10.8) 更多	不佳	2026-10-23
NCT05061550 (NeoCOAST-2, ESMO2026)	临床2期	非小细胞肺癌新辅助	202	Durvalumab + Oleclumab + Platinum	網廠鏇簾艱顧構蓋顧選(齋廠遞積繭觸築齋繭鏇) = 觸製夢壓願夢糧艱構鏇鹹蓋網襯蓋顧範構顧網 (網積窪網壓蓋膚壓願鹽 ) 更多	积极	2026-10-23
				Durvalumab + Monalizumab + Platinum	網廠鏇簾艱顧構蓋顧選(齋廠遞積繭觸築齋繭鏇) = 糧製製糧衊鏇遞顧憲願鹹蓋網襯蓋顧範構顧網 (網積窪網壓蓋膚壓願鹽 ) 更多
NCT03704480 (IMMUNO-BIL, ESMO2026)	临床2期	胆道癌二线	80	durvalumab + tremelimumab	鏇齋壓鹹鏇廠選構顧齋(醖膚鹽製蓋襯網衊製網) = 繭製蓋夢製積窪製艱鹽鏇鹹衊簾蓋鬱夢膚遞壓 (鹽製衊選範顧壓夢願衊 ) 更多	积极	2026-10-23
NCT04392505 (DART, ESMO2026)	临床2期	非小细胞肺癌 III期 ctDNA	84	durvalumab+chemoradiotherapy	顧鏇觸構獵觸膚齋憲蓋(壓構憲襯繭獵淵衊齋蓋): HR = 12.2 (95.0% CI, 3.5 ~ 42.5), P-Value = < 0.0001 更多	积极	2026-10-23
				durvalumab+chemoradiotherapy (ctDNA detected in at least two consecutive surveillance samples)
ESMO2026	N/A	胆道癌新辅助	89	gemcitabine/cisplatin	鹽製範衊衊繭廠艱夢鹹(鹽願範鬱窪鹽構壓衊齋) = 築積膚餘夢齋獵廠憲鏇網獵繭構齋憲淵繭顧齋 (網襯遞艱鏇夢醖網蓋鬱 ) 更多	积极	2026-10-23