A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Combined With Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer

This phase I/II trial tests the safety, side effects, and best dose of iadademstat when given together with atezolizumab or durvalumab, and studies the effect of the combination in treating patients with small cell lung cancer that has spread outside of the lung in which it began or to other parts of the body (extensive stage) who initially received standard of care chemotherapy and immunotherapy. Iadademstat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab or durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding iadademstat to either atezolizumab or durvalumab may be able to stabilize cancer for longer than atezolizumab or durvalumab alone in treating patients with extensive stage small cell lung cancer.

开始日期2025-08-17

申办/合作机构

National Cancer Institute

NCT06732401 / Not yet recruiting临床3期IIT

A Randomized Phase III Trial of Checkpoint Blockade in Lung Cancer Patients in the Adjuvant Setting Based on Pathologic Response Following Neoadjuvant Therapy (CLEAR)

This phase III trial compares the effect of adding AZD6738 to durvalumab versus durvalumab alone to increase time without cancer in patients with non-small cell lung cancer, following treatment with chemotherapy and surgery. AZD6738 may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Adding AZD6738 to durvalumab may increase time without cancer in patients with non-small cell lung cancer, following treatment with chemotherapy and surgery.

开始日期2025-03-14

申办/合作机构

National Cancer Institute

NCT06692491 / Not yet recruiting临床2期IIT

A Phase II Clinical Study on Precision Treatment of Rare Tumours in China Guided by Patient-Derived Tumor Organoids (PDO) and Next-Generation Sequencing (NGS)

The objective of this Phase II, open-label, multicenter, non-randomised controlled clinical trial is to guide precision treatment for patients with rare tumours based on Patient-Derived Organoids/Next-Generation Sequencing drug screening.

开始日期2025-01-01

申办/合作机构

北京大学深圳医院（北京大学深圳临床医学院）

100 项与 Dulaglutide 相关的临床结果

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100 项与 Dulaglutide 相关的转化医学

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100 项与 Dulaglutide 相关的专利（医药）

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787

项与 Dulaglutide 相关的文献（医药）

2025-01-01·Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

Safety and Efficacy of Efruxifermin in Combination With a GLP-1 Receptor Agonist in Patients With NASH/MASH and Type 2 Diabetes in a Randomized Phase 2 Study

Article

作者: Reiss, Gary ; Bollepalli, Sureka ; Shringarpure, Reshma ; Frias, Juan P ; Tillman, Erik J ; de Temple, Brittany ; Harrison, Stephen A ; Zari, Arian ; Rolph, Timothy ; Cheng, Andrew ; Moulton, Ali ; Chan, Doreen ; Neff, Guy ; Su, Yan ; Lucas, K Jean ; Yale, Kitty

BACKGROUND & AIMS:

In phase 2 studies, efruxifermin, an Fc-FGF21 analog, significantly reduced steatohepatitis and fibrosis in patients with non-alcoholic steatohepatitis, now called metabolic dysfunction-associated steatohepatitis (MASH), for which there is no approved treatment. Type 2 diabetes (T2D) and obesity are prevalent among patients with MASH and increasingly treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). This study evaluated the safety and efficacy of efruxifermin in patients with MASH, fibrosis, and T2D taking a GLP-1RA.

METHODS:

Cohort D was a double-blind, placebo-controlled, phase 2b study in adults with T2D and MASH with fibrosis (F1-F3) on stable GLP-1RA therapy randomized (2:1) to receive efruxifermin 50 mg or placebo, once weekly for 12 weeks. The primary endpoint was safety and tolerability of efruxifermin added to a stable dose of GLP-1RA. Secondary endpoints included changes in hepatic fat fraction (HFF), markers of liver injury and fibrosis, and metabolic parameters.

RESULTS:

Adults (N = 31) with T2D and MASH fibrosis (F1-F3) on a stable GLP-1RA (semaglutide, 48.4%; dulaglutide, 45.2%; liraglutide, 6.5%) received efruxifermin 50 mg (n = 21) or placebo (n = 10) for 12 weeks. The addition of efruxifermin to a GLP-1RA appeared safe and well-tolerated. The most frequent efruxifermin-related adverse events were mild to moderate gastrointestinal events. One patient receiving efruxifermin discontinued due to nausea, and another withdrew consent. There were no treatment-related serious adverse events. After 12 weeks, efruxifermin reduced HFF by 65% (P < .0001 vs placebo) compared with a 10% reduction for placebo (GLP-1RA alone). Efruxifermin also improved noninvasive markers of liver injury, fibrosis, glucose, and lipid metabolism while maintaining GLP-1RA-mediated weight loss.

CONCLUSIONS:

The tolerability profile of efruxifermin added to GLP-1RA appeared comparable to that of either drug alone, while also significantly reducing HFF and noninvasive markers of fibrosis in patients with MASH and T2D. Liver health in patients already on a GLP-1RA may be further improved by addition of efruxifermin.

CLINICALTRIALS:

gov, Number: NCT05039450.

2025-01-01·JOURNAL OF AFFECTIVE DISORDERS

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: A replication study using reports to the World Health Organization pharmacovigilance database (VigiBase®)

Article

作者: Le, Gia Han ; Mansur, Rodrigo B. ; Rhee, Taeho Greg ; Rosenblat, Joshua D. ; McIntyre, Roger S ; Ho, Roger ; McIntyre, Roger S. ; Kwan, Angela T.H. ; Rosenblat, Joshua D ; Teopiz, Kayla M ; Wong, Sabrina ; Kwan, Angela T H ; Cao, Bing ; Teopiz, Kayla ; Mansur, Rodrigo B

INTRODUCTION:

Reports of suicidality associated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been reported to the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA). We previously reported an increased reporting odds ratio (ROR) of some measures of suicidality with semaglutide and liraglutide using the FDA Adverse Event Reporting System (FAERS). Notwithstanding the increased ROR, causality between GLP-1 RAs exposure and any aspect of suicidality is not established.

RESEARCH DESIGN AND METHODS:

The analysis herein aims to extend a previous analysis of the FAERS by evaluating the ROR for suicidality reported to the World Health Organization (WHO) Pharmacovigilance Database (VigiBase). We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports. As per our previous report, the ROR was considered significant when the lower limit of the 95 % confidence (CI) was >1.0.

RESULTS:

We searched VigiBase reports from inception to January 2024. The RORs for suicidal ideation were significantly increased for semaglutide (5.82), liraglutide (4.03) and tirzepatide (2.25). For "depression/suicidal", the ROR was significantly increased for semaglutide (14.74) and liraglutide (5.86); and for suicidal behaviour, the ROR was significantly increased for semaglutide (6.52) and liraglutide (3.90). However, for suicide attempts, the ROR was significantly decreased for semaglutide (0.11), dulaglutide (0.075), exenatide (0.047) and liraglutide (0.15). For completed suicide, the ROR was also significantly decreased for semaglutide (0.01), dulaglutide (0.003), exenatide (0.002) and liraglutide (0.008).

CONCLUSION:

Unlike our previous report with FAERS, a mixed pattern of ROR emerged in the WHO VigiBase with respect to suicidality and exposure to select GLP-RAs. Causation between GLP-1 RA exposure and suicidality (either increased or decreased) cannot be ascertained from ROR data.

2025-01-01·ANNALS OF PLASTIC SURGERY

Glucagon-Like Peptide-1 Agonists

Review

作者: Daar, David A. ; Hong, Kurt ; Koesters, Emma ; Manasyan, Artur ; Stanton, Eloise W. ; Banerjee, Rakhi

Background:

Glucagon-like peptide-1 (GLP-1) agonists, such as exenatide, liraglutide, dulaglutide, semaglutide, and tirzepatide, effectively manage type 2 diabetes by promoting insulin release, suppressing glucagon secretion, and enhancing glucose metabolism. They also aid weight reduction and cardiovascular health, potentially broadening their therapeutic scope. In plastic surgery, they hold promise for perioperative weight management and glycemic control, potentially impacting surgical outcomes.

Methods:

A comprehensive review was conducted to assess GLP-1 agonists' utilization in plastic surgery. We analyzed relevant studies, meta-analyses, and trials to evaluate their benefits and limitations across surgical contexts, focusing on weight reduction, glycemic control, cardiovascular risk factors, and potential complications.

Results:

Studies demonstrate GLP-1 agonists' versatility, spanning weight management, cardiovascular health, neurological disorders, and metabolic dysfunction-associated liver diseases. Comparative analyses highlight variations in glycemic control, weight loss, and cardiometabolic risk. Meta-analyses reveal significant reductions in hemoglobin A1C levels, especially with high-dose semaglutide (2 mg) and tirzepatide (15 mg). However, increased dosing may lead to gastrointestinal side effects and serious complications like pancreatitis and bowel obstruction. Notably, GLP-1 agonists' efficacy in weight reduction and glycemic control may impact perioperative management in plastic surgery, potentially expanding surgical candidacy for procedures like autologous flap-based breast reconstruction and influencing outcomes related to lymphedema. Concerns persist regarding venous thromboembolism and delayed gastric emptying, necessitating further investigation into bleeding and aspiration risk with anesthesia.

Conclusions:

GLP-1 agonists offer advantages in perioperative weight management and glycemic control in plastic surgery patients. They may broaden surgical candidacy and mitigate lymphedema risk but require careful consideration of complications, particularly perioperative aspiration risk. Future research should focus on their specific impacts on surgical outcomes to optimize their integration into perioperative protocols effectively. Despite challenges, GLP-1 agonists promise to enhance surgical outcomes and patient care in plastic surgery.

993

项与 Dulaglutide 相关的新闻（医药）

2024-12-24

·Antibody Research

创响生物与Ikena Oncology合并，融资7500万美元，OX40 单克隆抗体能否撑起未来？

▎追溯 2024 年 12 月 23 日（GLOBE NEWSWIRE）——Ikena Oncology, Inc.（纳斯达克股票代码：IKNA，“Ikena”）和 Inmagene Biopharmaceuticals（“Inmagene”、“创响生物”）宣布双方已达成最终合并协议。在此次合并中，Ikena 已与 Deep Track Capital、Foresite Capital、RTW Investments 等新投资者达成认购协议，以认购 7500 万美元的私募（“融资”），除此之外还包括BVF Partners LP、Blue Owl Healthcare Opportunities、Omega Funds 和 OrbiMed 等现有 Ikena 投资者。合并后的公司将专注于开发针对 OX40 的单克隆抗体 (mAb) IMG-007，用于治疗特应性皮炎。合并后的公司计划以“ImageneBio, Inc.”的名义运营。（“ImageneBio”）并在纳斯达克以股票代码“IMA”进行交易。早在去年创响发布了部分内容。介绍OX40与OX40配体的相互作用在T细胞介导的疾病的发病机制中发挥重要作用。OX40拮抗剂已在特应性皮炎（AD）中展示了临床疗效。然而，具有增强抗体依赖细胞介导的细胞毒性（ADCC）功能的OX40单克隆抗体报告了输注或注射相关反应。IMG-007是一种具有Fc调节功能并沉默ADCC的OX40抗体，旨在最小化潜在的安全风险。方法本研究是一项1期、双盲、随机、安慰剂对照、单次递增剂量的研究，旨在评估IMG-007在健康成人参与者中的安全性和药代动力学（PK）特征。结果共有44名参与者接受了IMG-007或安慰剂治疗（30:14）。评估了七个剂量队列（1 mg至600 mg），并进行了12或16周的随访。IMG-007耐受良好，没有出现严重或重度的不良事件（AE），也没有出现任何提示局部或全身输注相关反应的AE，如发热或寒战。安全性实验室参数未出现临床显著变化。最常见的不良事件（44名参与者中9例）是接触性皮炎，主要发生在静脉插管或心电图电极贴片的部位。中期药代动力学分析显示，IMG-007呈现经典的靶介导药物分布（TMDD）动力学，药代动力学表现为剂量依赖性，剂量范围为30 mg至600 mg，且在该剂量范围内的平均终末半衰期为12.9天至37.9天。结论单次剂量高达600 mg的IMG-007在健康参与者中耐受良好，并在高剂量下表现出延长的半衰期。IMG-007代表了一种治疗AD及其他T细胞介导的疾病的独特治疗候选药物。值得一提的是IMG-007并没有出现发热和寒战等副作用。IMG-007，作为一种非消耗性抗 OX40 单克隆抗体，通过抗体工程设计延长了半衰期，同时沉默了ADCC功能，与协和麒麟的Rocatinlimab（KHK4083）设计正好相反。 OX40/OX40L在自免领域一直有人尝试，但是开发OX40好，还是OX40L的好，一直没有定论，直到这两者的临床数据披露。 Rocatinlimab（KHK4083）是协和发酵麒麟研发的抗OX40全人源单抗，是一款具有ADCC作用的阻断型OX40抗体。但其副作用明显，与安慰剂相比，在第16周时，所有rocatinlimab的EASI评分均出现显著的最小二乘平均百分比下降。在双盲期内，接受rocatinlimab治疗的患者中最常见的不良事件是发热（36[17%]）、鼻咽炎（30[14%]），寒战（24[11%]人员），头痛（19[9%]），溃疡（15[7%]）和恶心（13[6%]），未发生患者死亡。可以看出接受Rocatinlimab（KHK4083）治疗的患者中有一部分发生了发热等副作用，在一定程度上可以说明，OX40抗体，还是有一定的系统性激活作用。因为其作用机制中存在这样的隐患，虽然其增强了ADCC，想要去消耗T细胞，但是也同样给OX40提供了一定交联信号，使得T细胞在一定程度上得到激活，从而引发发热，寒战，炎症等副作用。而IMG-007因为沉默了Fc作用，所以在一定程度上潜在的没有了交联作用。但在我开发激动剂的过程中发现，OX40，41BB，CD40等一类抗体，大多数或多或少其实仍会有一定的激活作用，在交联的情况下，激活明显提升。当然也存在一定激活背景相对干净的，同时IMG-007也做了Fc处理，具体还要等后续IMG-007更多数据的公布。目前来看有潜在优于Rocatinlimab（KHK4083）。 Rocatinlimab（KHK4083）在2b期、随机、双盲、安慰剂对照研究中（NCT03703102），274例中重度AD成人患者被随机分配（1:1:1:1:1）接受rocatinlimab 150 mg Q4W、600 mg Q4W、300 mg Q2W、600 mg Q2W或安慰剂皮下注射治疗。结果显示，在第16周，与安慰剂组相比，所有rocatinlimab组的EASI评分较基线的平均百分比变化均显著降低（-48.3%至-61.1%）; p均<0.001），并且停药20周后仍能维持临床疗效。数据一般。2024年9月25日，安进公布自免/炎症领域最新临床进展，包括OX40抗体Rocatinlimab治疗特应性皮炎的三期临床前线数据。HORIZON研究达到主要终点，Rocatinlimab和安慰剂组的EASI-75响应率分别为32.8%和13.7%，Rocatinlimab和安慰剂组的vIGA-AD 0/1的响应率为19.3%和6.6%。仍不亮眼。而我们再来看赛诺菲的一款OX40L抗体，amlitelimab，的副作用，amlitelimab治疗中出现的不良事件(TEAE)的总体发生率为67.4%，安慰剂组为60.3%。与安慰剂相比，Amlitelimab更常见的TEAE包括鼻咽炎（11.0% vs 9.0%）、COVID-19（7.7% vs 6.4%）和头痛（6.1% vs 2.6%）。与Amlitelimab相比，安慰剂组更常见特应性皮炎恶化（38.5% vs 17.1%）。未观察到不良事件如发烧或发冷、口腔溃疡或结膜炎等。 OX40L抗体amlitelimab并不会出现系统性激活T细胞的副作用，整体安全性跟安慰剂相当。要远远优于OX40抗体Rocatinlimab。从疗效方面，也是OX40L抗体amlitelimab更优。副作用也更小。在500mg(LD)后再接受每4周1次250mg剂量组患者缓解程度最高，第16周时EASI较基线降低了61.5%（P<0.0001），24周时降低了64.4%（P<0.0001），而安慰剂组分别为29.4%和27.6%。 IGA 0/1评分中，治疗组 22.1% 和 45.5%患者在第16周和第24周达到 IGA 0/1（完全清除/基本清除），而安慰剂组患者对应的这一比例为5.1%和11.4%（P=0.0022和P<0.0001）。关于EASI-75评分，在接受相同剂量治疗的患者中，治疗组分别有40.3%和54.5% 患者在第16周和第24周达到EASI-75，而安慰剂组的这一比例为11.4%和17.7%（均P<0.0001）。整体数据跟dupilumab（IL-4Rα抗体）相当。 OX40–OX40L作为T细胞二级共刺激信号，两者相互作用在AD（特应性皮炎）的发病机制中发挥着核心影响力，相关联Th1/Th2/Th17/Th22通路，OX40L抑制剂一定程度上可以解决瘙痒问题。而其它治疗方式在治疗瘙痒方面略差。创响生物主要布局自免领域。关于拟议交易和合并后公司管理合并和融资完成后，Ikena 股东预计将持有合并后公司约 34.8% 的股份，Inmagene 股东预计将持有约 43.5% 的股份，融资投资者预计将持有约 21.7% 的股份。合并后公司的董事会将由来自当前 Inmagene 董事会的三名董事、来自当前 Ikena 董事会的两名董事、一名代表融资投资者的董事会成员和一名新的独立董事会成员组成。Inmagene 和 Ikena 将共同决定 ImageneBio 的未来领导层，并已开始正式寻找合并后公司的首席执行官。两家公司的股东将获得或有价值权 (CVR)。Inmagene 股东将获得 Inmagene 非 IMG-007 资产的或有价值权，而 Ikena 股东将获得 Ikena 原有管道资产的或有价值权。该交易已获得两家公司董事会的批准，预计将于 2025 年中期完成，但须满足惯例成交条件，包括获得各自公司股东的批准。就此次反向合并而言，两家公司的董事和高管、Inmagene 的某些股东以及 Ikena 的某些股东已签署了支持协议，根据协议条款，他们同意投票支持此次合并或在合并中发行 Ikena 股票（如适用）。欢迎加入我的知识星球，可提供专业的免费咨询。公众号已经建立读者实名讨论微信群，可以添加微信（zhuisu2210）后进群，添加时请主动注明姓名、企业、职位。

临床1期抗体药物偶联物

2024-12-23

·GlobeNewswire-Health Care

CORXEL Acquires Worldwide (excluding Greater China) Rights to an Oral Small Molecule GLP-1 RA for the Treatment of Obesity and Diabetes

CORXEL expands its cardiometabolic pipeline into obesity and diabetesNEW JERSEY and SHANGHAI, Dec. 23, 2024 (GLOBE NEWSWIRE) -- Corxel Pharmaceuticals (CORXEL), a leading biotech company committed to bringing innovative science and medicines to underserved patients with cardiometabolic diseases around the world, today announced the acquisition of CX11 (also known as VCT220), an oral small molecule glucagon-like peptide-1 receptor agonist (GLP-1 RA), for worldwide (excluding Greater China) development and commercialization, from Vincentage. CX11 is an investigational, oral small molecule GLP-1 RA for the treatment of cardiometabolic diseases, including obesity and type 2 diabetes. GLP-1 RAs have been shown to lower bodyweight, improve insulin sensitivity, and reduce glucose and overall appetite. CX11, in a once daily orally available formulation, could offer convenience and accessibility to patients, and lower the cost of manufacturing compared to injectables. In a Phase 2 clinical trial conducted in China, CX11 demonstrated competitive weight loss with favorable safety and tolerability. The registrational Phase 3 study in obese and overweight patients in China has been initiated in November 2024. CORXEL plans to initiate a global (excluding Greater China) Phase 2 study in obese and overweight patients in 2025. “Obesity has become a major risk factor for a number of chronic diseases like diabetes, hypertension, liver disease, and also including cardiovascular diseases such as heart disease and stroke, which are the leading causes of death worldwide. This acquisition marks CORXEL’s expansion of its cardiometabolic pipeline into obesity and diabetes, and we are excited about the potential of CX11, which has shown impressive efficacy in weight reduction, making it a potential best-in-class oral small molecule GLP-1 RA,” said Sandy Mou, Board Executive Director and Chief Executive Officer of CORXEL. “Since its establishment, CORXEL has proven its strong capabilities in asset selection, clinical development, registration and partnering in manufacturing for innovative medicines. Our global team is fully committed to developing CX11 with high quality and efficiency, allowing CORXEL to tap into the tremendous obesity market worldwide.” “We are very delighted that CORXEL will be advancing the global development of VCT220 (CX11). CORXEL has strong clinical development capabilities and global promotional strengths. We look forward to CORXEL accelerating the clinical trials and bringing this innovative oral GLP-1 molecule to patients worldwide in the future,” said Ben Li, Chief Executive Officer of Vincentage. About CORXEL CORXEL is a leading biotech company headquartered in US and China focused on developing innovative cardiometabolic therapies globally. CORXEL was founded in 2019 and has been committed to bringing innovative science and medicines to underserved patients around the world. With a strong and further developing asset pipeline, industry leading talent, and patient-centric focus, CORXEL is dedicated to delivering a meaningful and lasting impact on patients.  The portfolio of CORXEL consists of 3 assets with global rights and 2 assets with Greater China rights in late-stage clinical development. The portfolio with global rights covers CX11 for obesity and diabetes, JX10 for acute ischemic stroke (AIS) and JX09 for hypertension, while the portfolio with Greater China rights includes Etripamil and LNZ100. For further information about CORXEL, please visit www.corxelbio.com   Media contact: media@corxelbio.com About Vincentage Vincentage is a clinical-stage biotech, focusing on developing novel small molecule drugs for metabolic diseases. The company has developed small molecule innovative drugs targeting different mechanisms and targets for metabolic-related diseases, such as diabetes, obesity, and MASH.

临床2期并购

2024-12-23

·生物世界

Cell：空间组学揭示卵巢癌产生的IL-4促进免疫治疗耐药，并发现潜在治疗药物

撰文丨王聪编辑丨王多鱼排版丨水成文卵巢癌（Ovarian cancer）是最致命的癌症之一，50%的乳腺癌患者在确诊后5年内死亡。虽然靶向PD-1/PD-L1的免疫检查点阻断（ICB）疗法在包括黑色素瘤、肺癌在内的中显示出良好的效果，但对于卵巢癌，ICB疗法临床获益有限，客观缓解率不足10%。部分原因是卵巢肿瘤的基因突变较少，使得免疫系统更难识别它们。此外，研究显示，卵巢肿瘤可能通过制造屏障阻止免疫细胞浸润来抵抗免疫治疗。这也带来了一个关键问题——卵巢肿瘤是如何建立起这些自我保护性的环境的？近日，西奈山伊坎医学院的研究人员在国际顶尖学术期刊 Cell 上发表了题为：Ovarian cancer-derived IL-4 promotes immunotherapy resistance 的研究论文【1】。该研究利用空间功能基因组学筛选技术Perturb-map，发现卵巢癌细胞通过产生白细胞介素-4（IL-4）来创造一个保护性微环境，阻止免疫细胞的杀伤，使卵巢癌细胞对免疫治疗产生抵抗。该研究进一步证实，已获得FDA批准的IL-4阻断药物dupilumab（用于治疗哮喘和特应性皮炎）与抗PD-1单抗联用，可增强卵巢癌免疫治疗效果。早在2022年3月，该团队在 Cell 期刊发表论文【2】，开发了一种新型空间功能基因组学筛选技术——Perturb-map，Perturb-map通过结合最先进的空间成像技术，增强了传统的CRISPR基因筛选，同时“扰动”数百个基因，使得每个基因在控制肿瘤环境中的作用得以阐明。卵巢癌对免疫治疗产生抵抗，这受巨噬细胞主导的免疫抑制性的肿瘤微环境（TME）的影响，还受到肿瘤内异质性的影响，而肿瘤内异质性的发生机制尚不清楚。为了确定卵巢癌免疫调控因子，研究团队使用了Perturb-map技术，重点关注了可能参与肿瘤-巨噬细胞通讯的受体/配体。Perturb-map再现了卵巢肿瘤的异质性，并揭示了白细胞介素-4 （IL-4）促进了卵巢肿瘤对于抗PD-1的耐药性，从卵巢癌细胞中敲除IL-4可使肿瘤对于抗PD-1治疗敏感。该研究发现，卵巢癌细胞是IL-4的主要来源，IL-4通过巨噬细胞控制来指导免疫抑制性的肿瘤微环境（TME）的形成。该研究还发现，IL-4的缺失不能由附近的IL-4表达克隆来补偿，也就是说，缺乏IL-4的肿瘤细胞即使与表达IL-4的肿瘤细胞混合在一起，缺乏IL-4的肿瘤细胞仍会被免疫系统清除。进一步的临床前研究表明，卵巢癌使用IL-4将巨噬细胞编程为癌细胞的保护细胞。IL-4编程的巨噬细胞阻止了T细胞对癌细胞的杀伤。而当IL-4被阻断时，癌细胞周围的局部环境发生变化，这使得癌细胞变得容易被免疫系统清除。研究团队在侵袭性转移性卵巢癌小鼠模型中测试了抗PD-1单抗和IL-4受体阻断药物（dupilumab，一种IL-4Rα拮抗剂）的联合治疗，结果显示，这种联合治疗显著延长了小鼠的生存期。为了进一步验证这些发现，研究团队检查了人类卵巢肿瘤切除标本，发现人类卵巢癌患者的癌细胞同样产生了IL-4。此外，对来自卵巢癌患者肿瘤的单细胞RNA测序数据显示，巨噬细胞显示出强烈的IL-4特征，这表明了IL-4在人类卵巢癌中发挥着类似的作用，这可能是卵巢癌患者未能从免疫治疗中获益的原因之一。这些发现表明，肿瘤来源的细胞因子/趋化因子的局部表达改变可产生异质性的肿瘤微环境（TME），这些细胞因子/趋化因子建立了免疫富集和免疫排斥的区域，从而驱动克隆选择和免疫治疗耐药。同时，这些发现也证明了靶向IL-4信号通路增强卵巢癌对免疫治疗反应的潜力。卵巢癌是一种很难早期发现的癌症，一旦诊断出来，往往为时已晚。考虑到卵巢癌几乎对现有的所有免疫疗法都没有反应，而该研究发现，阻断IL-4能够改变卵巢肿瘤微环境，使这种难治性肿瘤变得更容易治疗，这对卵巢癌研究来说是一个重大突破。度普利尤单抗（dupilumab）已被美国FDA批准用于治疗哮喘和特应性皮炎，因此其可能与免疫疗法联合使用以提高卵巢癌患者的生存率。目前，研究团队已经在进行一项临床研究，以测试dupilumab是否可以改善肺癌患者的抗PD-1免疫治疗效果，其中一些患者已经显示出有益的反应。论文链接： 1. https://www.cell.com/cell/abstract/S0092-8674(24)01154-1 2. https://www.cell.com/cell/fulltext/S0092-8674(22)00195-7 设置星标，不错过精彩推文开放转载欢迎转发到朋友圈和微信群微信加群为促进前沿研究的传播和交流，我们组建了多个专业交流群，长按下方二维码，即可添加小编微信进群，由于申请人数较多，添加微信时请备注：学校/专业/姓名，如果是PI/教授，还请注明。点在看，传递你的品味

免疫疗法临床结果

100 项与 Dulaglutide 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09889	Dulaglutide	A10BJ05	DB09045

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
2型糖尿病	美国	Eli Lilly & Co.	2014-09-18

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
低血糖	临床3期	日本	Eli Lilly & Co.	2021-04-13
慢性肾病	临床3期	美国	Eli Lilly & Co.	2012-07-01
慢性肾病	临床3期	巴西	Eli Lilly & Co.	2012-07-01
慢性肾病	临床3期	匈牙利	Eli Lilly & Co.	2012-07-01
慢性肾病	临床3期	墨西哥	Eli Lilly & Co.	2012-07-01
慢性肾病	临床3期	波兰	Eli Lilly & Co.	2012-07-01
慢性肾病	临床3期	罗马尼亚	Eli Lilly & Co.	2012-07-01
慢性肾病	临床3期	南非	Eli Lilly & Co.	2012-07-01
慢性肾病	临床3期	西班牙	Eli Lilly & Co.	2012-07-01
慢性肾病	临床3期	乌克兰	Eli Lilly & Co.	2012-07-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ACAAI2024	N/A	Job综合征 \| 特应性皮炎 IgE levels	-	Dupilumab	醖淵獵網鏇憲艱憲淵糧(糧構築襯顧選簾鏇製鏇) = 憲窪餘鑰積壓積製糧製膚簾憲鹹鬱鬱觸憲壓夢 (齋窪憲製積齋製顧壓淵 )	积极	2024-10-24
ASTRO	N/A	放射性肺炎	-	Durvalumab	蓋範壓鏇遞窪簾餘簾網(願網齋蓋憲齋淵範糧襯) = Pneumonitis was recorded in 35 pts. (29.4%): G1-12; G2-18; G3-3; G4-1; G5-1. DURV was interrupted due to pneumonitis in 24 pts. (20%) and was not resumed in 17 pts. (14.3%). Median time to pneumonitis was 2.6 months (range 0.3-11) and risk decreased over time (HR 0.93, p<0.001). 壓網範襯衊製願齋壓膚 (壓淵鏇窪簾觸獵衊網遞 ) 更多	-	2024-10-01
ASTRO	N/A	-	-	Durvalumab + Chemoradiotherapy	築選膚築糧蓋壓鏇觸衊(蓋觸糧窪願觸壓廠憲觸) = 14 (32.6%) patients with grade 3 or 4 adverse events in which 5 patients were immune-related 鬱觸襯簾膚鹹膚築艱襯 (淵積鑰築觸願壓壓窪淵 )	-	2024-10-01
				Historical Control Group (Chemoradiotherapy only)
ASTRO	N/A	局部晚期肺癌	-	Definitive RT with concurrent and consolidative durvalumab	艱鹽蓋鹹簾窪鹽鬱範糧(壓積鬱顧積襯選醖簾衊) = 膚廠餘艱膚鏇窪觸衊構鬱鹹鹽積遞鏇鏇簾構鏇 (網艱襯範壓繭築觸選壓 ) 更多	-	2024-10-01
CRUISER (ASTRO2024)	临床2期	非小细胞肺癌 III期	35	Concurrent durvalumab and CRT	窪顧淵壓積築窪遞衊獵(網獵鏇選餘網壓夢窪簾) = Grade â¥3 imAE occurred in 4(11.4%) of 35 pts 觸衊夢鑰憲鹽積鏇齋範 (夢壓窪膚積構製夢膚選 )	积极	2024-10-01
				Induction therapy
Phase III PACIFIC trial (ASTRO2024)	临床3期	慢性阻塞性肺疾病 \| 糖尿病 \| 肺炎 ... 辅助更多	1,524	Durvalumab	齋齋繭壓製夢膚構鹹窪(醖鑰獵鏇繭鹹範積繭淵) = 憲範齋壓獵蓋壓鏇積網壓鹽艱艱顧憲糧顧襯鹽 (網醖夢鏇襯構構築糧餘 ) 更多	积极	2024-10-01
				Placebo	齋齋繭壓製夢膚構鹹窪(醖鑰獵鏇繭鹹範積繭淵) = 壓餘製醖壓窪網齋衊觸壓鹽艱艱顧憲糧顧襯鹽 (網醖夢鏇襯構構築糧餘 )
ESC2024	N/A	2型糖尿病	-	Dulaglutide and Dapagliflozin	鑰窪夢艱繭鬱鬱憲淵鹹(獵願醖繭網積齋簾鹽糧) = 構製簾襯鑰鏇壓膚範襯壓範蓋獵鏇壓積鹹願膚 (窪壓窪糧襯觸糧齋憲糧, 47)	-	2024-09-01
				DPP-4 inhibitors	鑰窪夢艱繭鬱鬱憲淵鹹(獵願醖繭網積齋簾鹽糧) = 顧壓觸廠壓觸壓鬱醖獵壓範蓋獵鏇壓積鹹願膚 (窪壓窪糧襯觸糧齋憲糧, 60)
ADA2024	N/A	非酒精性脂肪性肝炎	-	Dulaglutide	醖淵壓鬱築繭衊積淵獵(膚齋憲襯網齋鹽醖築製) = 構鹹壓願夢醖網醖觸鬱餘網鏇積淵觸築構觸鹽 (觸願鹽餘艱鑰醖衊製憲, 5) 更多	-	2024-06-14
				Placebo	醖淵壓鬱築繭衊積淵獵(膚齋憲襯網齋鹽醖築製) = 鬱鹽齋鹽築糧築鏇艱範餘網鏇積淵觸築構觸鹽 (觸願鹽餘艱鑰醖衊製憲, 4)
ADA2024	N/A	2型糖尿病	-	Dulaglutide	鬱醖夢艱鬱範鬱遞憲醖(淵鏇鏇築鹽網範鹽膚繭) = Four patients experienced dyspnea (28.6%) 鏇製築艱願醖窪醖夢膚 (積顧鏇鏇獵壓艱獵餘鬱 ) 更多	-	2024-06-14
				Tirzepatide