培美曲塞二钠(Pemetrexed Disodium Hydrate) - 药物靶点：DHFR x GART x TYMS_在研适应症：转移性非鳞状非小细胞肺癌，不可切除的胸膜恶性间皮瘤，局部晚期非小细胞肺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

MTA、Multitargeted antifolate、PEMETREXED

+ [23]

靶点

DHFR x GART x TYMS

作用机制

DHFR抑制剂(二氢叶酸还原酶抑制剂)、GART抑制剂(GAR转化酶抑制剂)、TYMS抑制剂(胸苷酸合成酶抑制剂)

治疗领域

肿瘤呼吸系统疾病其他疾病+ [2]

在研适应症

转移性非鳞状非小细胞肺癌不可切除的胸膜恶性间皮瘤局部晚期非小细胞肺癌+ [20]

非在研适应症

腺癌晚期乳腺癌晚期癌症+ [73]

原研机构

Eli Lilly & Co.

在研机构

Janssen Research & Development LLCBaxter Holding BV

Eli Lilly & Co.

+ [28]

非在研机构

KRKA ddSandoz GmbHMenarini International Operations Luxembourg SA

+ [5]

最高研发阶段批准上市

首次获批日期

美国 (2004-02-04),

恶性胸膜间皮瘤

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)、优先审评 (中国)

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结构

分子式C20H35N5Na2O13

InChIKeyPXQGZQUWLRLNRX-MYXYZBIASA-N

CAS号357166-29-1

关联

1,203

项与培美曲塞二钠相关的临床试验

NCT06522360 / Not yet recruiting临床2期IIT

Brigatinib Plus Chemotherapy or Local Consolidation Therapy in ALK Positive Advanced Non-small Cell Lung Cancer (BrightStar-2)

The goal of this clinical research study is to learn if the combination of brigatinib and either local consolidation therapy (such as radiotherapy or surgery) or chemotherapy (pemetrexed and carboplatin) can help to control the disease compared with brigatinib alone. The safety of these combinations will also be studied.

开始日期2025-12-01

申办/合作机构

The University of Texas MD Anderson Cancer Center

NCT06632327 / Not yet recruiting临床3期IIT

Perioperative Versus Adjuvant Systemic Therapy in Patients With Resectable Non-Small Cell Lung Cancer - PROSPECT LUNG

This phase III trial compares standard therapy given after surgery (adjuvant) to standard therapy given before and after surgery (perioperative) in treating patients with stage II-IIIB non-small cell lung cancer (NSCLC) that can be removed by surgery (resectable). The usual approach for patients with resectable NSCLC is chemotherapy and/or immunotherapy before surgery, after surgery, or both before and after surgery. This study is being done to find out which approach is better at treating patients with lung cancer. Treatment will be administered according to the current standard of care at the time of enrollment. Chemotherapy options may include cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and vinorelbine at standard doses according to the treating physician. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid (DNA) and may kill tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells from growing and dividing and may kill them. Other chemotherapy drugs, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading . Immunotherapy with monoclonal antibodies, such as nivolumab, pembrolizumab, and atezolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Starting treatment with chemotherapy and immunotherapy prior to surgery and continuing treatment after surgery may be a more effective treatment option than adjuvant therapy alone in patients with stage II-IIIB resectable NSCLC.

开始日期2025-05-30

申办/合作机构

Alliance for Clinical Trials in Oncology

[+1]

NCT06630416 / Not yet recruiting临床2期IIT

A Phase II Trial to Evaluate Pemetrexed Response in Relation to Tumor Alterations of Gene Status in Patients With Previously Treated Metastatic Urothelial Carcinoma and Other Solid Tumors

This phase II trial tests how well pemetrexed works in treating patients with urothelial bladder cancer and other solid tumors that have spread from where they first started (primary site) to other places in the body (metastatic) with mutations that result in a loss of function in the MLL4-protein/KMT2D-gene or UTX-protein/KDM6A-gene or MTAP enzyme. Loss of function due to a genetic mutation means a gene's activity may be reduced or eliminated. Mutations that result in a loss of function in the MLL4-protein or KMT2D-gene are found in 9.96% of all cancers including bladder carcinoma patients, esophageal squamous cell carcinoma and esophageal adenocarcinoma patients. In addition, mutations that result in a loss of function in the UTX-protein or KDM6A-gene are found in approximately 5% of all tumors, including bladder cancers, endometrial cancer, and esophagogastric cancer amongst many other tumor types. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make deoxyribonucleic acid and may kill tumor cells. Giving pemetrexed may increase response in patients with metastatic urothelial bladder cancer and other solid tumors with the loss of function in the MLL4-protein/KMT2D-gene or UTX-protein/KDM6A-gene or MTAP enzyme.

开始日期2025-05-10

申办/合作机构

Northwestern University

[+1]

100 项与培美曲塞二钠相关的临床结果

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100 项与培美曲塞二钠相关的转化医学

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100 项与培美曲塞二钠相关的专利（医药）

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6,547

项与培美曲塞二钠相关的文献（医药）

2024-12-31·Gut microbes

Article

作者: Chuang, Hsiao-Li ; Lyu, Qiang ; Liu, Po-Yu ; Zou, Hsin-Bai ; Chang, Hsin-Yuan ; Cheng, Wan-Ju ; Hsu, Cheng-Chih ; Sung, Li-Kang ; Chen, Rou-An ; Wu, Hsin-Yi ; Wu, Wei-Kai ; Liu, Lihong ; Wu, Ming-Shiang

Dietary patterns and corresponding gut microbiota profiles are associated with various health conditions. A diet rich in polyphenols, primarily plant-based, has been shown to promote the growth of probiotic bacteria in the gastrointestinal tract, subsequently reducing the risk of metabolic disorders in the host. The beneficial effects of these bacteria are largely due to the specific metabolites they produce, such as short-chain fatty acids and membrane proteins. In this study, we employed a metabolomics-guided bioactive metabolite identification platform that included bioactivity testing using in vitro and in vivo assays to discover a bioactive metabolite produced from probiotic bacteria. Through this approach, we identified 5'-methylthioadenosine (MTA) as a probiotic bacterial-derived metabolite with anti-obesity properties. Furthermore, our findings indicate that MTA administration has several regulatory impacts on liver functions, including modulating fatty acid synthesis and glucose metabolism. The present study elucidates the intricate interplay between dietary habits, gut microbiota, and their resultant metabolites.

2024-12-01·Molecular biology reports

MiR-320a upregulation contributes to the effectiveness of pemetrexed by inhibiting the growth and invasion of human lung cancer cell line (Calu-6)

Article

作者: Esmaeili Gouvarchin Ghaleh, Hadi ; Ghorbani Alvanegh, Akbar ; Mohammad Ganji, Shahla ; Arpanaei, Ayyoob

BACKGROUND:

Lung cancer is a common and deadly disease. Chemotherapy is the most common treatment, which inhibits cancer cell growth. Pemetrexed (PMX) is often used with other drugs. Environmental stress can affect regulatory non-coding RNAs such as MicroRNAs that modify gene expression. This study investigates the effect of PMX on the hsa-miR-320a-3p expression in the Calu-6 lung cancer cell line.

METHODS AND RESULT:

Calu-6 cells were cultured in an incubator with 37 °C, 5% CO2, and 98% humidity. The MTT test was performed to determine the concentration of PMX required to inhibit 50% of cell growth. To examine growth inhibition and apoptosis, release of lactate dehydrogenase (LDH), cell assays and caspase 3 and 7 enzyme activity were used. Finally, molecular studies were conducted to compare the expression of hsa-miR-320a-3p and genes including VDAC1, DHFR, STAT3, BAX and BCL2 before and after therapy.

RESULTS:

According to a study, it has been observed that PMX therapy significantly increases LDH release after 24 h. The study found that PMX's IC₅₀ on Calu-6 is 8.870 µM. In addition, the treated sample showed higher expression of hsa-miR-320a-3p and BAX, while the expression of VDAC1, STAT3, DHFR and BCL2 decreased compared to the control sample.

CONCLUSION:

According to the findings of the current research, hsa-miR-320a-3p seems to have the potential to play an important role in the development of novel approaches to the treatment of lung cancer.

2024-11-01·Clinical Lung Cancer

The Design for a Phase II, Randomized, Multicenter Study of CtDNA-Guided Treatment With Furmonertinib Combined Therapy or Furmonertinib Alone for Untreated Advanced EGFR Mutant Non–small-cell Lung Cancer Patients: The FOCUS-C Study

Article

作者: Chen, Zihong ; Zhang, Li ; Fang, Wenfeng ; Huang, Yan ; Chen, Gang ; Zhang, Yaxiong ; Yang, Yunpeng

BACKGROUND:

Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have significant antitumor activity to advanced non-small-cell lung cancer (NSCLC) patients with classic EGFR mutations. However, EGFR-TKI monotherapy shows poor efficacy in patients whose circulating tumor cell DNA (ctDNA) of EGFR mutations cannot be rapidly cleared.

MATERIALS AND METHODS:

As a third-generation TKI, furmonertinib has shown superior antitumor activity and minor toxicity. The FOCUS-C study is a prospective, multicenter, randomized controlled trial (NCT05334277) to explore the efficacy and safety of furmonertinib plus pemetrexed-platinum doublet chemotherapy with or without bevacizumab versus furmonertinib monotherapy in untreated advanced EGFR mutant NSCLC patients without EGFR clearance after the induction therapy of furmonertinib. Patients with EGFR clearance will still receive furmonertinib as Arm A. Patients without ctDNA clearance will be randomized in a 2:2:1 ratio as Arm B1 (furmonertinib), Arm B2 (furmonertinib combined with carboplatin and pemetrexed for 4 cycles, and then furmonertinib and pemetrexed as maintenance therapy) and Arm B3 (Arm B2 regimen plus bevacizumab). The primary endpoint is progression-free survival (PFS) in Arm B2/B1. Secondary endpoints include PFS in Arm B3/B1, PFS in Arm A/B1, PFS in Arm B3/B2, objective response and disease control rate, overall survival and safety in all Arms. Exploratory endpoints are focused on the efficacy based on plasma NGS at different timepoints.

CONCLUSION:

This study will evaluate the efficacy and tolerability of furmonertinib plus carboplatin and pemetrexed with or without bevacizumab verses furmonertinib alone in untreated patients with advanced EGFR mutant NSCLC without EGFR clearance.

1,092

项与培美曲塞二钠相关的新闻（医药）

2024-11-15

·美通社

君实生物特瑞普利单抗EXTENTORCH研究在国际权威期刊JAMA子刊发表

上海 2024年11月15日 /美通社/ -- 由吉林省肿瘤医院程颖教授牵头开展的特瑞普利单抗联合化疗一线治疗广泛期小细胞肺癌 (ES-SCLC) 的 III期EXTENTORCH研究结果发表在国际肿瘤学顶级期刊《美国医学会杂志· 肿瘤学》 ( JAMA Oncology ，IF 2023 =22.5），为ES-SCLC一线免疫治疗再添重磅循证医学证据。程颖教授为本文的第一作者和通讯作者。来源：JAMA期刊官网 EXTENTORCH研究（NCT04012606）是一项多中心、随机、双盲、安慰剂对照的III期临床研究，旨在比较特瑞普利单抗或安慰剂联合依托泊苷及铂类一线治疗ES-SCLC的有效性和安全性。 EXTENTORCH研究主要研究者，吉林省肿瘤医院程颖教授表示："EXTENTORCH研究作为ES-SCLC领域全球首个成功达到预设双主要研究终点阳性结果的抗PD-1单抗的Ⅲ期临床研究，是ES-SCLC治疗的又一次关键突破。试验组1年PFS率提升近4倍，所有亚组患者均有获益，主要终点之一的OS取得阳性结果，成功通过了临床‘金标准’的考核，为患者带来确切生存获益。本次EXTENTORCH研究见刊不仅公布了特瑞普利单抗联合化疗一线治疗ES-SCLC的疗效数据，更重要的是，这项研究进行了分子层面的探索，对筛选接受免疫治疗的患者具有重要的指导意义。" 2023年5月，EXTENTORCH研究主要终点无进展生存期（PFS）和总生存期（OS）均达到方案预设的优效边界，特瑞普利单抗由此成为全球首个在ES-SCLC一线治疗III期研究中取得预设双重主要终点阳性结果的PD-1抑制剂。 2024年6月，基于该研究的积极结果，特瑞普利单抗获国家药品监督管理局（ NMPA）正式批准联合依托泊苷和铂类用于ES-SCLC一线治疗，并获中国临床肿瘤学会（CSCO）两大指南推荐为ES-SCLC一线治疗优选方案，为中国ES-SCLC患者提供了治疗新选择。此前，EXTENTORCH研究以口头报告的形式在2023年ESMO大会上首次公布了研究数据，此次全文发表于国际期刊，彰显了国际学者对这项研究及特瑞普利单抗的肯定，结果显示：与单纯化疗相比，特瑞普利单抗联合化疗显著改善患者 PFS和OS，将疾病进展或死亡风险降低33% （HR=0.67；95% CI， 0.54-0.82），死亡风险降低了 20% （HR=0.80；95% CI， 0.65-0.98）。亚组分析显示，所有关键亚组均显示出一致的 PFS和OS获益。生物标志物探索分析显示，在特瑞普利单抗联合化疗组中，具有低肿瘤内异质性（ITH）， HLA-A11 + HLA-B62 - 单倍型， KMT2D 和COL4A4 野生型，或 CTNNA2/SCN4A 序列变异的患者的临床获益更明显。特瑞普利单抗联合化疗的安全性良好，未发现新的安全信号。两组在治疗期间出现的不良事件（TEAE，99.5%vs100%）和≥3级TEAE（89.6%vs89.4%）的发生率相似。君实生物总经理兼首席执行官邹建军博士表示: “此次EXTENTORCH的重磅研究成果获得《美国医学会杂志·肿瘤学》发表，体现了国际学术界对以特瑞普利单抗为代表的免疫治疗在ES-SCLC患者一线治疗中的价值认可。肺癌一直是公司重点关注的疾病领域，截至目前，特瑞普利单抗已成功获批包括非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）在内的3项适应症，覆盖了早中期（围手术期）至晚期人群，管线内也还有其他产品正处于攻关阶段，我们会积极推进相关工作，期待能为全球肺癌患者带来更多更优的创新方案。" 1. 本材料旨在传递前沿信息，无意向您做任何产品的推广，不作为临床用药指导。 2. 若您想了解具体疾病诊疗信息，请遵从医疗卫生专业人士的意见与指导。关于 EXTENTORCH研究 EXTENTORCH研究（NCT04012606）是一项多中心、随机、双盲、安慰剂对照的III期临床研究，旨在比较特瑞普利单抗或安慰剂联合依托泊苷及铂类一线治疗ES-SCLC的有效性和安全性。研究纳入既往未接受系统治疗的ES-SCLC患者，以1:1的比例随机接受特瑞普利单抗（240mg, Q3W）或安慰剂联合依托泊苷（100mg/m 2 ， Q3W）和铂类（顺铂 75 mg/m 2 或卡铂 AUC 5 mg/mL/min， Q3W）治疗4~6个周期，之后接受特瑞普利单抗或安慰剂维持治疗，直至疾病进展、出现不可耐受的毒性或完成2年治疗。研究分层因素包括性别和基线ECOG体能状况评分。主要终点为研究者根据RECIST v1.1评估的PFS和OS。次要终点包括盲态独立中心审查（BICR）评估的PFS、客观缓解率（ORR）、疾病控制率（DCR）、疾病缓解率（DOR）和安全性等。探索性终点包括PD-L1的表达、肿瘤突变负荷（TMB）和其他基于测序的与临床疗效相关的生物标志物。自2019年9月至2021年5月，研究共纳入442例ES-SCLC患者，随机分配至特瑞普利单抗联合化疗组（n=223）或安慰剂联合化疗组（n=219）。该研究由程颖教授担任主要研究者，在全国49家临床中心联合开展。关于特瑞普利单抗注射液（拓益 ® ）特瑞普利单抗注射液（拓益 ® ）作为我国批准上市的首个国产以PD-1为靶点的单抗药物，获得国家科技重大专项项目支持，并荣膺国家专利领域最高奖项"中国专利金奖"。特瑞普利单抗至今已在全球（包括中国、美国、东南亚及欧洲等地）开展了覆盖超过15个适应症的40多项由公司发起的临床研究。正在进行或已完成的关键注册临床研究在多个瘤种范围内评估特瑞普利单抗的安全性及疗效，包括肺癌、鼻咽癌、食管癌、胃癌、膀胱癌、乳腺癌、肝癌、肾癌及皮肤癌等。截至目前，特瑞普利单抗已在中国内地获批10项适应症：用于既往接受全身系统治疗失败的不可切除或转移性黑色素瘤的治疗（2018年12月）；用于既往接受过二线及以上系统治疗失败的复发/转移性鼻咽癌患者的治疗（2021年2月）；用于含铂化疗失败包括新辅助或辅助化疗12个月内进展的局部晚期或转移性尿路上皮癌的治疗（2021年4月）；联合顺铂和吉西他滨用于局部复发或转移性鼻咽癌患者的一线治疗（2021年11月）；联合紫杉醇和顺铂用于不可切除局部晚期/复发或远处转移性食管鳞癌患者的一线治疗（2022年5月）；联合培美曲塞和铂类用于表皮生长因子受体（EGFR）基因突变阴性和间变性淋巴瘤激酶（ALK）阴性、不可手术切除的局部晚期或转移性非鳞状非小细胞肺癌的一线治疗（2022年9月）；联合化疗围手术期治疗，继之本品单药作为辅助治疗，用于可切除IIIA-IIIB期非小细胞肺癌的成人患者（2023年12月）；联合阿昔替尼用于中高危的不可切除或转移性肾细胞癌患者的一线治疗（2024年4月）；联合依托泊苷和铂类用于广泛期小细胞肺癌一线治疗（2024年6月）；联合注射用紫杉醇（白蛋白结合型）用于经充分验证的检测评估PD-L1阳性（CPS≥1）的复发或转移性三阴性乳腺癌的一线治疗（2024年6月）。2020年12月，特瑞普利单抗首次通过国家医保谈判，目前已有6项获批适应症纳入《国家医保目录（2023年）》，是目录中唯一用于治疗黑色素瘤的抗PD-1单抗药物。2024年10月，特瑞普利单抗用于复发/转移性鼻咽癌治疗的适应症在中国香港获批。在国际化布局方面，特瑞普利单抗已作为首款鼻咽癌药物在美国和印度获批上市，其用于晚期鼻咽癌和食管鳞癌的一线治疗获得欧盟委员会批准上市。此外，英国药品和保健品管理局（MHRA）受理了特瑞普利单抗联合顺铂和吉西他滨用于局部复发或转移性鼻咽癌患者的一线治疗以及联合紫杉醇和顺铂用于不可切除局部晚期/复发或转移性食管鳞癌患者的一线治疗的上市许可申请，澳大利亚药品管理局（TGA）和新加坡卫生科学局（HSA）分别受理了特瑞普利单抗联合顺铂/吉西他滨作为转移性或复发性局部晚期鼻咽癌成人患者的一线治疗，以及作为单药治疗既往含铂治疗过程中或治疗后疾病进展的复发性、不可切除或转移性鼻咽癌的成人患者的上市许可申请。关于君实生物君实生物（688180.SH, 1877.HK）成立于2012年12月，是一家以创新为驱动，致力于创新疗法的发现、开发和商业化的生物制药公司。依托全球一体化源头创新研发能力，公司已构建起涵盖超过50款创新药物的多层次产品管线，覆盖恶性肿瘤、自身免疫、慢性代谢类、神经系统、感染性疾病五大治疗领域，已有5款产品在国内或海外上市，包括我国首个自主研发、在中美欧等地超过30个国家和地区获批上市的PD-1抑制剂特瑞普利单抗（拓益 ® ），临床开发阶段的药物超过30款。疫情期间，君实生物还参与开发了埃特司韦单抗、民得维 ® 等多款预防和治疗新冠的创新药物，积极承担本土创新药企的责任。君实生物以"用世界一流、值得信赖的创新药普惠患者"为使命，立足中国，布局全球。目前，公司在全球拥有约2500名员工，分布在美国旧金山和马里兰，中国上海、苏州、北京、广州等。官方网站： www.junshipharma.com 官方微信：君实生物

CSCO会议临床3期临床结果免疫疗法上市后研究

2024-11-14

·GlobeNewswire-Health Care

Immutep’s Efti Shows Excellent Survival Data from INSIGHT-003 Trial in Non-Small Cell Lung Cancer

Media Release Mature data in patients with a minimum follow-up of 22 months (N=21) shows excellent results, well above historical controls and exceeding expectations: Median Overall Survival is 32.9 months, with median Progression Free Survival reaching 12.7 months, and a 24-month Overall Survival rate of 81.0% Data from all evaluable patients to date (N=40) demonstrates significant improvement of Overall Response Rate compared to historical controlsSafety continues to be favourable with no new safety signalsINSIGHT-003, which is nearing completion of enrolment, evaluates efti with the most widely used immunotherapy-chemo combination today in a similar population to upcoming TACTI-004 Phase III trial SYDNEY, AUSTRALIA, Nov. 14, 2024 (GLOBE NEWSWIRE) -- Immutep Limited (ASX: IMM; NASDAQ: IMMP) (“Immutep” or “the Company”), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, today announces positive data from the investigator-initiated INSIGHT-003 Phase I trial evaluating eftilagimod alpha (efti) in combination with KEYTRUDA® (pembrolizumab) and chemotherapy for first-line treatment of metastatic non-squamous non-small cell lung cancer (1L NSCLC) patients. Prof. Dr. Salah-Eddin Al-Batran of the Frankfurt Institute of Clinical Cancer Research (IKF) and project lead stated, “The strength of these mature survival results coupled with a favourable safety profile in first-line treatment of patients with non-squamous NSCLC, the vast majority of whom have negative or low PD-L1 expression, is very encouraging. This promising data in INSIGHT-003 suggests a complementary effect from the addition of efti, a unique MHC Class II agonist, to the standard-of-care combination of pembrolizumab and chemotherapy which has revolutionised the treatment landscape in lung cancer. The IKF will also support and is looking forward to participating in the upcoming TACTI-004 study, which has PFS and OS as dual primary endpoints.” Key Results - Data cutoff - 15 October 2024The survival data from the triple combination therapy in patients irrespective of PD-L1 expression with a minimum follow-up of 22 months (N=21) at data cut-off shows: INSIGHT-003 ResultsMedian Overall Survival (OS)32.9 monthsMedian Progression-Free Survival (PFS)12.7 months24-month Overall Survival (OS)81.0% These results compare favourably to the 22.0-month median OS, 9.0-month median PFS, and 24-month OS rate of 45.5% from a registrational trial of anti-PD-1 and doublet chemotherapy in non-squamous 1L NSCLC regardless of PD-L1 expression.1 Notably, ~19% of the 21 patients in INSIGHT-003 with mature survival data have high PD-L1 expression, who typically respond better to anti-PD-1 therapy, versus ~32% in the registrational trial of anti-PD-1 and doublet chemotherapy. Marc Voigt, CEO of Immutep, stated, “The overall survival and progression-free survival data from this mature cohort of patients in INSIGHT-003 with nearly a 2-year minimum follow-up exceeds our expectations. We are encouraged to see efti build upon the historical clinical outcomes from the most widely used immunotherapy-chemo combination today. Additionally, the early evaluations in the expansion cohort of 19 patients, who all have low or negative PD-L1 expression, are tracking well and we look forward to additional data updates from the INSIGHT-003 trial in 2025 and beyond. Our focus on potentially driving a new standard of care globally in first line treatment of NSCLC is boosted by these results and we are well advanced in our preparations to initiate the TACTI-004 Phase III trial.” Data from all evaluable patients to date (N=40) demonstrates significant improvement of Overall Response Rate (ORR) according to RECIST 1.1 across all levels of PD-L1 expression compared to historical control2: 75.0% ORR versus 62.1% ORR in patients with high PD-L1 expression (TPS >50%)58.8% ORR versus 49.2% ORR in patients with low PD-L1 expression (TPS 1-49%)47.4% ORR versus 32.3% ORR in patients with negative PD-L1 expression (TPS <1%) In this all-comer PD-L1 trial, the 55.0% ORR and 87.5% Disease Control Rate (DCR) are from the following breakdown of patients by PD-L1 expression: TPS >50% (N=4), TPS 1-49% (N=17), and TPS <1% (N=19). As compared to the general 1L NSCLC patient population of which each of these PD-L1 levels represents roughly one-third, INSIGHT-003 is biased towards low and negative PD-L1 (TPS <50%) patients who are typically less responsive to anti-PD-1 therapy. In these patients with low and negative PD-L1 expression (36 of 40 patients), the triple combination achieved a 52.8% ORR and 86.1% DCR. Of note, all 19 patients in the expansion cohort have TPS <50% and several with stable disease have potential to become responders. SafetySafety continues to be favourable for efti in combination with pembrolizumab and chemotherapy, with no new safety signals. Next StepsINSIGHT-003, a multi-centre study led by the Frankfurt Institute of Clinical Cancer Research IKF, is nearing completion of patient enrolment. Additional data updates from this trial are expected in 2025 and beyond. About INSIGHT-003INSIGHT-003 is an investigator-initiated, multi-centre study led by the Frankfurt Institute of Clinical Cancer Research (IKF). It is being run as the third arm (Stratum C) of the ongoing Phase I INSIGHT trial with Prof. Dr. Salah-Eddin Al-Batran as lead investigator. The study is evaluating a triple combination therapy in front line non-small cell lung cancer patients consisting of efti administered subcutaneously in conjunction with an existing approved standard-of-care combination of anti-PD-1 therapy (pembrolizumab) and doublet chemotherapy (carboplatin and pemetrexed) delivered intravenously. The trial will assess the safety, tolerability, and initial efficacy of the combination. About ImmutepImmutep is a clinical-stage biotechnology company developing novel LAG-3 immunotherapy for cancer and autoimmune disease. We are pioneers in the understanding and advancement of therapeutics related to Lymphocyte Activation Gene-3 (LAG-3), and our diversified product portfolio harnesses its unique ability to stimulate or suppress the immune response. Immutep is dedicated to leveraging its expertise to bring innovative treatment options to patients in need and to maximise value for shareholders. For more information, please visit www.immutep.com. Australian Investors/Media:Catherine Strong, Sodali & Co.+61 (0)406 759 268; catherine.strong@sodali.com U.S. Media:Chris Basta, VP, Investor Relations and Corporate Communications+1 (631) 318 4000; chris.basta@immutep.com 1, 2. Shirish Gadgeel et al., Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non–Small-Cell Lung Cancer. JCO 38, 1505-1517(2020).DOI:10.1200/JCO.19.03136 KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

临床结果免疫疗法临床3期临床1期

2024-11-14

·癌度

抗癌药新组合：PD-1抑制剂联合奥拉帕利治疗驱动基因阴性肺癌遭遇滑铁卢！

大多数非小细胞肺癌确诊的时候处于晚期，无法进行手术治疗。如果患者没有靶向药的治疗机会，那么唯一的机会就是免疫检查点抑制剂，如果不是PD-L1高表达，则还需要将PD-1联合铂类化疗进行组合，总体来说免疫治疗的出现改善了患者的生存期。对于没有EGFR或ALK基因突变的肺癌，PD-1抑制剂联合培美曲塞和铂类化疗是晚期非小细胞肺癌的一线标准治疗。而且患者使用这些药物组合起效，则生存期超过5年的概率更大。奥拉帕利是一种PARP抑制剂，对于乳腺癌和卵巢癌表现出较好的治疗活性。临床前的研究表明，PARP抑制剂可以通过激活干扰素通路和促进免疫细胞浸润肿瘤微环境，来诱导免疫原反应。PARP抑制剂还可以上调PD-L1表达，所以就有了将PARP抑制剂和PD-1抑制剂联合使用的思路。下面就是一项三期临床试验，研究PD-1抑制剂帕博利珠单抗联合奥拉帕利，或帕博利珠单抗联合培美曲塞进行维持治疗，以判断联合治疗的思路。 1、PD-1和PARP抑制剂联合的疗效这是一项三期临床试验，入组的患者为晚期非鳞状非小细胞肺癌，这些患者没有驱动性基因突变且没有经过系统治疗。这些患者首先使用PD-1抑制剂帕博利珠单抗联合培美曲塞和卡铂或顺铂治疗4个周期，对于治疗产生完全缓解、部分缓解或病情稳定的患者分为两组。一组患者每天两次口服奥拉帕利（每次300毫克），每3周使用PD-1抑制剂帕博利珠单抗。另外一组患者属于对照组，则是每3周使用帕博利珠单抗联合培美曲塞。也就是两组患者的治疗区别是维持治疗的药物。这项临床试验入组的患者很多，1003名患者选出了672名患者分为了两组。中位随访时间达到了39.9个月，结果如上面的图示，奥拉帕利联合PD-1的中位无进展生存时间是7.1个月，PD-1联合培美曲塞的中位无进展生存时间是8.3个月，没有显著区别。两组患者的中位总生存时间分别是20.7个月和23个月，也是没有显著区别。也就是这个研究的结论是没有达到预期的终点。安全性方面，3级以上治疗相关不良事件的发生率分别是26.1%和30%。 2、启发和讨论这个研究属于耗资比较大的三期临床试验，但是很遗憾没有达到预期的结果。也就是在临床前探索的PARP抑制剂与PD-1的组合没有达到更好的预期，当然如果能达到预期则患者可以不需要打化疗了，可能这是比较具有吸引力的。但研究结果如此可能也确实没有更好的办法了。不过后面关于这两种药物的组合是否有新的思路或数据我们拭目以待。但是上面的研究结论请大家注意，避免不必要的联合用药错误。欢迎关注癌度，了解全球肿瘤诊疗的最新进展！癌度与吉因加启动的“基因检测人人可及”计划里，仅需要3000元就能检测36个基因，大家可以联系癌度或扫描上面的二维码咨询癌度医学顾问，了解基因检测的相关问题。参考文献： Gray JE, et al., The Phase 3 KEYLYNK-006 Study of Pembrolizumab plus Olaparib versus Pembrolizumab plus Pemetrexed as Maintenance Therapy for Metastatic Nonsquamous Non–Small-Cell Lung Cancer, Journal of Thoracic Oncology (2024), 往期推荐抗癌新药SY-5007首次人体临床试验数据报道，治疗多种肿瘤产生积极疗效！抗癌病毒治疗在脑瘤试验中显示出希望，有患者可见病灶消失！遗憾！免疫治疗药物度伐利尤单抗治疗PD-L1高表达肺癌，未能改善总生存时间！最新临床研究：强效新疗法使晚期乳腺癌的无进展生存期翻倍！

免疫疗法临床3期临床结果加速审批

100 项与培美曲塞二钠相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	培美曲塞二钠	L01BA04	DB00642

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
转移性非鳞状非小细胞肺癌	美国	Hospira, Inc.	2022-06-10
局部晚期非小细胞肺癌	欧盟	Sandoz GmbH	2015-09-18
局部晚期非小细胞肺癌	冰岛	Sandoz GmbH	2015-09-18
局部晚期非小细胞肺癌	列支敦士登	Sandoz GmbH	2015-09-18
局部晚期非小细胞肺癌	挪威	Sandoz GmbH	2015-09-18
转移性非小细胞肺癌	欧盟	Sandoz GmbH	2015-09-18
转移性非小细胞肺癌	冰岛	Sandoz GmbH	2015-09-18
转移性非小细胞肺癌	列支敦士登	Sandoz GmbH	2015-09-18
转移性非小细胞肺癌	挪威	Sandoz GmbH	2015-09-18
不可切除的胸膜恶性间皮瘤	欧盟	Sandoz GmbH	2015-09-18
不可切除的胸膜恶性间皮瘤	冰岛	Sandoz GmbH	2015-09-18
不可切除的胸膜恶性间皮瘤	列支敦士登	Sandoz GmbH	2015-09-18
不可切除的胸膜恶性间皮瘤	挪威	Sandoz GmbH	2015-09-18
非鳞状非小细胞肺癌	美国	Eli Lilly & Co.	2009-07-02
间皮瘤	美国	Eli Lilly & Co.	2004-08-19
非小细胞肺癌	美国	Eli Lilly & Co.	2004-08-19
恶性胸膜间皮瘤	美国	Eli Lilly & Co.	2004-02-04

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
KRAS G12C突变非小细胞肺癌	临床3期	美国	Eli Lilly & Co.	2023-12-21
KRAS G12C突变非小细胞肺癌	临床3期	中国	Eli Lilly & Co.	2023-12-21
KRAS G12C突变非小细胞肺癌	临床3期	日本	Eli Lilly & Co.	2023-12-21
KRAS G12C突变非小细胞肺癌	临床3期	澳大利亚	Eli Lilly & Co.	2023-12-21
KRAS G12C突变非小细胞肺癌	临床3期	奥地利	Eli Lilly & Co.	2023-12-21
KRAS G12C突变非小细胞肺癌	临床3期	比利时	Eli Lilly & Co.	2023-12-21
KRAS G12C突变非小细胞肺癌	临床3期	巴西	Eli Lilly & Co.	2023-12-21
KRAS G12C突变非小细胞肺癌	临床3期	加拿大	Eli Lilly & Co.	2023-12-21
KRAS G12C突变非小细胞肺癌	临床3期	捷克	Eli Lilly & Co.	2023-12-21
KRAS G12C突变非小细胞肺癌	临床3期	丹麦	Eli Lilly & Co.	2023-12-21

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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


NCT04964960 (CTgov)	临床2期	代谢综合征 \| 非小细胞肺癌 \| 脑转移瘤	3	nab paclitaxel+Carboplatin+Paclitaxel+Pembrolizumab+Pemetrexed	遞製膚觸顧襯範餘壓憲(鹹憲鹽願夢窪獵積窪淵) = 蓋觸廠壓鑰憲鹽鬱願構齋範製構鹹遞憲餘獵窪 (願遞顧廠艱餘願餘憲壓, 繭簾網繭選顧鏇積鏇蓋 ~ 糧襯廠觸願鬱築醖鹹選) 更多	-	2024-10-21
NCT01088906 (Phalcis, CTgov)	临床2期	晚期肺非小细胞鳞癌 \| 非鳞状非小细胞肺癌	57	Cisplatin+Pemetrexed (EXPERIMENTAL ARM)	餘膚築鑰觸製蓋觸構遞(鏇顧窪鬱簾簾繭觸觸廠) = 醖遞齋壓蓋糧繭遞壓簾觸鏇壓鬱範築範艱顧膚 (願獵淵遞鬱積獵糧衊顧, 壓願製壓壓膚憲膚願繭 ~ 顧範鏇窪糧淵壓簾艱淵) 更多	-	2024-10-15
				Cisplatin+Pemetrexed (Experimental Arm: Pemetrexed Plus Cisplatin)	夢製顧遞鑰淵夢廠鹽艱(夢遞齋蓋獵襯築願憲廠) = 淵壓製鏇製襯齋窪糧齋壓鹹鑰廠鏇網餘鹽獵鹹 (鏇壓繭襯鬱鑰夢簾壓顧, 餘構繭鬱構製壓醖齋糧 ~ 網簾選衊淵艱築膚淵夢) 更多
WCLC2024 人工标引	N/A	恶性胸膜间皮瘤二线 \| 一线	267	first-line Nivolumab plus Ipilimumab, second-line platinum-based/pemetrexed	糧憲網鹽壓構壓餘齋網(顧鏇餘鬱廠構艱網襯願) = 窪遞膚遞淵構選鑰襯製鏇醖糧簾艱廠壓網餘積 (蓋積齋觸築夢膚觸觸製, 7.7 ~ 8.5)	积极	2024-09-09
NCT04335292 (OCELOT, WCLC2024) 人工标引	临床2期	EGFR突变肺癌二线 EGFR Mutation	29	platinum (carboplatin or cisplatin) + pemetrexed	餘襯襯構鹽衊簾鑰艱壓(顧鬱餘觸醖衊廠齋壓鹹) = 淵鑰壓簾壓醖積遞廠構醖衊顧製網艱衊範顧蓋 (膚獵築願糧製獵網艱範 ) 更多	积极	2024-09-08
				platinum (carboplatin or cisplatin) + pemetrexed (uncommon EGFR mutations)	餘襯襯構鹽衊簾鑰艱壓(顧鬱餘觸醖衊廠齋壓鹹) = 鬱簾壓齋遞網醖壓獵製醖衊顧製網艱衊範顧蓋 (膚獵築願糧製獵網艱範 ) 更多
NCT04035486 (FLAURA2, CTgov)	临床3期	EGFR阳性非小细胞肺癌	587	Carboplatin+Pemetrexed+AZD9291 (Safety Run-In: AZD9291 + Carboplatin + Pemetrexed)	鏇築簾範選蓋鑰願遞範(糧廠憲膚膚顧憲醖鹹顧) = 膚鏇積繭夢顧醖觸淵廠築蓋顧構淵繭廠積積醖 (夢簾簾壓醖網蓋艱範衊, 繭壓醖齋觸鹹衊鑰顧憲 ~ 積觸鹽艱顧衊壓構夢膚) 更多	-	2024-08-06
				Cisplatin+Pemetrexed+AZD9291 (Safety Run-In: AZD9291 + Cisplatin + Pemetrexed)	鏇築簾範選蓋鑰願遞範(糧廠憲膚膚顧憲醖鹹顧) = 願夢積夢願顧鹹淵蓋鹹築蓋顧構淵繭廠積積醖 (夢簾簾壓醖網蓋艱範衊, 襯觸醖憲壓觸襯餘製鹽 ~ 製糧衊鹹網觸淵鹹糧夢) 更多
JPRN-jRCT2051210086 (SCARLET study, ASCO2024)	临床2期	KRAS G12C突变非鳞状非小细胞肺癌 PD-L1 expression level \| KRAS G12C \| TP53 mutation ... 更多	30	Sotorasib plus carboplatin-pemetrexed	廠繭範觸遞鹹願顧顧艱(範衊襯鏇繭壓簾窪膚鹽) = 憲鏇餘選膚襯夢獵顧艱醖襯製鑰廠衊衊艱觸鹽 (遞餘獵窪鑰鑰簾繭醖願, 78.5-94.8 ~ 70.8-97.6) 更多	积极	2024-05-24
ASCO2024	N/A	晚期非小细胞肺癌	-	Pemetrexed plus platinum (AP) morning infusion	鏇糧鬱簾糧鹹鏇艱糧製(製膚選範願鬱鏇廠蓋醖) = 蓋獵醖網鏇壓獵鬱廠壓齋餘範膚築鹽積鏇選廠 (鹽糧願艱醖繭餘鹹遞醖 ) 更多	积极	2024-05-24
				Pemetrexed plus platinum (AP) afternoon infusion	鏇糧鬱簾糧鹹鏇艱糧製(製膚選範願鬱鏇廠蓋醖) = 顧廠積鏇範繭鹽製選顧齋餘範膚築鹽積鏇選廠 (鹽糧願艱醖繭餘鹹遞醖 ) 更多
ASCO2024	N/A	转移性非鳞状非小细胞肺癌维持	121	Maintenance pemetrexed and pembrolizumab	艱觸齋淵觸廠艱鹹鏇齋(鏇壓艱構願襯遞簾鏇鏇) = 網獵簾膚艱鬱齋齋觸遞窪壓鬱壓襯選構鏇艱構 (鹽窪廠顧繭夢選選糧範, 13.8 ~ NA) 更多	积极	2024-05-24
				Maintenance pemetrexed cessation	艱觸齋淵觸廠艱鹹鏇齋(鏇壓艱構願襯遞簾鏇鏇) = 構衊餘鑰觸艱網憲蓋廠窪壓鬱壓襯選構鏇艱構 (鹽窪廠顧繭夢選選糧範, 26.9 ~ NA) 更多
NCT03319537 (CTgov)	临床1/2期	恶性间皮瘤	9	pevonedistat (Pevonedistat)	觸簾鏇膚選鬱齋醖蓋積(獵觸顧壓蓋窪醖願簾遞) = 蓋窪顧襯選廠簾膚廠網窪窪夢願顧齋艱餘餘網 (衊獵醖夢鏇製膚夢鬱膚, 襯壓夢廠選製窪窪艱築 ~ 鹽餘鏇鑰顧繭餘鏇壓壓) 更多	-	2024-05-23
				cisplatin+pevonedistat+pemetrexed (Pevonedistat in Combination With Pemetrexed and Cisplatin)	繭襯範鹹範選顧鹽願構(繭膚構範窪醖遞簾膚鹽) = 艱遞糧壓遞鬱餘鬱簾衊艱襯築艱襯餘憲獵憲簾 (構艱夢鑰網鏇範網繭鏇, 製鑰襯範鑰窪鑰範製繭 ~ 網觸選壓鏇構顧製襯淵) 更多
NCT04956692 (MK-3475-A86, CTgov)	临床3期	转移性非鳞状非小细胞肺癌	531	nab-paclitaxel+Carboplatin+Paclitaxel+cisplatin+Pembrolizumab SC+Pemetrexed (Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy)	鹹獵簾蓋夢衊網廠製憲(積築製襯壓網築衊鏇襯) = 願鬱衊壓糧夢憲醖獵鹽願鑰餘遞艱艱夢積窪願 (淵構醖遞蓋蓋積積繭醖, 積淵繭觸鏇繭鬱糧簾鏇 ~ 窪夢積構淵願願鹹願鬱) 更多	-	2024-05-17
				nab-paclitaxel+Carboplatin+Paclitaxel+cisplatin+Pembrolizumab IV+Pemetrexed (Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy)	鹹獵簾蓋夢衊網廠製憲(積築製襯壓網築衊鏇襯) = 廠衊糧膚蓋餘選壓夢餘願鑰餘遞艱艱夢積窪願 (淵構醖遞蓋蓋積積繭醖, 遞窪範艱壓糧蓋遞憲鹹 ~ 憲構簾鏇範鹹簾製淵製) 更多