This early phase I trial studies the side effects of implanting and removing a microdevice in patients with sarcomas that have spread to other places in the body (metastatic) or have come back (recurrent). Microdevices are rice-sized devices that are implanted into tumor tissue and are loaded with 10 different drugs that are delivered at very small doses, or "microdoses," which may only affect a very small, local area inside the tumor. The purpose of this study is to determine which drugs delivered in the microdevice affect tumor tissue in patients with sarcomas.

开始日期2025-02-25

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

NCT04129151

/ Terminated临床2期IIT

Phase 2 Trial of Palbociclib and Ganitumab in Patients With Relapsed or Refractory Ewing Sarcoma

This research study is designed to study the combination of two drugs, palbociclib and ganitumab, as a potential treatment for Ewing sarcoma.
The names of the study drugs involved in this study are:
* Palbociclib
* Ganitumab

开始日期2019-12-05

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+2]

NCT03041701

/ Terminated临床1/2期IIT

A Phase I/II Trial of the Insulin-Like Growth Factor 1 Receptor (IGF-1R) Antibody AMG479 (Ganitumab) in Combination With the Src Family Kinase (SFK) Inhibitor Dasatinib in Patients With Embryonal and Alveolar Rhabdomyosarcoma

Background:
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood. Two types are embryonal RMS (ERMS) and alveolar RMS (ARMS). Dasatinib may block over-expression of a certain enzyme. Ganitumab may block a certain growth factor, which might suppress tumor growth. This drug combination may help slow tumor growth in people with ERMS and ARMS.
Objective:
To see if dasatinib combined with ganitumab is safe and shrinks or slows the growth of tumors in people with ERMS and ARMS.
Eligibility:
People any age who have ERMS or ARMS that did not respond to previous treatment and who can swallow tablets
Design:
Participants will be screened with:
* Medical history
* Physical exam
* Blood, urine, and heart tests
* Scans/x-rays
* Tissue sample: This can be from previous surgery or biopsy.
* Optional biopsy: A small piece of the tumor is removed with a needle.
Participants will be asked to co-enroll in another protocol.
Participants will get a drug interaction handout and wallet card that show what foods and medications to avoid.
Participants will be treated in cycles. The first cycle is 35 days, and the rest are 28 days. Participants will take dasatinib by mouth daily. They will get ganitumab through an intravenous (IV) every 2 weeks. They will have a physical exam every 1-2 weeks, and urine and heart tests before most cycles.
Participants will continue treatment as long as they do not have severe side effects, or their tumors do not get worse.
After ending treatment, participants will have a visit. This includes repeats of the screening tests.

开始日期2017-07-07

申办/合作机构

National Cancer Institute

100 项与盖尼塔单抗相关的临床结果

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100 项与盖尼塔单抗相关的专利（医药）

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项与盖尼塔单抗相关的文献（医药）

2025-10-15·CLINICAL CANCER RESEARCH

Immune and Growth Factor Signaling Pathways Are Associated with Pathologic Complete Response to an Anti–Type I Insulin-like Growth Factor Receptor Regimen in Patients with Breast Cancer

Article

作者: Julia D. Wulfkuhle ; Gillian L. Hirst ; Rosa I. Gallagher ; for the I-SPY2 Trial Consortium ; Laura van’t Veer ; Lamorna Brown-Swigart ; Laura J. Esserman ; Emmanuel F. Petricoin ; Denise M. Wolf ; Christina Yau ; Douglas Yee

Abstract:

Purpose::

Pretreatment specimens from patients treated on the I-SPY2 neoadjuvant breast cancer trial were studied to identify prespecified biomarkers associated with response to the regimen of paclitaxel, the anti–type I insulin-like growth factor receptor (IGF-1R) antibody ganitumab, and metformin (PGM) followed by doxorubicin and cyclophosphamide (AC) compared with control therapy (paclitaxel followed by AC). The primary endpoint of this trial is pathologic complete response (pCR).

Experimental Design::

One hundred six patients treated with PGM and 119 contemporary controls were evaluated using laser capture microdissection and reverse-phase protein array to evaluate 32 prespecified potential predictive biomarkers in the IGF-1R pathway and 109 additional exploratory endpoints.

Results::

Total levels of IGF-1R were poorly correlated with phosphorylated IGF-1R/insulin receptor (IR). Higher levels of phosphorylated IGF-1R/IR were associated with an increased likelihood of obtaining pCR, especially in the hormone receptor (HR)–positive subgroup. Markers of immune response also showed an association with pCR but differed between HR+ and HR− subgroups. In HR− tumors, phospho-STAT1 Y701 and low levels of phospho-p27 associated with pCR. These relationships were not observed in patients treated with control chemotherapy.

Conclusions::

Activation status of IGF-1R/IR associated with increased pCR to PGM in HR+ breast cancers. Immune activation markers were also associated with response in HR+ and HR− subgroups. Thus, IGF-1R may directly regulate tumor biology and associate with immune response to therapy.

2023-09-01·Clinical cancer research : an official journal of the American Association for Cancer Research

Phase I trial of Ganitumab plus Dasatinib to Cotarget the Insulin-Like Growth Factor 1 Receptor and Src Family Kinase YES in Rhabdomyosarcoma

Article

作者: Glod, John W. ; Akshintala, Srivandana ; Sundby, R. Taylor ; Palacio-Yance, Isabel ; Kaplan, Rosandra N. ; Dombi, Eva ; Miettinen, Markku M. ; Widemann, Brigitte C. ; Pan, Alexander ; Yohe, Marielle E. ; Steinberg, Seth M. ; Bernstein, Donna ; Navid, Fariba ; Derdak, Joanne ; Lei, Haiyan ; Heske, Christine M. ; Helman, Lee J. ; Chen, Helen X. ; Herrera, Kailey R. ; Mascarenhas, Leo ; Shern, Jack F. ; Gross, Andrea M.

Abstract:

Purpose::

Antibodies against insulin-like growth factor (IGF) type 1 receptor have shown meaningful but transient tumor responses in patients with rhabdomyosarcoma (RMS). The SRC family member YES has been shown to mediate IGF type 1 receptor (IGF-1R) antibody acquired resistance, and cotargeting IGF-1R and YES resulted in sustained responses in murine RMS models. We conducted a phase I trial of the anti–IGF-1R antibody ganitumab combined with dasatinib, a multi-kinase inhibitor targeting YES, in patients with RMS (NCT03041701).

Patients and Methods::

Patients with relapsed/refractory alveolar or embryonal RMS and measurable disease were eligible. All patients received ganitumab 18 mg/kg intravenously every 2 weeks. Dasatinib dose was 60 mg/m2/dose (max 100 mg) oral once daily [dose level (DL)1] or 60 mg/m2/dose (max 70 mg) twice daily (DL2). A 3+3 dose escalation design was used, and maximum tolerated dose (MTD) was determined on the basis of cycle 1 dose-limiting toxicities (DLT).

Results::

Thirteen eligible patients, median age 18 years (range 8–29) enrolled. Median number of prior systemic therapies was 3; all had received prior radiation. Of 11 toxicity-evaluable patients, 1/6 had a DLT at DL1 (diarrhea) and 2/5 had a DLT at DL2 (pneumonitis, hematuria) confirming DL1 as MTD. Of nine response-evaluable patients, one had a confirmed partial response for four cycles, and one had stable disease for six cycles. Genomic studies from cell-free DNA correlated with disease response.

Conclusions::

The combination of dasatinib 60 mg/m2/dose daily and ganitumab 18 mg/kg every 2 weeks was safe and tolerable. This combination had a disease control rate of 22% at 5 months.

2023-07-01·Cancer medicine

Phase 2 trial of palbociclib and ganitumab in patients with relapsed Ewing sarcoma

Article

作者: David S. Shulman ; Grace Fairchild ; Wendy B. London ; Priscilla Merriam ; Edwin Choy ; Kerri L. Cavanaugh ; Andrew Posner ; Kelly Klega ; Emma Barker ; Brian D. Crompton ; Steven G. DuBois ; Lillian M. Guenther ; Pei-Chi Kao ; Kimberly Stegmaier ; Ketki Bhushan

Abstract:

Background:

Ewing sarcoma (EWS) is an aggressive sarcoma with few treatment options for patients with relapsed disease. Cyclin‐dependent kinase 4 (CDK4) is a genomic vulnerability in EWS that is synergistic with IGF‐1R inhibition in preclinical studies. We present the results of a phase 2 study combining palbociclib (CDK4/6 inhibitor) with ganitumab (IGF‐1R monoclonal antibody) for patients with relapsed EWS.

Patients and Methods:

This open‐label, non‐randomized, phase 2 trial enrolled patients ≥12 years with relapsed EWS. All patients had molecular confirmation of EWS and RECIST measurable disease. Patients initially received palbociclib 125 mg orally on Days 1–21 and ganitumab 18 mg/kg intravenously on Days 1 and 15 of a 28‐day cycle. The primary endpoints were objective response (complete or partial) per RECIST and toxicity by CTCAE. An exact one‐stage design required ≥4 responders out of 15 to evaluate an alternative hypothesis of 40% response rate against a null of 10%. The study was closed following enrollment of the 10th patient due to discontinuation of ganitumab supply.

Results:

Ten evaluable patients enrolled [median age 25.7 years (range 12.3–40.1)]. The median duration of therapy was 2.5 months (range 0.9–10.8). There were no complete or partial responders. Three of 10 patients had stable disease for >4 cycles and 2 had stable disease at completion of planned therapy or study closure. Six‐month progression‐free survival was 30% (95% CI 1.6%–58.4%). Two patients had cycle 1 hematologic dose‐limiting toxicities (DLTs) triggering palbociclib dose reduction to 100 mg daily for 21 days. Two subsequent patients had cycle 1 hematologic DLTs at the reduced dose. Eighty percent of patients had grade 3/4 AEs, including neutropenia (n = 8), white blood cell decreased (n = 7), and thrombocytopenia (n = 5). Serum total IGF‐1 significantly increased (p = 0.013) and ctDNA decreased during the first cycle.

Conclusions:

This combination lacks adequate therapeutic activity for further study, though a subset of patients had prolonged stable disease.

项与盖尼塔单抗相关的新闻（医药）

2026-08-07

·NEJM医学前沿

我们年初请专家梳理的2026肺癌研究，3项已登上顶刊

今年1月，上海市胸科医院韩宝惠、钟华教授团队应《NEJM医学前沿》编辑部邀请，展望2026年值得关注的肺癌研究，重点梳理小细胞肺癌双特异性连接器、晚期非小细胞肺癌双抗与抗体药物偶联物、EGFR第20外显子插入突变以及HER2突变NSCLC精准治疗等五大方向。截至7月底，文中提及的10项3期试验中的5项结果已经公布，包括《新英格兰医学杂志》（NEJM）发表的WU-KONG28研究以及《柳叶刀》（The Lancet）发表的HARMONi-6和OptiTROP-Lung05研究。我们在此首次发表这篇2026年肺癌临床研究格局展望。为方便读者阅读，我们在原文以编者注形式简介已发表结果。从年初展望到年中兑现： 2026肺癌临床研究进入收获期张波，韩宝惠*，钟华上海市胸科医院呼吸与危重症医学科；上海交通大学医学院附属胸科医院呼吸与危重症医学科 *通讯作者 2025年，肺癌临床诊疗在失败与挫折中曲折前进。双特异性连接器、双特异性抗体、抗体药物偶联物（ADC）等新型治疗手段从概念验证逐步走向临床实践，并开始写入指南，正在改变既有治疗策略，为患者提供新的内科治疗选择。2026年，更多循证证据有望进一步推动肺癌临床治疗策略优化。本文将盘点2026年值得关注的5大领域及其代表性临床研究。未来已来，双特异性连接器在小细胞肺癌中的深入研究小细胞肺癌是恶性程度最高的肺癌病理亚型，尤其是广泛期小细胞肺癌患者，预后较差，中位生存时间仅为10~12个月[1-2]。既往包括大分子抗血管生成药物[3]、新型化疗药物[4-5]、新靶点药物[6]、PARP抑制剂[7]等多种不同作用机制的药物，均曾被探索用于广泛期小细胞肺癌治疗，但相关研究均未能获得足以支持适应证获批的结果。因此，在很长一段时间内，含铂双药化疗是广泛期小细胞肺癌唯一的一线治疗选择。虽然针对PD-1/PD-L的免疫检查点抑制剂已获批临床应用，但其带来的获益十分有限，患者中位生存时间仅为12~15个月[8-10]。因此，小细胞肺癌，尤其是广泛期小细胞肺癌的内科治疗，仍代表肺癌临床诊疗领域巨大的未被满足的临床需求。双特异性连接器的出现，有望进一步改善患者生存（点击阅读）。现有双特异性连接器主要通过肿瘤细胞表面表达的DLL-3蛋白（delta-like ligand 3）锚定肿瘤细胞，另一端则通过CD3结合T淋巴细胞，从而使淋巴细胞在肿瘤病灶附近富集，并通过释放颗粒酶、穿孔素等效应分子杀伤肿瘤细胞。在早期概念验证阶段，双特异性连接器已在难治性小细胞肺癌患者中展示了非常有前景的疗效及可管理的安全性(点击阅读)。一项2期临床试验纳入220例晚期小细胞肺癌患者[11]，这些患者既往中位治疗线数为2线，接受推荐剂量的塔拉妥单抗（tarlatamab，一种针对DLL-3的双特异性连接器）治疗后，客观缓解率（ORR）为40%，中位无进展生存期（PFS）4.9个月，9个月总生存（OS）率达68%。基于前期研究数据，双特异性连接器在广泛期小细胞肺癌一线治疗、维持治疗、后线治疗等领域的临床开发迅速推进。其中，塔拉妥单抗二线治疗的数据已经于2025年发表[12]。在这项国际多中心、开放标签、随机对照3期临床试验中，研究者纳入接受含铂双药治疗后出现疾病进展的广泛期小细胞肺癌患者，符合入组标准的患者，按1:1的比例随机接受tarlatamab或化疗。结果显示，塔拉妥单抗和化疗组的中位OS分别为13.6个月和8.3个月；中位PFS分别为4.2个月和3.7个月；ORR分别为35%和20%，中位缓解持续时间分别为6.9个月和5.5个月。目前，塔拉妥单抗在一线（DeLLphi-312）和维持治疗（DeLLphi-305，NCT06211036）均已有3期随机对照临床试验开展。根据ClinicalTrials.gov公开注册信息，DeLLphi-305研究已经完成入组并有望在2026年公布研究数据。考虑到塔拉妥单抗在二线治疗的成功以及1b期临床试验中所表现出的与免疫治疗的协同作用[13]，该研究结果值得期待。若研究取得成功，可能重塑当前标准治疗格局。未来几年，DLL-3仍将是小细胞肺癌药物研发的核心靶点。围绕这一靶点，ADC及双特异性连接器是两大重要布局方向。考虑到第一款针对DLL-3的ADC早在10年前即宣告失败[14]，同时其递送化疗药物的属性可能使其与一线含铂双药联合应用时面临毒性叠加等潜在限制，因此，双特异性连接器可能更具发展前景。实际上，从2025年各大会议公布的数据看，双特异性连接器已经在小细胞肺癌掀起研究热潮，并可能在未来几年持续保持研究热度。alveltamig（ZG006）[15]、gocatamig [16]、obrixtamig [17]等药物均已公布早期概念验证数据，支持进一步研发；其中部分双特异性连接器还可以针对DLL3的不同表位。整体而言，双特异性连接器是未来几年小细胞肺癌领域的重要研究方向。我们预计多款产品将陆续公布相关研究结果，而塔拉妥单抗作为这一领域进展最快的产品，其研究数据及研发策略具有重要参考意义。大潮将起：下一代免疫疗法的曙光 ——双特异性抗体免疫检查点抑制剂的加入为驱动基因突变阴性晚期非小细胞肺癌（NSCLC）患者的治疗带来了革命性变化，将患者OS从12~15个月延长至25个月左右[18]。然而，这部分患者目前仍面临疗效“瓶颈”。如何进一步提高疗效，是近年来学术界探索的热点问题之一。双特异性抗体（双抗）有望迭代在晚期NSCLC患者中已建立的以PD-1/PD-L1为基础的治疗体系，并进一步延长患者生存时间。双抗是一类经过工程化设计的创新抗体药物，能够同时特异性结合两种不同抗原或同一抗原的两个不同表位。这种独特设计突破了传统单克隆抗体“一种抗体，一个靶点”的局限性，赋予药物多重作用机制和较大的治疗潜力[19]。以依沃西单抗（ivonescimab）为代表的此类药物，已经开始逐渐改变临床治疗结局。 2025年，Lancet率先发表了依沃西单抗与帕博利珠单抗头对头比较的3期随机对照临床试验数据（HARMONi-2研究）[20]。该项研究纳入驱动基因突变阴性且PD-L1阳性表达的晚期NSCLC患者，比较两种药物一线治疗的疗效与安全性。结果显示，与帕博利珠单抗单药5.8个月的中位PFS相比，依沃西单抗组的中位PFS延长至11.1个月；两组3级及以上治疗相关不良事件发生率分别为29%和16%。随后，Lancet又发表了聚焦全人群的HARMONi-6研究结果[21]。在未经PD-L1选择的人群中，替雷利珠单抗联合化疗的中位PFS为6.9个月，而依沃西单抗联合化疗组的中位PFS为11.1个月。从现有数据看，针对PD-1和VEGF的双抗展示了良好的应用前景，但仍有两个关键问题缺乏充分循证证据支持。第一，PFS获益能否最终转化为OS获益。OS是评价药物疗效的“金标准”。对于免疫治疗而言，其延迟应答及生存曲线的“长拖尾”现象，OS结果尤为重要。遗憾的是，目前双抗类药物在驱动基因突变阴性晚期NSCLC患者的一线治疗中，尚无OS数据公布。从研发进度看，HARMONi-2研究和HARMONi-6研究有可能2026年公布最终的OS数据，如果两组生存曲线明显分离，且OS差异具有临床意义，将为同类药物研发提供重要参考（编者注：2026年6月7日，HARMONi-6试验OS数据公布，依沃西单抗联合化疗组的中位OS为27.9个月，替雷利珠单抗联合化疗的中位OS为23.7个月[HR，0.66；95% CI，0.50~0.87；P单侧＜0.0017，符合预设界值]）[22]。第二，多种族人群的外部验证数据缺乏。HARMONi-2研究和HARMONi-6研究主要基于中国人群开展，相关结果能否在更广泛人群中重复仍有待明确。目前，纳入更多种族人群的国际多中心临床研究HARMONi-3（NCT05899608）有望于2026年公布首次分析数据。该研究将PFS和OS设定为共同主要研究终点，将为OS获益提供统计学层面的确定性结论。随着第一款双特异性抗体取得成功，越来越多类似药物进入到肺癌，包括小细胞肺癌的研发赛道。双特异性抗体同样是未来几年肺癌领域的研发热点。pumitamig（NCT07361510）和SSGJ-707（NCT06980272）已在PD-L1阳性晚期NSCLC一线治疗中开展3期随机对照试验；PM8002（NCT05879068）目前注册研究为联合化疗二线治疗SCLC的2期单臂试验；IMM2510 （NCT06746870）则为联合化疗一线治疗NSCLC或三阴性乳腺癌的2期试验。若相关研究取得阳性结果，有望对当前以PD-1/PD-L1抑制剂为基础的治疗策略形成全面的升级和迭代。蓄锐待时：ADC的一线应用 ADC是一个具有较长发展历史的治疗概念，借助可以特异性锚定于肿瘤细胞表面的抗体，将细胞毒类药物精准递送至肿瘤细胞，从而实现生物药的“精准结合”与化疗药的“强力杀伤”（点击阅读）。在肺癌领域，ADC的研发并非一帆风顺。由于毒性等原因，很长一段时间并无ADC获批在临床应用。随着偶联技术、细胞毒性载荷优化及靶点识别等技术的进步，ADC类药物的毒性、稳定性及精准性均得到进一步改善，使其在临床应用，尤其是在驱动基因突变阴性的晚期NSCLC患者中的应用成为可能。目前，驱动基因突变阴性晚期NSCLC患者的标准治疗策略主要基于PD-L1表达水平：PD-L1≥50%可以接受免疫单药治疗[23]；PD-L11%~49%的患者可以接受免疫单药或免疫联合含铂双药化疗[24]；PD-L1＜1%的患者需要免疫治疗联合含铂双药化疗[25-26]。“疗效瓶颈”是目前这类患者遇到的普遍问题。除了以双特异性抗体替代PD-1/PD-L1抑制剂外，另一个重要研究方向是以ADC类药物替代含铂双药化疗。目前，针对TROP-2的ADC类药物研究最为深入。芦康沙妥珠是一款针对TROP-2的ADC [27]，其偶联的细胞毒性载荷为I型DNA拓扑异构酶抑制剂，抗体药物比值为7.4。一项3期随机对照临床试验纳入携带EGFR敏感突变且第三代靶向药物耐药的晚期NSCLC患者[28]，入组患者分别接受芦康沙妥珠单药与含铂双药化疗。结果显示，芦康沙妥珠单抗较含铂双药化疗显示出更好的疗效，且安全性相似。两组中位PFS分别为8.3个月和4.3个月；中位OS分别为未达到和17.4个月。一项双队列2期临床试验则探索了芦康沙妥珠单抗联合tagitanlimab（一款PD-L1免疫检查点抑制剂）的疗效及安全性[29]。研究根据给药剂量及给药间隔将患者分为两个队列：队列1给予芦康沙妥珠单抗5 mg/kg，联合tagitanlimab 1200 mg，每3周一次；队列2给予芦康沙妥珠单抗5 mg/kg，联合tagitanlimab 1200 mg，每2周一次。两组ORR分别为40.0%和66.7%，DCR分别为85.0%和92.1% ，中位PFS分别为15.4个月和未达到，疗效数值明显高于当前标准治疗的数据。目前，多项3期随机对照临床试验已经开展并有望于2026年公布研究结果。这些研究包括： 1. 在PD-L1≥50%的患者中比较帕博利珠单抗单药±戈沙妥珠单抗的疗效及安全性（NCT05609968）（编者注：据国外媒体消息，该项研究期中分析显示，PFS尽管有获益趋势，但OS很难获益，故而试验已经停止，其结果将会在国际医学会议上公布）。 2. 芦康沙妥珠单抗联合帕博利珠单抗对比帕博利珠单抗一线治疗PD-L1阳性的局部晚期或转移性非小细胞肺癌患者的随机、开放性、多中心3期临床试验（编者注：2026年6月，OptiTROP-Lung05研究结果发表，在PD-L1阳性、无可靶向基因改变的晚期NSCLC一线治疗中，芦康沙妥珠联合帕博利珠单抗较帕博利珠单抗单药显著延长PFS[中位PFS未达到 vs. 5.7个月；HR，0.35；95% CI，0.26～0.47；P<0.0001]）[30]。 3. 芦康沙妥珠单抗或含铂双药化疗联合帕博利珠单抗一线治疗PD-L1阴性的晚期NSCLC患者的疗效及安全性（NCT06711900）（编者注：据科伦博泰官网信息，该项研究的期中分析显示，芦康沙妥珠单抗联合帕博利珠单抗疗法与帕博利珠单抗联合培美曲塞及铂类化疗相比在PFS方面显示出统计学意义和临床意义的显著改善，OS方面亦观察到获益趋势）。上述研究的阳性结果，有望替代当前的标准治疗策略。绝处逢生： EGFR第20外显子插入突变用 EGFR第20外显子插入突变是仅次于EGFR第19外显子缺失突变和21外显子L858R突变的第三大突变类型[31]。该突变的空间位阻效应导致现有TKI类药物无法与靶点有效结合；目前已获批的第一代、第二代及第三代EGFR-TKI对此类突变的客观缓解率较低（0%~9%）。长期以来，以铂类药物为基础的化疗是这部分患者的一线标准治疗，但OS较差，仅有16个月左右[32]。目前，围绕该靶点的药物研发主要聚焦在3个方向：双特异性抗体、特异性靶向药物及第三代EGFR-TKI加量。双特异性抗体：埃万妥单抗是一款人源化EGFR-MET双特异性抗体，可通过结合受体胞外段区域，促进受体-抗体复合物降解。基于1期临床试验（CHRYSALIS，NCT02609776）中观察到的40% ORR，11.1个月中位缓解持续时间和8.3个月中位PFS，该药获得美国食品药品管理局（FDA）的附条件批准上市[33]。随后，在一项全球多中心3期临床试验（PAPILLON）中[34]，埃万妥单抗显示出优于标准治疗的疗效。经独立审评委员会评估，两组中位PFS分别为11.4个月和6.7个月，ORR分别为73%和47%。PAPILLON研究是首个在一线治疗中获得阳性结果的3期随机对照临床试验，但其PFS能否转化为OS获益尚不明确。首次数据公布时，两组中位OS分别为未达到和24.4个月。考虑到研究允许交叉，一线应用带来的OS获益可能会被稀释；若后续研究能证实OS获益，将为该药的一线优先应用提供充分依据。特异性靶向药物：特异性靶向药物在这部分患者中的研究经历了较大的波折。早期，波奇替尼展示了一定的抗肿瘤活性，ORR和中位PFS分别为22.7%和5.6个月，但该药不良反应较重，尤其是严重皮疹、腹泻等不良反应的发生，对患者生活质量造成严重影响[35]。临床研究中，因不良反应导致治疗中断及剂量降低的患者比例分别达89%和76%，皮疹发生率达50%，该药最终未能上市。另一款药物莫博赛替尼则经历了上市后退市。在一项1/2期临床试验中[36]，莫博赛替尼后线治疗这部分患者的ORR、DCR、中位PFS和中位OS分别为28%、78%、7.3个月和24个月。莫博赛替尼曾被附条件批准治疗携带EGFR第20外显子插入突变的患者，但在一线随机对照临床试验中，该药遭遇“滑铁卢”。3期随机对照临床试验显示[37]，一线接受莫博赛替尼或含铂双药化疗的中位PFS均为9.6个月（HR，1.04；P=0.803），ORR分别为32%和30%。另一款药物舒沃替尼后线治疗这部分患者的ORR为60.8%，展示出良好的抗肿瘤活性，估计中位PFS为9.7个月[38]。目前这一类药物尚无任何3期随机对照临床试验研究得到阳性结果。一项国际、多中心、3期临床试验（NCT05668988，WU-KONG28）目前正在进行，公开资料显示研究已经完成入组，有望于2026年公布结果。考虑到该药在2期临床试验中，展示了远优于当前标准治疗的疗效，因此3期临床试验有望获得阳性结果。如研究得到积极结果，将会对这部分患者的一线治疗格局带来重大影响（编者注：WU-KONG28试验结果于2026年5月底在《新英格兰医学杂志》在线发表 [39]。研究结果显示，与标准含铂双药化疗相比，舒沃替尼一线治疗显著延长无进展生存期[10.3个月 vs. 7.5个月；HR，0.65；95% CI，0.50~0.85；P<0.001]。OS数据成熟度为38.9%。两组中位OS分别为29.8个月和28.8个月，HR为0.99）。第三代EGFR-TKI加量：早期小样本回顾性临床研究发现，三代EGFR-TKI药物加量可能是克服这一靶点的潜在治疗策略[40]。一项纳入25例患者的前瞻性临床研究发现，接受160 mg奥希替尼治疗患者的ORR和中位PFS分别为28%和6.8个月[40]。一项1b期临床试验探索了不同剂量伏美替尼（一款第三代EGFR-TKI）治疗EGFR第20外显子插入突变的疗效及安全性（FAVOUR研究）[41]。初治且接受240 mg每日一次口服治疗的患者、经治且接受240 mg每日一次口服治疗的患者，以及经治且接受160 mg每日一次口服治疗的患者，ORR分别为78.6%、46.2%和38.5%。加量治疗并未显著增加不良反应。治疗相关3级以上不良事件发生率分别为13%、29%和18%。随后的2期单臂临床试验确认了上述发现：71例经治患者接受240 mg伏美替尼治疗，ORR为51.4%，中位PFS为8.3个月。目前，伏美替尼一线对比含铂双药化疗的3期随机对照临床试验正在进行中（FURVENT，NCT05607550）。公开资料显示，研究目前已经完成入组，有望于2026年公布结果，数据值得期待。精准破局：HER2突变 NSCLC患者的精准治疗 HER2基因作为驱动突变发现较早，且在乳腺癌中已围绕该靶点建立了完善的诊疗体系[42]；但在NSCLC领域，针对该靶点的治疗在很长一段时间内始终未能取得实质性突破。T-DM1等ADC曾一度被指南纳入[43]，并作为低级别推荐，但始终未能获批适应证。泛HER2抑制剂（如吡咯替尼）后线治疗这部分患者的ORR为30%，中位PFS为6.9个月，并在与阿帕替尼联合治疗中显示出良好抗肿瘤活性[44-46]；但由于缺乏注册性研究数据，最终同样未能获批适应证。目前，已经有两款ADC类药物获批用于治疗携带HER2突变的晚期NSCLC患者[47-48]，其抗肿瘤活性与疾病控制时间较当前标准治疗均有明显提升。然而，ADC普遍存在的安全性问题，尤其是血液学毒性，可能会限制其临床应用。两款靶向治疗药物——zongertinib和sevabertinib [49-52]，有望为这部分患者提供高效、低毒的治疗选择，从而真正将这部分患者带入“精准治疗”时代，开辟新的肺癌治疗赛道。欧洲肿瘤内科学会（ESMO）2025年会公布了zongertinib单药一线治疗携带HER2酪氨酸激酶域突变的晚期NSCLC患者的疗效及安全性。74例患者的ORR和DCR分别为77%和96%，6个月的PFS率为79%，3级及以上治疗相关不良事件发生率仅为18%，且未出现4~5级治疗相关不良事件，仅9%的患者因不良事件而导致治疗终止。在另外一款靶向药物sevabertinib的研究中，接受非HER2靶向治疗、接受过HER2 ADC治疗以及初治患者分别有81例、55例和73例，其ORR分别为52%、21%和71%，中位PFS分别为8.3个月、5.5个月和未达到。3级及以上治疗相关不良事件发生率分别为36%、31%和21%。上述研究数据为HER2突变转移性NSCLC患者的治疗提供了精准、高效的内科选择，无论是疗效还是安全性均具有明显优势。目前，以当前标准治疗为阳性对照的全球随机3期临床试验（NCT06452277，SOHO-02；Beamion LUNG 2，NCT06151574）正在进行。两项研究分别比较sevabertinib或zongertinib与标准策略一线治疗HER2突变晚期NSCLC的疗效和安全性，其结果将进一步明确HER2选择性TKI在一线治疗中的地位。总结 “双抗”与“ADC”有望成为2026年肺癌领域各大学术会议的主旋律。以双抗及ADC为基础的新型治疗策略，可能为晚期NSCLC患者，尤其是驱动基因突变阴性患者建立新的一线治疗策略，缓解目前这部分患者遇到的“疗效瓶颈”问题。目前，双抗已经展示出较PD-1/PD-L1抑制剂更优的PFS，ADC联合免疫治疗也已在PD-L1阳性晚期NSCLC一线治疗中显示出明确PFS获益。未来，双抗与ADC组合的疗效值得期待。围绕EGFR、ALK这两大肺癌领域的重要通路，短期内第四代药物上市并替代当前标准治疗的可能性不大；因此，EGFR第20外显子插入突变、HER2突变等少见突变逐渐引起学术界重视，并有望在2026年迎来全新治疗突破。随着治疗技术进步，小细胞肺癌这一既往被视为药物研发“死亡之谷”的难治性肿瘤，也开始逐渐迎来新希望，双特异性连接器的出现，为患者一线治疗带来疗效的提升。随着人工智能技术逐渐贯穿于药物研发各个阶段，从靶点发现到后续化合物合成、筛选、优化及临床试验执行等，均较传统研发周期有缩短。在国家宏观政策支持下，未来生物制药领域将大有所为。参考文献 1. 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A randomized phase II study of LY2510924 and carboplatin/etoposide versus carboplatin/etoposide in extensive-disease small cell lung cancer. Lung Cancer 2017;105:7-13. 6. Glisson B, Besse B, Dols MC, et al. A randomized, placebo-controlled, phase 1b/2 study of rilotumumab or ganitumab in combination with platinum-based chemotherapy as first-line treatment for extensive-stage small-cell lung cancer. Clin Lung Cancer 2017;18:615-25.e8. 7. Ai X, Pan Y, Shi J, et al. Efficacy and safety of niraparib as maintenance treatment in patients with extensive-stage SCLC after first-line chemotherapy: A randomized, double-blind, phase 3 study. J Thorac Oncol 2021;16:1403-14. 8. Goldman JW, Dvorkin M, Chen Y, et al. Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2021;22:51-65. 9. Horn L, Mansfield AS, Szczęsna A, et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med 2018;379:2220-9. 10. Wang J, Zhou C, Yao W, et al. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2022;23:739-47. 11. Ahn MJ, Cho BC, Felip E, et al. Tarlatamab for patients with previously treated small-cell lung cancer. N Engl J Med 2023;389:2063-75. 12. Mountzios G, Sun L, Cho BC, et al. Tarlatamab in small-cell lung cancer after platinum-based chemotherapy. N Engl J Med 2025;393:349-61. 13. Paulson KG, Lau SCM, Ahn MJ, et al. Safety and activity of tarlatamab in combination with a PD-L1 inhibitor as first-line maintenance therapy after chemo-immunotherapy in patients with extensive-stage small-cell lung cancer (DeLLphi-303): a multicentre, non-randomised, phase 1b study. Lancet Oncol 2025;26:1300-11. 14. Uprety D, Remon J, Adjei AA, et al. All that glitters is not gold: The story of rovalpituzumab tesirine in SCLC. J Thorac Oncol 2021;16:1429-33. 15. Ai XH, Zhang YY, Zhang TM, et al. A phase 2 dose expansion study of ZG006, a trispecific T cell engager targeting CD3/DLL3/DLL3, as monotherapy in patients with advanced small cell lung cancer. J Clin Oncol 2025;43: suppl.8007. 16. Beltran H, Johnson M, Jain P, et al. 2758MO Updated results from a phase I/II study of gocatamig for small cell lung cancer (SCLC) and other neuroendocrine cancers. Ann Oncol 2025;36:S1367. 17. Peters S, Dziadziuszko R, Kalinka E, et al. 2759MO DAREON®-8: A phase I trial of first-line obrixtamig plus chemotherapy and atezolizumab in extensive-stage small cell lung carcinoma (ES-SCLC). Ann Oncol 2025;36:S1367-S1368. 18. Li Z, Wang T, Liu J, et al. The mechanism and research progress of PD-1/PD-L1 on immune escape of lung cancer. Transl Cancer Res 2025;14:6041-51. 19. Bai Y, Lei H, Gou S, et al. Bispecific antibody-drug conjugates: a modular blueprint for next-generation cancer therapeutics. Arch Pharm Res 2026;49:61-100. 20. Xiong A, Wang L, Chen J, et al. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet 2025;405:839-49. 21. Chen Z, Yang F, Jiang Z, et al. Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial. Lancet 2025;406:2078-88. 22. Lu S, Liu B, Luo Y, et al. Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China. Lancet 2026;407:2620-9. 23. Reck M, Rodríguez-Abreu D, Robinson AG,et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016;375:1823-33. 24. Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet 2019;393:1819-30. 25. Paz-Ares L, Luft A, Vicente D, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 2018;379:2040-51. 26. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 2018;378:2078-92. 27. Zhou YQQ, Huang WN, Hang XY, et al. Inhibiting TROP2 in advanced non-small-cell lung cancer with sacituzumab govitecan, datopotamab deruxtecan, and sacituzumab tirumotecan: similarities and differences. Cancer Chemother Pharmacol 2025;95:106. 28. Fang W, Wu L, Meng Xet al. Sacituzumab tirumotecan in EGFR-TKI-resistant, EGFR-mutated advanced NSCLC. N Engl J Med 2026;394:13-26. 29. Hong S, Wang Q, Cheng Y, et al. First-line sacituzumab tirumotecan with tagitanlimab in advanced non-small-cell lung cancer: a phase 2 trial. Nat Med 2025;31:3654-61. 30. Xiong A, Yao W, Zheng W, et al. Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial. Lancet 2026;407:2607-19. 31. Remon J, Hendriks LEL, Cardona Af, et al. EGFR exon 20 insertions in advanced non-small cell lung cancer: A new history begins. Cancer Treat Rev 2020:90:102105. 32. Wu JY, Yu CJ, Shih JY. Effectiveness of treatments for advanced non-small-cell lung cancer with exon 20 insertion epidermal growth factor receptor mutations. Clin Lung Cancer 2019;20:e620-e630. 33. Park K, Haura EB, Leighl NB, et al. Amivantamab in EGFR exon 20 insertion-mutated non-small-cell lung cancer progressing on platinum chemotherapy: Initial results from the CHRYSALIS phase I study. J Clin Oncol 2021;39:3391-402. 34. Zhou C, Tang KJ, Cho BC, et al. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions. N Engl J Med 2023;389:2039-51. 35. Cornelissen R, Prelaj A, Sun S, et al. Poziotinib in treatment-naive NSCLC harboring HER2 exon 20 mutations: ZENITH20-4, a multicenter, multicohort, open-label, phase 2 trial (Cohort 4). J Thorac Oncol 2023;18:1031-41. 36. Zhou CC, Ramalingam SS, Kim TM, et al. Treatment outcomes and safety of mobocertinib in platinum-pretreated patients with EGFR exon 20 insertion-positive metastatic non-small cell lung cancer: A phase 1/2 open-label nonrandomized clinical trial. JAMA Oncol 2021;7:e214761. 37. Jänne PA, Wang BC, Cho BC, et al. First-line mobocertinib versus platinum-based chemotherapy in patients with EGFR exon 20 insertion-positive metastatic non–small-cell lung cancer in the phase III EXCLAIM-2 trial. J Clin Oncol 2025;43:1553-63. 38. Wang M, Fan Y, Sun M, et al. Sunvozertinib for patients in China with platinum-pretreated locally advanced or metastatic non-small-cell lung cancer and EGFR exon 20 insertion mutation (WU-KONG6): single-arm, open-label, multicentre, phase 2 trial. Lancet Respir Med 2024;12:217-24. 39. Zhou C, Greillier L, Liu G, et al. First-line sunvozertinib in NSCLC with EGFR exon 20 insertion mutations. N Engl J Med 2026 May 29 (Epub ahead of print). DOI: 10.1056/NEJMoa2604461. 40. Zwierenga F, van Veggel B, Hendriks LEL, et al. High-dose osimertinib in patients with advanced-stage EGFR exon 20 mutation-positive NSCLC: results from the phase 2 multicenter POSITION20 trial. Lung Cancer 2022;170:133-40. 41. Han B, Zhou C, Zheng W, et al. OA03.04 A Phase 1b Study Of Furmonertinib, an Oral, Brain Penetrant, Selective EGFR Inhibitor, in Patients with Advanced NSCLC with EGFR Exon 20 Insertions. J Thorac Oncol 2023;18:S49. 42. Fernandes CL, Silva DJ, Mesquita A. Novel HER2-targeted therapies in breast cancer. Cancers (Basel) 2024;16:87. 43. Li BT, Shen R, Buonocore D, et al. Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: results from a phase II basket trial. J Clin Oncol 2018;36:2532-7. 44. Yang G, Xu H, Yang Y, et al. Pyrotinib combined with apatinib for targeting metastatic non-small-cell lung cancer with HER2 alterations: a prospective, open-label, single-arm phase 2 study (PATHER2). BMC Med 2022;20:277. 45. Song Z, Lv D, Chen SQ, et al. Pyrotinib in patients with HER2-amplified advanced non-small-cell lung cancer: a prospective, multicenter, single-arm trial. Clin Cancer Res 2022;28:461-7. 46. Zhou C, Li X, Wang Q, et al. Pyrotinib in HER2-mutant advanced lung adenocarcinoma after platinum-based chemotherapy: a multicenter, open-label, single-arm, phase II study. J Clin Oncol 2020;38:2753-61. 47. Li ZM, Wang Y, Sun YP, et al. Trastuzumab rezetecan, a HER2-directed antibody–drug conjugate, in patients with advanced HER2-mutant non-small-cell lung cancer (HORIZON-Lung): phase 2 results from a multicentre, single-arm study. Lancet Oncol 2025;26:437-46. 48. Goto K, Goto Y, Kubo T, et al. Trastuzumab deruxtecan in patients with HER2-mutant metastatic non–small-cell lung cancer: primary results from the randomized, phase II DESTINY-Lung02 trial. J Clin Oncol 2023;41:4852-63. 49. Heymach JV, Ruiter G, Ahn MJ, et al. Zongertinib in previously treated HER2-mutant non–small-cell lung cancer. N Engl J Med 2025;392:2321-33. 50. Heymach JV, Opdam F, Barve M, et al. HER2-selective tyrosine kinase inhibitor zongertinib (BI 1810631) in patients with advanced or metastatic solid tumors with HER2 alterations: a phase Ia dose-escalation study. J Clin Oncol 2025;43:1337-47. 51. Le X, Kim TM, Loong HH, et al. Sevabertinib in advanced HER2-mutant non–small-cell lung cancer. N Engl J Med 2025;393:1819-32. 52. Siegel F, Siegel S, Kotýnková K, et al. Sevabertinib, a reversible HER2 inhibitor with activity in lung cancer. Cancer Discov 2026;16:81-94. 作者简介韩宝惠，教授，主任医师，博士生导师。上海市胸科医院呼吸与危重症医学科名誉主任；上海市领军人才，上海市优秀学科带头人；国务院特殊津贴获得者；中国呼吸医师奖获得者；曾获中华医学科技奖二等奖、上海市医学科技奖二、三等奖、中国呼吸医师奖、2022年度中国医疗产业创新一等奖（奇璞奖）、中国医药学会科技创新一等奖等多项殊荣；领衔承担国家十一五科技攻关项目、科技部重点专项等多项高水平重大、重点科研课题；在国内外高水平杂志发表肺癌领域专业论文300余篇，主编、参编医学专著10余部；现兼任中华肺癌学院执行院长、CSCO非小细胞肺癌专委会副主任委员、上海市医学会肿瘤靶分子专委会主委等职。钟华，教授，主任医师，博士生导师。上海市胸科医院呼吸与危重症医学科行政主任，国家自然科学基金评审专家，中华医学会生物免疫学会理事会理事，CSCO非小细胞肺癌委员，上海市抗癌协会第八届理事会理事，上海市医学会肿瘤靶向分子专科分会委员兼秘书，以美国匹兹堡大学访问学者身份从事肺癌免疫治疗的基础研究和转化研究，主持国家自然科学基金3项，上海市科委课题4项，国家科技部重点专项子课题1项，市级医院新兴前沿技术联合攻关项目1项，曾获中华医学科技奖/二等奖、上海市抗癌科技奖、上海交通大学医学院“研究型医师奖”等奖项。张波，上海交通大学医学院内科学博士，上海市胸科医院呼吸内科医师；BMC Medicine (IF：8.3)杂志Editor；《中华医学会肺癌临床诊疗指南(2024-2026版)》学术秘书；CSCO血管靶向专委会委员；上海市医学会循证医学专委会青委；以第一作者身份在Nature Communications、Cancer等杂志发表SCI收录论文20余篇；在JAMA Oncology发表comment、viewpoint等文章3篇；获得上海市卫健委、上海市“雏鹰计划”等资助；参与科技部重大专项一项；创建公众号《肿瘤论坛》。版权信息本文由《NEJM医学前沿》编辑部负责翻译、编写或约稿。对于源自NEJM集团旗下英文产品的翻译和编写文章，内容请以英文原版为准。中译全文以及所含图表等，由马萨诸塞州医学会NEJM集团独家授权。如需转载，请联系nejmqianyan@nejmqianyan.cn。未经授权的翻译是侵权行为，版权方保留追究法律责任的权利。点击下方名片，关注《NEJM医学前沿》

2023-12-14

·Business Wire

Insulin-Like Growth Factor Immunotherapy Advances: Crucial Findings on IGF-1R-Inhibiting Therapies Unveiled in Latest Research Publication - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "IGF-1R- and IGF-1 Targeted Immunotherapy Pipeline Review" report has been added to ResearchAndMarkets.com's offering. This research explores the current landscape of immunotherapy treatments targeting the insulin-like growth factor-1 receptor (IGF-1R), a significant player in oncological advancements. The detailed study delves into the intricate relationships between IGF-1R and various cancer types, offering valuable insights into the prospects and challenges of IGF-1R inhibitors and associated therapeutic approaches. IGF-1R Immunotherapy's Role Beyond Oncology The research publication also captures the significance of IGF-1R inhibition in conditions beyond cancer, particularly noting its overexpression in immune cells related to thyroid ophthalmopathy in Graves' disease. Understanding the role of IGF-1R can lead to enhanced therapeutic interventions aimed at mitigating inflammatory processes and improving symptoms in affected patients. This robust body of work encapsulates the critical developments in IGF-1R-targeted immunotherapy, offering a treasure trove of information to stakeholders in the biopharmaceutical industry, research institutions, healthcare professionals, and policy-makers. Expanding IGF-1R Inhibition Therapeutics: A Glimpse into the Future The document underscores the complexities and potential of targeting IGF-1 receptor pathways, thrusting readers to the forefront of immunotherapeutic innovation. The nuanced findings in our report are crucial for guiding future research directions, optimizing treatment regimens, and ultimately enhancing patient care within the realm of precision medicine. The discoveries and analyses presented in this publication not only illuminate the path for future scientific inquiries but also underpin the strategic decisions that will shape the next generation of IGF-1R-targeted therapies. The implications of the findings extend to translational research, clinical application, and the broader biotech industry's approach to disease treatment and patient well-being. For those committed to staying abreast of the latest breakthroughs in targeted immunotherapy, exploring the wealth of information housed within the pages of this research document is indispensable. Key Highlights and Innovations in IGF-1R Immunotherapy The document presents critical developments through a tabulated competitors' overview, covering essential details such as drug codes, targets or mechanisms of action, compound classes, territorial reach of key competitors, indications, and the current stages of research and development. An in-depth project history section, providing links to relevant sources of information, including press releases, company homepages, academic abstracts, presentations, and annual reports, further enriches the report's content. Insightful analysis of past and ongoing clinical trials, including the performance of monoclonal antibodies such as figitumumab, ganitumab, and dalotuzumab in various phases of testing, with special emphasis on phase III clinical outcomes. Exploration of cutting-edge strategies that leverage IGF-1R's cell-signaling dynamics for targeted drug delivery, such as the use of antibody-drug conjugates and radioimmunoconjugates. For more information about this report visit https://www.researchandmarkets.com/r/litbge About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

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2023-08-15

·PipelineReview

IGF-1R- and IGF-1 Targeted Immunotherapy Pipeline Review

BARCELONA, Spain I August 15, 2023 I La Merie Publishing released its newest product reviewing the pipeline of IGF-1R or IGF-1 targeted drugs or immunotherapy candidates: IGF-1R- and IGF-1 Targeted Immunotherapy Pipeline Review Target: Insulin-like growth factor-1 (IGF-1) & Receptor (IGF-1R Product Category: Antibody; Fusion Protein This product provides basic information on approved drugs and immunotherapy candidates in research and development targeting insulin-like growth factor-1 (IGF-1) or its receptor (IGF-1R). This product consists of: This product is delivered on the very same day of purchase by e-mail containing competitor and project history reports in pdf format and database credentials. Reports are prepared on the same day. IGF-1R is a key member of the insulin-like growth factor (IGF) axis, which involves in cancer development, metastasis and cancer therapeutic resistance. Anti-IGF-1R monoclonal antibody is among the first major therapeutic agents for IGF-1R inhibition. These antibodies inhibit the binding between IGF-1R and its ligands, thereby blocking the activation of IGF-1R homodimer and IGF-1R/InsR hybrid, but not the InsR homodimer. A number of fully human monoclonal antibodies, which target the α subunit of IGF-1R, have demonstrated anti-tumor activities in pre-clinical studies. After completion of early phase clinical trials, three of the IGF-1R antibodies (figitumumab, ganitumab, and dalotuzumab) were tested in phase III clinical trials. Another strategy is inhibiting the binding of IGF ligands to the receptor which can inactivate IGF-1R. Due to the lack of a clear clinical benefit in these phase III trials, further clinical research was not pursued. Meanwhile, several firms are taking advantage of elevated IGF-1 signaling in cancers to deliver therapeutic payloads directly to tumor tissue, e.g. by antibody-drug conjugates or radioimmunoconjugates. These drug programs exploit the fact that IGF-1R, upon binding to its ligand or an antibody, undergoes receptor-mediated endocytosis, resulting in internalization of any bound molecules. Off-target toxicity is minimized because IGF-1R activity is mostly limited to internal compartments of the cell in vital organs such as the heart, and only a few tissues in the bladder, prostate and endometrium show low to moderate surface expression of IGF-1R. IGF-1R is a transmembrane tyrosine kinase receptor that plays a role in development, metabolism, and immune regulation, and is overexpressed in orbital fibroblasts (OFs), B, and T cells of thyroid ophthalmopathy in Graves' disease. Blocking IGF-1(R) signalling reduces the expression of downstream inflammatory factors, thereby inhibiting the synthesis of hyaluronic acid and other glycosaminoglycan caused by OFs activation, as well as related inflammatory reactions including tissue congestion and edema; inhibit adipocyte cellularization of OFs, thereby reducing the disease activity of patients with active thyroid ophthalmopathy and improving proptosis, diplopia, ocular congestion and edema and other symptoms and signs. The report “ IGF-1R- and IGF-1 Targeted Immunotherapy Pipeline Review ” can be acquired at La Merie Publishing’s online store: https://lamerie.com/report/igf-1r-and-igf-1-targeted-immunotherapy-pipeline-review/ About La Merie Publishing La Merie Publishing is an independent business information provider for the biotechnology and pharmaceutical industry. La Merie Publishing prepares brief and full reports. La Merie Publishing products can be purchased in the online store www.lamerie.com and from selected Resellers. La Merie Publishing offers the service of custom report preparation for corporate clients, including, but not limited to, pipeline analysis reports, drug profiles and any other competitive intelligence elaboration of interest. SOURCE: La Merie Publishing

免疫疗法临床3期临床结果

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KEGG	Wiki	ATC	Drug Bank
D09908	盖尼塔单抗	-	DB12205

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适应症	最高研发状态	国家/地区	公司	日期
晚期癌症	临床3期	美国	ImmunityBio, Inc.	2011-04-07
晚期癌症	临床3期	美国	Takeda Pharmaceutical Co., Ltd.	2011-04-07
晚期癌症	临床3期	日本	Takeda Pharmaceutical Co., Ltd.	2011-04-07
晚期癌症	临床3期	日本	ImmunityBio, Inc.	2011-04-07
晚期癌症	临床3期	澳大利亚	Takeda Pharmaceutical Co., Ltd.	2011-04-07
晚期癌症	临床3期	澳大利亚	ImmunityBio, Inc.	2011-04-07
晚期癌症	临床3期	奥地利	ImmunityBio, Inc.	2011-04-07
晚期癌症	临床3期	奥地利	Takeda Pharmaceutical Co., Ltd.	2011-04-07
晚期癌症	临床3期	比利时	Takeda Pharmaceutical Co., Ltd.	2011-04-07
晚期癌症	临床3期	比利时	ImmunityBio, Inc.	2011-04-07

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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


NCT01318642 (CTgov)	临床2期	胰腺腺癌 \| 局部晚期胰腺腺癌	10	Placebo+Gemcitabine (Placebo + Gemcitabine)	鏇獵膚簾顧鏇壓廠遞蓋(淵糧壓簾製顧齋遞衊糧) = 廠膚鹹糧齋淵製壓構製鏇鏇夢觸獵鹽顧鬱憲艱 (壓鑰鹹積鹽積膚鏇簾憲, 製鏇艱鏇範憲簾獵網鹽 ~ 觸簾願鬱壓壓範繭壓糧) 更多	-	2024-11-08
				AMG 479+Gemcitabine (AMG 479 20 mg/kg + Gemcitabine)	鏇獵膚簾顧鏇壓廠遞蓋(淵糧壓簾製顧齋遞衊糧) = 壓壓觸積鬱鹽蓋製簾窪鏇鏇夢觸獵鹽顧鬱憲艱 (壓鑰鹹積鹽積膚鏇簾憲, 構鬱膚鏇餘鹹淵顧齋壓 ~ 觸繭鬱範觸夢衊鹹築網) 更多
NCT00630552 (QUILT-2.019, CTgov)	临床1/2期	胰腺腺癌 \| 转移性胰腺癌	138	AMG 655 (Phase 1b AMG 655 3mg/kg)	襯鏇壓膚窪壓構範餘鹹 = 繭醖顧構醖選壓獵範積鏇鏇鹽糧廠蓋鬱鹹齋築 (獵積醖築鏇遞網鹽網廠, 築簾簾蓋壓範襯簾遞餘 ~ 憲襯繭製顧廠壓醖夢願) 更多	-	2024-10-17
				AMG 655 (Phase 1b AMG 655 10mg/kg)	襯鏇壓膚窪壓構範餘鹹 = 襯壓齋願繭鹽夢膚鹽衊鏇鏇鹽糧廠蓋鬱鹹齋築 (獵積醖築鏇遞網鹽網廠, 築築壓齋鹹壓繭簾艱簾 ~ 鹽憲艱壓衊餘顧醖製窪) 更多
NCT00807612 (QUILT-2.017, CTgov)	临床1/2期	晚期鳞状非小细胞肺癌	15	AMG 479+Carboplatin+Paclitaxel (AMG 479 18 mg/kg + Paclitaxel/Carboplatin)	構壓鹹網窪遞遞繭築憲 = 積積鬱鑰憲鬱積觸憲衊製夢鏇膚選淵範鬱觸獵 (繭積網鏇獵積獵製範觸, 繭衊膚醖鏇鑰膚積繭築 ~ 襯蓋鏇鹹築遞蓋淵鑰鹽) 更多	-	2024-09-25
				Ganitumab+Carboplatin+Paclitaxel (Ganitumab 18 mg/kg + Paclitaxel/Carboplatin)	願觸艱觸鑰觸顧衊顧顧(淵製構襯壓夢餘願鑰製) = 廠顧齋蓋獵淵夢觸鏇糧選襯襯衊獵艱鹽獵鹹窪 (築鹹鬱鏇餘簾壓遞範鹽, 遞餘夢觸選鏇製齋繭範 ~ 衊構艱蓋衊選鹽鏇願鏇) 更多
NCT00626106 (QUILT-2.015, CTgov)	临床2期	转移性肿瘤 \| HR阳性乳腺癌	156	AMG 479 (Arm A: AMG 479 12 mg/kg IV Q2W + Endocrine Therapy)	積範餘繭繭願窪衊繭範(積餘夢醖遞衊餘糧壓糧) = 願糧築鬱醖蓋積廠積齋鏇鑰憲夢鑰網醖齋憲衊 (願築壓醖壓遞築淵範衊, 膚蓋窪積壓繭廠顧網齋 ~ 築鏇積網範廠糧齋壓選) 更多	-	2024-09-19
				Placebo (Arm B: Placebo IV Q2W + Endocrine Therapy)	積範餘繭繭願窪衊繭範(積餘夢醖遞衊餘糧壓糧) = 憲窪艱獵顧顧餘鑰艱顧鏇鑰憲夢鑰網醖齋憲衊 (願築壓醖壓遞築淵範衊, 襯鏇築膚衊繭製鹹網顧 ~ 獵襯鏇願襯艱遞積廠窪) 更多
NCT00791154 (SCLC, CTgov)	临床1/2期	广泛期小细胞肺癌	213	Ganitumab (Phase 2 Ganitumab)	獵夢願憲齋夢窪獵網觸(範衊鑰餘範齋網膚鬱獵) = 選齋鹹壓遞窪網選選蓋簾選膚壓鬱繭艱廠範齋 (簾築窪窪壓膚築夢蓋膚, 選遞鹹鏇遞願醖簾簾憲 ~ 醖鏇觸觸顧鏇繭襯獵艱) 更多	-	2024-08-23
				placebo+etoposide+carboplatin+cisplatin (Phase 2 Placebo)	獵夢願憲齋夢窪獵網觸(範衊鑰餘範齋網膚鬱獵) = 網衊膚觸網衊鏇鹹淵製簾選膚壓鬱繭艱廠範齋 (簾築窪窪壓膚築夢蓋膚, 醖膚製夢網衊鏇網廠膚 ~ 範壓選獵構築艱憲繭願) 更多
NCT00819169 (NCT00819169, CTgov)	临床1/2期	肉瘤 \| 卵巢癌 \| 转移性肿瘤 ... 更多	89	AMG 479+AMG 655 (Part 1 Cohort 1)	選齋繭範網獵夢鑰艱觸 = 齋選築鬱壓簾膚製製鹽壓築築壓壓糧廠鹹簾衊 (襯艱網膚窪製網襯窪構, 衊製夢顧簾醖餘餘廠顧 ~ 窪選顧糧積繭鹽餘製構) 更多	-	2024-08-20
				AMG 479+AMG 655 (Part 1 Cohort 2)	選齋繭範網獵夢鑰艱觸 = 構蓋窪鬱糧夢壓艱觸範壓築築壓壓糧廠鹹簾衊 (襯艱網膚窪製網襯窪構, 淵餘淵襯襯鹹積壓齋鏇 ~ 範鹹鏇願齋選襯廠艱繭) 更多
NCT04129151 (CTgov)	临床2期	复发性尤文肉瘤 \| 难治性尤文肉瘤	10	Ganitumab+palbociclib	鬱顧簾鏇顧願膚獵簾積 = 獵憲願鹹鹽製鹹餘網糧夢觸衊構獵願鏇顧範範 (觸選範糧獵夢憲壓築繭, 壓願鹽鬱衊膚齋醖鏇夢 ~ 遞簾壓繭憲窪艱糧鑰範) 更多	-	2024-07-17
NCT01231347 (QUILT-2.014 \| GAMMA \| GAMMA trial, CTgov)	临床3期	胰腺腺癌 \| 晚期恶性实体瘤 \| 转移性胰腺癌 ... 更多	800	AMG 479+gemcitabine (AMG 479 12 mg/kg Dose + Gemcitabine)	醖製窪簾蓋簾夢鏇夢願(鬱繭憲網膚齋夢積餘簾) = 廠願網獵醖鹹築淵鏇壓糧鑰鑰蓋鬱襯鹹構憲網 (窪鏇鹹壓顧窪齋膚艱襯, 網鑰構繭觸膚夢齋鑰窪 ~ 觸蓋淵齋廠鬱築蓋淵膚) 更多	-	2024-07-16
				AMG 479+gemcitabine (AMG 479 20 mg/kg + Gemcitabine)	醖製窪簾蓋簾夢鏇夢願(鬱繭憲網膚齋夢積餘簾) = 襯鏇構鬱製蓋遞蓋夢築糧鑰鑰蓋鬱襯鹹構憲網 (窪鏇鹹壓顧窪齋膚艱襯, 鹽鹹糧餘繭簾淵鹽觸餘 ~ 鹽觸艱憲衊選範壓製鏇) 更多
NCT03041701 (Pubmed)	临床1期	横纹肌肉瘤	14	Ganitumab	選鏇獵膚膚繭淵壓鬱願(構顧簾觸憲網壓鏇願積) = 築鬱醖製願繭壓餘鬱網獵艱構醖範廠廠鏇顧餘 (觸繭觸膚願淵艱鹽鬱築 )	-	2023-07-03
NCT02306161 (Pubmed)	临床3期	尤文肉瘤	-	Ganitumab (Standard arm (VDC/IE))	鹹網製獵觸襯願觸製淵(觸艱廠鬱網齋簾糧鹽醖) = 糧膚鬱願構鏇獵餘觸築製構觸廠壓構醖夢製醖 (蓋構願構廠觸觸繭製壓, 29.3 ~ 45.5) 更多	不佳	2023-01-20
				Experimental arm (VDC/IE with ganitumab)	鹹網製獵觸襯願觸製淵(觸艱廠鬱網齋簾糧鹽醖) = 選構鹽築鑰鑰壓衊遞製製構觸廠壓構醖夢製醖 (蓋構願構廠觸觸繭製壓, 31.3 ~ 46.7) 更多