This study is an open-label, international, multi-center, Phase 2 study in adult patients with recurrent, locally-advanced or metastatic solid tumors, which harbor the NRG1 gene fusion.

开始日期2024-02-28

申办/合作机构

Elevation Oncology, Inc.

NCT03241810

/ Terminated临床2期

Randomized Phase 2 Trial of Seribantumab Plus Fulvestrant in Postmenopausal Women With Hormone Receptor-positive, Heregulin Positive (HRG+), HER2 Negative Metastatic Breast Cancer (Merrimack Pharmaceuticals Inc.)

This study is a multi-center, randomized, double-blind, placebo-controlled, Phase 2 study in postmenopausal women with heregulin positive, hormone receptor positive, HER2 negative metastatic, unresectable breast cancer.

开始日期2017-08-15

申办/合作机构

Elevation Oncology, Inc.

NCT02538627

/ Terminated临床1期

A Phase 1 Multi Arm Study Evaluating the Safety, Pharmacology and Preliminary Activity of the Co-Administration of MM-151 With Seribantumab (MM-121), Istiratumab (MM-141), or Trametinib in Biomarker-selected Cancer Patients

This is a Phase 1 open-label, dose-escalation trial using "3+3" design, evaluating MM-151 co-administration with MM-121, MM-141, and trametinib at varying dose levels.

开始日期2015-08-01

申办/合作机构

Merrimack Pharmaceuticals, Inc.

100 项与 Seribantumab 相关的临床结果

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100 项与 Seribantumab 相关的转化医学

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100 项与 Seribantumab 相关的专利（医药）

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项与 Seribantumab 相关的文献（医药）

2025-01-01·Current medicinal chemistry

The Therapeutic Significance of HER3 in Non-small Cell Lung Cancer (NSCLC): A Review Study

Article

作者: Ding, Ke ; Zhang, Jinwei ; Trinder, Amelia

HER3 (Human Epidermal Growth Factor Receptor 3) is frequently overexpressed in various cancers, including non-small cell lung cancer (NSCLC), with a prevalence of 83% in primary tumors. Its involvement in tumorigenesis and resistance to targeted therapies makes HER3 a promising target for cancer treatment. Despite being initially considered “undruggable” due to its lack of catalytic activity, significant progress has been made in the development of anti-HER3 therapeutics. Monoclonal antibodies such as lumretuzumab, seribantumab, and patritumab have shown potential in targeting HER3 to overcome resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Additionally, antibody-drug conjugates (ADCs) like HER3-DXd (patritumab deruxtecan) are new drug candidates that have demonstrated selective delivery of cytotoxic chemicals to NSCLC cells by exploiting HER3's widespread expression, minimizing cytotoxicity. This review aims to evaluate the efficacy of current HER3 therapeutics in development and their therapeutic potential in NSCLC, incorporating evidence from clinical trials.

2024-11-05·Circulation

ErbB3 Governs Endothelial Dysfunction in Hypoxia-Induced Pulmonary Hypertension

Article

作者: Zhang, Junting ; Chen, Yuan ; Li, Yiying ; Yang, Xusheng ; Chen, Rongchang ; Deng, Lin ; Nie, Xiaowei ; Bian, Jin-Song ; Tan, Jianxin ; Chen, Jingyu

BACKGROUND::

Pulmonary hypertension, characterized by vascular remodeling, currently lacks curative therapeutic options. The dysfunction of pulmonary artery endothelial cells plays a pivotal role in the initiation and progression of pulmonary hypertension (PH). ErbB3 (human epidermal growth factor receptor 3), also recognized as HER3, is a member of the ErbB family of receptor tyrosine kinases.

METHODS::

Microarray, immunofluorescence, and Western blotting analyses were conducted to investigate the pathological role of ErbB3. Blood samples were collected for biomarker examination from healthy donors or patients with hypoxic PH. The pathological functions of ErbB3 were further validated in rodents subjected to chronic hypoxia- and Sugen-induced PH, with or without adeno-associated virus-mediated ErbB3 overexpression, systemic deletion, or endothelial cell–specific ErbB3 knockdown. Primary human pulmonary artery endothelial cells and pulmonary artery smooth muscle cells were used to elucidate the underlying mechanisms.

RESULTS::

ErbB3 exhibited significant upregulation in the serum, lungs, distal pulmonary arteries, and pulmonary artery endothelial cells isolated from patients with PH compared with those from healthy donors. ErbB3 overexpression stimulated hypoxia-induced endothelial cell proliferation, exacerbated pulmonary artery remodeling, elevated systolic pressure in the right ventricle, and promoted right ventricular hypertrophy in murine models of PH. Conversely, systemic deletion or endothelial cell–specific knockout of ErbB3 yielded opposite effects. Coimmunoprecipitation and proteomic analysis identified YB-1 (Y-box binding protein 1) as a downstream target of ErbB3. ErbB3 induced nuclear translocation of YB-1 and subsequently promoted hypoxia-inducible factor 1/2α transcription. A positive loop involving ErbB3-periostin-hypoxia–inducible factor 1/2α was identified to mediate the progressive development of this disease. MM-121, a human anti-ErbB3 monoclonal antibody, exhibited both preventive and therapeutic effects against hypoxia-induced PH.

CONCLUSIONS::

Our study reveals, for the first time, that ErbB3 serves as a novel biomarker and a promising target for the treatment of PH.

2022-11-01·JCO precision oncology

Clinical Response to Seribantumab, an Anti–Human Epidermal Growth Factor Receptor-3 Immunoglobulin 2 Monoclonal Antibody, in a Patient With Metastatic Pancreatic Ductal Adenocarcinoma Harboring an NRG1 Fusion

Article

作者: Thavaneswaran, Subotheni ; Deegan, Maegan ; Chan, Wei Yen ; Jansen, Valerie M. ; Grady, John P. ; Thomas, David M. ; Asghari, Ray

项与 Seribantumab 相关的新闻（医药）

2025-01-13

·PRNewswire

Elevation Oncology Provides Updates on Differentiated ADC Programs and Upcoming Milestones

-- Initiated dosing in Phase 1 clinical trial cohort evaluating Claudin 18.2 ADC EO-3021 in combination with ramucirumab or dostarlimab in patients with advanced gastric/gastroesophageal junction (GEJ) cancer -- -- Expect to report initial data from combination cohort in 4Q 2025 or 1Q 2026 -- -- On-track to report additional monotherapy data from dose escalation and expansion cohorts of ongoing Phase 1 clinical trial in 1H 2025 -- -- Plan to present preclinical data for HER3 ADC EO-1022 in 1H 2025 and file an Investigational New Drug (IND) application in 2026 -- BOSTON, Jan. 13, 2025 /PRNewswire/ -- Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, today announced program updates and upcoming milestones. "We are rapidly advancing EO-3021 to address significant unmet needs in treating earlier lines of advanced gastric/GEJ cancer, where we believe we have a unique ability to improve on the standard of care," said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. "As we enter 2025, we are honing our focus, leveraging the competitive anti-tumor activity and differentiated safety profile of EO-3021 to explore combination approaches in the first- and second-line settings. With our Phase 1 clinical trial ongoing and now enrolling both monotherapy and combination cohorts, we are in a leading position to explore the compelling potential of EO-3021, our differentiated Claudin 18.2 ADC, to improve outcomes for people living with advanced gastric/GEJ cancer." Mr. Ferra continued, "We look forward to sharing additional data from our Phase 1 dose escalation and expansion study of EO-3021 in the first half of 2025. With this readout, we aim to build on the promising initial data reported in August 2024, reinforcing EO-3021's robust anti-tumor activity and potential better combinability, while garnering additional insights to inform our go-forward clinical development efforts. We are enthusiastic about the potential of EO-3021 in addressing meaningful market opportunities and look forward to a transformative 2025." Program Updates and Upcoming Milestones EO-3021: Elevation Oncology is developing EO-3021, a differentiated, potentially best-in-class antibody drug conjugate (ADC) for the treatment of patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2, including gastric/GEJ cancer. In August 2024, Elevation Oncology reported promising initial monotherapy data from the dose escalation portion of its ongoing Phase 1 clinical trial of EO-3021, demonstrating competitive efficacy, with a 42.8% confirmed overall response rate (ORR) in a biomarker-enriched population, and a differentiated safety profile, including minimal hematological toxicity and hepatotoxicity, and no peripheral neuropathy/hypoesthesia. Based on these data, Elevation Oncology is focusing the clinical development of EO-3021 on the first- and second-line treatment of advanced gastric/GEJ cancer, where EO-3021's key attributes can potentially provide differentiated benefits and address unmet needs in both patient outcomes and safety. Monotherapy : The dose expansion portion of Elevation Oncology's Phase 1 clinical trial of monotherapy EO-3021 is ongoing. As of January 2025, Elevation Oncology has implemented prospective Claudin 18.2 expression testing as part of the patient screening process, focusing enrollment on patients with ≥25% of tumor cells at IHC 1+/2+/3+. Elevation Oncology expects to report additional safety and efficacy data from the dose escalation and expansion portions of the study in the first half of 2025. Combination: Patient dosing is ongoing in the combination portion of Elevation Oncology's Phase 1 clinical trial of EO-3021. The combination cohorts are evaluating EO-3021 in combination with dostarlimab, a PD-1 inhibitor, in the first line setting and with ramucirumab, a VEGFR2 inhibitor, in the second line setting. By combining EO-3021 and dostarlimab, an immune checkpoint inhibitor, Elevation Oncology aims to deliver synergistic benefit, potentially offering patients improved outcomes beyond those seen with the existing combination of immunotherapy and chemotherapy. The combination of an immunotherapy and chemotherapy agent is the standard of care for the treatment of gastric/GEJ cancer in the front-line setting. With the EO-3021 and ramucirumab combination, Elevation Oncology aims to deliver improved tolerability and synergistic anti-tumor activity compared to the approved combination of ramucirumab and paclitaxel. The combination of ramucirumab and paclitaxel is the standard of care for the treatment of second-line gastric/GEJ cancer. Elevation Oncology expects to report initial data from the combination cohorts in the fourth quarter of 2025 or the first quarter of 2026. EO-1022: Elevation Oncology is developing EO-1022, a differentiated HER3 ADC for the treatment of patients with HER3-expressing solid tumors, including breast cancer, EGFR-mutant non-small cell lung cancer, and pancreatic cancer. EO-1022 combines seribantumab, a fully human anti-HER3 monoclonal antibody, and a monomethyl auristatin E (MMAE) payload with site-specific conjugation to glycan. It is designed to leverage seribantumab's desirable internalization capability and the latest site-specific ADC technology to deliver a safe, effective option for patients living with solid tumors that express HER3. Elevation Oncology expects to present preclinical data for EO-1022 in the first half of 2025 and to file an IND application in 2026. Financial Guidance Elevation Oncology expects that its cash, cash equivalents and marketable securities as of September 30, 2024, will be sufficient to fund its current operations into 2026. About Elevation Oncology, Inc. Elevation Oncology is an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs. We are leveraging our ADC expertise to advance a novel pipeline, initially targeting two clinically validated targets in oncology, Claudin 18.2 and HER3. Our lead candidate, EO-3021, is a potential best-in-class, Claudin 18.2 ADC and is currently being evaluated in a Phase 1 trial (NCT05980416) as a monotherapy, and in combinations with dostarlimab or ramucirumab, in patients with advanced, unresectable or metastatic gastric/gastroesophageal adenocarcinoma that express Claudin 18.2. We are also advancing EO-1022, a HER3 ADC for the treatment of patients living with solid tumors that express HER3, through preclinical development. For more information, visit . Forward-Looking Statements This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, anticipated clinical and preclinical development activities, expected timing of announcements of clinical and preclinical results, potential benefits of product candidates, potential market opportunities for product candidates, the ability of product candidates to treat their targeted indications and Elevation Oncology's expectations about its cash runway. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These forward-looking statements may be accompanied by such words as "aim," "anticipate," "believe," "could," "estimate," "expect," "forecast," "goal," "intend," "may," "might," "plan," "possible," "potential," "will," "would," and other words and terms of similar meaning. Although Elevation Oncology believes that the expectations reflected in such forward-looking statements are reasonable, Elevation Oncology cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval are inherently uncertain. Forward-looking statements are subject to risks and uncertainties that may cause Elevation Oncology's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to Elevation Oncology's ability to advance its product candidates, the timing and results of preclinical studies and clinical trials, approvals and commercialization of product candidates, the receipt and timing of potential regulatory designations, Elevation Oncology's ability to fund development activities and achieve development goals, Elevation Oncology's ability to protect intellectual property, Elevation Oncology's ability to establish and maintain collaborations with third parties, and other risks and uncertainties described under the heading "Risk Factors" in documents Elevation Oncology files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and Elevation Oncology undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. Elevation Oncology Investor and Media Contact Gracie Tong Senior Director, Investor Relations and Corporate Communications [email protected] SOURCE Elevation Oncology WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床1期免疫疗法抗体药物偶联物临床结果

2024-12-25

·CPHI制药在线

HER3靶点进展浅谈，Zenocutuzumab率先获批

关注并星标CPHI制药在线 2024年10月，默沙东注射用MK-1022在国内获得临床试验默示许可，用于治疗胃肠道肿瘤。MK-1022（HER3-DXd，Patritumab deruxtecan）是采用第一三共技术设计的潜在首创HER3靶向ADC，由全人源化抗HER3 IgG1单克隆抗体通过可裂解四肽连接子与拓扑异构酶I抑制剂有效载荷（一种依喜替康衍生物，DXd）连接组成。（点击小图看大图） 2021年12月，MK-1022被FDA授予突破性疗法认定，用于治疗EGFR突变的局部晚期或转移性非小细胞肺癌（NSCLC）患者，这些患者在接受第三代酪氨酸激酶抑制剂（TKI）和铂类药物治疗期间或治疗后出现疾病进展。 2023年10月，第一三共和默沙东就包括MK-1022在内的三款ADC签订全球开发和商业化协议，潜在交易总金额约220亿美元。据协议，默沙东获得这些产品在日本之外的全球开发及商业化权益。 2023年12月，MK-1022治疗既往接受过两种或两种以上全身治疗的局部晚期或转移性EGFR突变成人NSCLC的BLA获FDA受理，并被授予优先审查。该BLA是基于II期研究HERTHENA-Lung01的结果。 HERTHENA-Lung01研究在225例EGFR突变的局部晚期或转移性NSCLC患者中开展，这些患者既往接受过EGFR-TKI和含铂化疗后发生疾病进展。结果显示：接受MK-1022治疗患者的客观缓解率（ORR）为29.8%，中位缓解持续时间为6.4个月。安全性方面，HERTHENA-Lung01研究安全性扩展结果显示，MK-1022安全性可控，与既往报告一致。血液学和消化道TEAE通常发生在中位治疗（TX）周期的早期，未观察到其他安全信号。遗憾的是，2024年6月，第一三共和默沙东收到了FDA就该BLA发出的完整回复函（CRL），原因是第三方生产设施的问题。 2024年9月，默沙东/第一三共宣布MK-1022的III期研究HERTHENA-Lung02 达到主要终点PFS。该研究是一项全球性、多中心、开放标签试验，旨在评估每三周一次5.6 mg/kg MK-1022与四个周期的培美曲塞和铂类化疗相比，在转移性或局部晚期NSCLC患者中的疗效和安全性，这些患者携带EGFR激活突变（外显子19缺失或L858R）并接受过第三代EGFR TKI（包含奥希替尼、拉泽替尼、奥莫替尼、阿氟替尼）治疗后发生疾病进展。数据显示：与铂联合培美曲塞诱导化疗后再接受培美曲塞维持化疗相比，MK-1022治疗后患者实现显著的PFS统计学改善，达到主要终点。但在进行分析时，次要终点总生存期（OS）数据还不成熟。安全性方面，研究中观察到的安全性与之前临床试验中的安全性一致，没有发现新的安全信号。默沙东计划与全球监管单位就该研究结果进行进一步的讨论。 MK-1022是默沙东研发管线中进展最快的一款ADC，期待其可以早日通过监管批准，造福EGFR-TKI耐药的NSCLC患者。 ! HER3靶向药进展 HER3是EGFR/HER家族成员之一，没有或几乎没有细胞内酪氨酸激酶活性。虽然有报道称HER3具有一些激酶活性，但它比完全激活的EGFR激酶活性弱1000倍。与其他家族成员相比，HER3单独过表达时不具有致癌作用，但当其与神经调节蛋白（NRG）配体结合后，便会与其他RTK（受体酪氨酸激酶）形成异源二聚体。特别是HER3与HER2结合时，更是会形成HER2：HER3异源二聚体，导致PI3K/AKT和MEK/MAPK信号通路会被激活，促进细胞的分裂、增殖与分化，促进癌细胞的存活和发展。 HER3在正常成人的胃肠道、生殖系统、皮肤、神经系统、泌尿道等系统中均有表达，而其过度表达与前列腺癌、膀胱癌和乳腺癌等多种癌症相关。而且，已有研究证明HER3与EGFR、HER2疗法的耐药机制有关。鉴于HER2、EGFR耐药的广泛发生，HER3被认为可能是破解EGFR以及HER2靶点耐药性，进一步提升临床治疗潜力的关键所在。目前，全球监管机构仅批准一款HER3靶向药，即Zenocutuzumab。 Zenocutuzumab是Merus开发的一款靶向HER2/HER3的双抗，2023年6月被FDA授予突破性治疗认定，用于治疗既往全身治疗进展后或没有令人满意的替代治疗方案的NRG1+胰腺癌。2023年7月，该药被FDA授予第二项突破性治疗认定，用于NRG1融合阳性NSCLC。 ESMO 2023大会上公布的数据显示：在晚期NRG1+ NSCLC患者中，研究者根据RECIST 1.1版评估的ORR为37.2%，mDOR为14.9个月；在晚期NRG1+胰腺导管腺癌中，研究者根据RECIST 1.1版评估的ORR为42.4%，mDOR为9.1个月。安全性方面，研究中观察到61%的患者出现任何级别的TRAEs，包括5%的3/4级TRAEs。最常见的任何级别的TRAEs包括腹泻（21%）、乏力/疲劳（12%）、输液相关反应（15%）和恶心（10%）。此外，不到1%的患者因毒性而停止治疗。 2024年5月，FDA受理Zenocutuzumab治疗NRG1+ NSCLC和胰腺癌的BLA，同时授予该BLA优先审评资格。2024年12月，FDA批准Zenocutuzumab用于治疗NRG1+胰腺癌和非小细胞肺癌，商品名为Bizengri。此外，据不完全统计全球还有几款HER3靶向药，详见下表。HER3靶向药药物类型多样，涉及单抗、ADC和双抗ADC。（点击小图看大图） HER3靶向单抗中的Seribantumab可抑制NRG1融合蛋白启动的信号传导，从而引导癌细胞生长和增殖。临床前数据表明，Seribantumab可阻止携带NRG1基因融合的细胞中HER3信号的激活，并破坏ERBB家族信号传导途径的稳定性，其中包括HER2、EGFR和HER4的激活。2024年4月，Seribantumab被FDA授予快速通道指定，用于治疗携带NRG1基因融合的晚期实体瘤。 HER3靶向ADC中的YL202/BNT326是基于宜联生物的TMALIN®技术所开发的一款靶向人HER3的下一代ADC。2023年10月，宜联生物与BioNTech就YL202达成战略合作和全球许可协议。 ASCO 2024年会上公布的YL202首次临床研究数据显示：截至2024年4月16日，该项中、美同步开展的I期临床爬坡共计入组55人（NSCL 40人，BC 15人），累计爬坡7个剂量组（0.5 – 5.5 mg/kg Q3W）。全部剂量下共51例可评估病例，ORR为42.3%，DCR为94.2%，mPFS为6.0月，mDOR为5.8月。其中3.0mg/kg剂量组ORR为60.0%，DCR为100%。在EGFRm NSCLC末线人群中，全部爬坡剂量下ORR为39.4%（15/38）；在HR+/HER2- BC末线人群中，全部爬坡剂量下ORR为53.8%（7/13）。安全性方面，常见治疗相关安全事件包括白细胞计数减少、中性粒细胞减少等血液学副作用。在爬坡过程中，5.5mg/kg剂量组下出现一例DLT事件（三级粒缺伴发热）。在回填过程中，4.0mg/kg和5.5mg/kg剂量组下分别出现2例（中性粒和血细胞减少）和1例受试者死亡（新冠感染后间质性肺炎）。考虑到YL202在较高剂量下，可能会使人类受试者面临不合理和重大的疾病或伤害风险，6月17日，FDA对由MediLink赞助的YL202/BNT326多中心、开放标签、首次人体1期临床（NCT05653752）试验进行部分临床搁置。不过8月，FDA解除了该部分临床搁置。 SHR-A2009是恒瑞医药自主研发的一款以HER3为靶点的ADC，由全人抗HER3 IgG1 mAb、可切割肽接头和 DNA 拓扑异构酶I抑制剂组成。2024年1月，SHR-A2009被FDA授予快速通道资格(FTD)，用于治疗经第三代EGFR酪氨酸激酶抑制剂和含铂化疗后疾病进展的EGFR突变的转移性NSCLC。 ESMO 2024上公布的SHR-A2009治疗晚期实体瘤I期临床的EGFR突变NSCLC队列数据显示：截止2024年3月30日，共103例EGFR突变NSCLC患者入组并接受治疗，中位随访时间8.6 个月。在以9.0mg/kg的扩展剂量治疗的患者中(n = 52)，可评估患者的ORR为46.9%，DCR为 93.9%，mPFS为为 9.6 个月。安全性方面，103例患者中有56.3%报告了≥3 级治疗相关不良事件（TRAE），所有发生率≥5% 的均为血液毒性。TRAE导致8.7%的患者停药，8.7%的患者发生间质性肺病。 HER3靶向双抗ADC中的BL-B01D1是百利天恒研发的一种基于双特异性拓扑异构酶抑制剂的ADC，由通过基于四肽的可切割接头与新型拓扑异构酶I抑制剂有效载荷（Ed-04）连接的 EGFR /HER3靶向双抗组成，在多种实体瘤中展现出令人鼓舞的抗肿瘤活性。 2023年12月，百利天恒与百时美施贵宝就BL-B01D1达成一项84亿美元的独家许可与合作协议，刷新了中国创新药出海授权纪录。 BL-B01D1曾被CDE授予4项突破性疗法认定，分别用于治疗既往经PD-1/PD-L1单抗治疗且经至少两线化疗（至少一线含铂）治疗失败的复发性或转移性鼻咽癌、既往经抗PD-1/PD-L1单抗治疗且经含铂化疗治疗失败的局部晚期或转移性EGFR野生型NSCLC、经EGFR-TKI治疗失败的EGFR敏感突变的局部晚期或转移性非鳞状NSCLC和既往经PD-1/PD-L1单抗联合含铂化疗治疗失败的复发性或转移性食管鳞癌。 JSKN016是康宁杰瑞利用特有的糖定点偶联平台自主研发的一款靶向HER3和人滋养细胞表面抗原2（TROP2）的ADC，其可诱导TROP2或者HER3阳性的肿瘤细胞凋亡，同时释放的细胞毒性药物穿透细胞膜进入到抗原阴性的肿瘤细胞中发挥旁观者效应，从而有效抑制肿瘤细胞生长。2024年5月，JSKN016在中国晚期恶性实体瘤患者中开展的Ⅰ期临床研究完成首例患者给药。 ! 总结 HER3是肿瘤药研发的潜力靶点，有望破解EGFR和HER2抑制剂耐药问题。目前，全球监管机构仅批准1款HER3靶向药，多款处于临床试验阶段。在研HER3靶向药药物类型多样，大多集中在ADC，尤其是双抗ADC。 END 【智药研习社近期直播】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

突破性疗法优先审批临床结果抗体药物偶联物临床3期

2024-12-14

·PipelineReview

Elevation Oncology Expands Pipeline with Nomination of EO-1022, a HER3 ADC for the Treatment of HER3-expressing Solid Tumors

— EO-1022 is comprised of seribantumab, an anti-HER3 monoclonal antibody, and an MMAE payload – — Following recently signed global license agreement with Synaffix, EO-1022 leverages the company’s GlycoConnect® and HydraSpace® ADC technologies for glycan site-specific conjugation and SYNstatin E™ linker-payload — – Elevation Oncology expects to present EO-1022 preclinical data in 1H 2025 and to file an IND application in 2026 – BOSTON, MA, USA I December 12, 2024 I Elevation Oncology, Inc. (Nasdaq: ELEV ), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, today announced the nomination of EO-1022 as its HER3 ADC development candidate. EO-1022 is currently progressing through preclinical development, and Elevation Oncology expects to file an investigational new drug (IND) application in 2026. HER3 is a protein expressed across several types of solid tumors, including breast cancer, EGFR-mutant non-small cell lung cancer and pancreatic cancer, and often associated with poor clinical outcomes. EO-1022 is a differentiated ADC containing seribantumab, an anti-HER3 monoclonal antibody (mAb), and a monomethyl auristatin E (MMAE) payload, with site-specific conjugation to the glycan. EO-1022 is being developed for the treatment of patients living with solid tumors that express HER3. “The nomination of our HER3-ADC development candidate marks a key milestone for Elevation Oncology in bolstering our ADC pipeline. EO-1022 combines the seribantumab antibody and state-of the-art ADC site-specific technology. We believe seribantumab is ideally-suited to be used in an ADC due to its selectivity in delivering cytotoxic payload to HER3-expressing cancer cells and its well-tolerated safety profile demonstrated in over 900 patients in multiple studies,” said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. “This program is another step forward in leveraging our ADC and oncology drug development expertise to develop innovative, selective cancer therapies that address significant unmet needs. We look forward to sharing preclinical data for EO-1022 in the first half of 2025, as we continue to advance this asset toward the clinic.” Also today, Elevation Oncology announced that it has entered into a licensing agreement with Synaffix B.V. (Synaffix). This licensing agreement gives Elevation Oncology global access to Synaffix’s clinical stage, site-specific ADC technology platform, including GlycoConnect® antibody conjugation technology, HydraSpace® polar spacer technology, as well as the toxSYN® linker-payload, SYNstatin E™. The license granted to GlycoConnect® and HydraSpace® technologies is exclusive to HER3 as a single target in combination with SYNstatin E® linker-payload. “HER3 is broadly expressed in various cancer types, making it a compelling target for innovative therapeutic strategies. We believe an ADC approach is uniquely positioned to fully unlock the clinical potential of HER3,” said David Dornan, Ph.D., Chief Scientific Officer of Elevation Oncology. “We are excited to nominate EO-1022, which leverages Synaffix’s state-of-the art site-specific conjugation and differentiated linker-payload for a potentially best-in-class profile. We look forward to advancing our pipeline, as we work towards transforming the care and treatment of patients living with solid tumors that overexpress HER3.” “As a dedicated partner in the ADC space, Synaffix is excited to collaborate with Elevation Oncology to push the boundary of ADC innovation,” said Peter van de Sande, Head of Synaffix. “With our state-of-the-art ADC technology platform and established supply chain, Elevation is well-positioned to accelerate the development of its differentiated HER3 ADC.” About Elevation Oncology, Inc. Elevation Oncology is an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs. We are leveraging our ADC expertise to advance a novel pipeline, initially targeting two clinically validated targets in oncology, Claudin 18.2 and HER3. Our lead candidate, EO-3021, is a potential best-in-class, Claudin 18.2 ADC and is currently being evaluated in the dose expansion portion of a Phase 1 trial ( NCT05980416 ) in patients with advanced, unresectable or metastatic gastric/gastroesophageal adenocarcinoma that express Claudin 18.2. We are also advancing EO-1022, a HER3-targeting ADC for the treatment of patients living with solid tumors that express HER3, through preclinical development. For more information, visit www.ElevationOncology.com . About Synaffix Synaffix B.V. is a biotechnology company that enables ADC product candidates using its clinical-stage, site-specific ADC technology platform based on GlycoConnect®, HydraSpace® and toxSYN® technologies, that together enable any company with an antibody to develop proprietary best-in-class ADC products under a single license from Synaffix. The Synaffix platform enables a rapid timeline to clinic due to the established supply chain of technology components. Synaffix holds granted patents to its technology. The business model of Synaffix is target-specific technology out-licensing, as exemplified through its existing deals with ADC Therapeutics, Mersana Therapeutics, Shanghai Miracogen (acquired by Lepu Biopharma), Innovent Biologics, Kyowa Kirin, Genmab, Macrogenics, Amgen, Hummingbird Biosciences, Chong Kun Dang Pharma, ABL Bio, SOTIO Biotech, Kivu Bioscience, BigHat Biosciences, Illumina and Elevation Oncology. Synaffix was fully acquired by Lonza (SIX:LONN) in June 2023. SOURCE: Elevation Oncology

临床1期引进/卖出抗体药物偶联物并购

100 项与 Seribantumab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11777	Seribantumab	-	DB11857

研发状态

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
胆管癌	临床2期	美国	Elevation Oncology, Inc.	2024-02-28
胆管癌	临床2期	澳大利亚	Elevation Oncology, Inc.	2024-02-28
胆管癌	临床2期	加拿大	Elevation Oncology, Inc.	2024-02-28
胆管癌	临床2期	韩国	Elevation Oncology, Inc.	2024-02-28
膀胱癌	临床2期	美国	Elevation Oncology, Inc.	2024-02-28
膀胱癌	临床2期	澳大利亚	Elevation Oncology, Inc.	2024-02-28
膀胱癌	临床2期	加拿大	Elevation Oncology, Inc.	2024-02-28
膀胱癌	临床2期	韩国	Elevation Oncology, Inc.	2024-02-28
乳腺癌	临床2期	澳大利亚	Elevation Oncology, Inc.	2024-02-28
乳腺癌	临床2期	韩国	Elevation Oncology, Inc.	2024-02-28

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临床结果

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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


WCLC2024	N/A	NRG1融合阳性非小细胞肺癌	-	Seribantumab	製鑰網構選餘醖衊觸糧(築壓窪範鬱壓夢糧鹹簾) = 醖構網遞築積蓋齋願選顧獵繭鏇餘夢餘選鑰簾 (艱鑰範鹹範繭糧齋構襯 )	-	2024-09-09
NCT04383210 (CRESTONE, AACR2023) 人工标引	临床2期	实体瘤二线 NRG1 Expression	51	seribantumab 3g	鑰鬱襯鹽壓鏇鏇淵築齋(艱鑰網繭簾鬱範醖淵製) = 淵簾襯醖淵廠蓋範繭選簾鬱鑰範築廠艱壓積襯 (鏇選餘鏇憲鏇鏇壓夢鬱 ) 更多	积极	2023-04-14
NCT04383210 (CRESTONE, ASCO2022)	临床2期	肉瘤 \| 转移性实体瘤 \| NRG1融合阳性实体瘤 ... 更多	12	Seribantumab 3g QW	艱窪鏇繭顧鏇齋觸窪蓋(憲築製餘願淵夢簾築觸) = 壓繭齋構製蓋鏇觸鑰構範構蓋繭觸糧製膚獵憲 (壓獵廠鬱獵願鹽蓋鏇膚 )	-	2022-06-02
NCT00734305 (Pubmed) 人工标引	临床1期	实体瘤	44	Seribantumab (dose escalation)	積願選蓋壓觸製願遞淵(糧糧築鹽鑰蓋網鏇餘廠) = maximum tolerated dose was not reached. 廠顧構選淵憲鹹簾觸壓 (蓋繭糧艱膚餘繭醖遞衊 ) 更多	积极	2021-12-01
				Seribantumab (dose expansion)
NCT02387216 (SHERLOC, CTgov)	临床2期	腺癌 \| 转移性非小细胞肺癌	153	Docetaxel+MM-121 (Arm A (Experimental): MM-121 in Combination With Docetaxel)	鑰夢願鹽觸鏇艱艱獵築(餘艱築遞範廠壓鹹範蓋) = 窪鏇艱窪選餘簾廠簾膚醖選壓範範觸觸積範鏇 (範衊餘衊鹽範鑰衊鹽鹹, 願餘夢顧蓋觸淵餘獵遞 ~ 觸憲鑰淵鬱餘衊願選艱) 更多	-	2021-10-12
				Docetaxel (Arm B (Comparator): Docetaxel Alone)	鑰夢願鹽觸鏇艱艱獵築(餘艱築遞範廠壓鹹範蓋) = 獵鹹積遞襯簾鏇範鑰網醖選壓範範觸觸積範鏇 (範衊餘衊鹽範鑰衊鹽鹹, 蓋夢簾鹹獵壓構築膚構 ~ 網顧憲獵憲艱顧齋齋願) 更多
NCT03241810 (SHERBOC, CTgov)	临床2期	HER2阳性转移性乳腺癌 \| 转移性乳腺癌 \| HR阳性/HER2阴性乳腺癌	22	Fulvestrant+Seribantumab (Arm A (Experimental): Seribantumab and Fulvestrant)	獵築齋壓網願膚遞蓋遞(範淵選顧餘顧齋鬱憲艱) = 鬱築製繭鹹壓鹽膚製遞鏇願餘願糧鹽鑰遞選鑰 (鹽構衊築鹹淵鑰壓鏇鹹, 襯壓鑰鬱襯積醖製壓願 ~ 範積網積積觸夢襯醖鹹) 更多	-	2020-09-02
				Placebo+Fulvestrant (Arm B (Control): Placebo and Fulvestrant)	獵築齋壓網願膚遞蓋遞(範淵選顧餘顧齋鬱憲艱) = 齋醖醖膚鬱醖選簾構餘鏇願餘願糧鹽鑰遞選鑰 (鹽構衊築鹹淵鑰壓鏇鹹, 選窪膚簾襯繭獵醖觸鹽 ~ 簾蓋夢夢築鏇膚顧網構) 更多
NCT02387216 (Pubmed \| Oncologist)	临床2期	EGFR突变的非小细胞肺癌	153	Seribantumab + Erlotinib	鹽範襯艱網膚壓鏇構選(積鹹選夢憲壓選窪淵網) = 鹹夢鑰衊遞顧製襯遞壓網築餘窪糧選觸壓鹽選 (窪鑰壓網艱齋齋構製繭 ) 更多	-	2019-08-01
				Erlotinib alone	鹽範襯艱網膚壓鏇構選(積鹹選夢憲壓選窪淵網) = 糧壓齋鏇鹽膚製製膚淵網築餘窪糧選觸壓鹽選 (窪鑰壓網艱齋齋構製繭 ) 更多
NCT02387216 (SHERLOC, ASCO 12019 \| ASCO 22019) 人工标引	临床2期	非小细胞肺癌 HRG positive	108	docetaxel 75 mg+MM-121 3000 mg	壓遞壓鹽廠築鹹艱壓壓(範鹹艱膚鑰網糧繭願蓋) = 製衊選網膚鹽範簾選鬱廠淵衊窪簾構選選餘選 (衊獵膚衊範糧鹹膚餘醖 ) 更多	不佳	2019-06-02
				docetaxel 75 mg	壓遞壓鹽廠築鹹艱壓壓(範鹹艱膚鑰網糧繭願蓋) = 鑰膚糧壓築遞範蓋衊範廠淵衊窪簾構選選餘選 (衊獵膚衊範糧鹹膚餘醖 ) 更多
NCT01447706 (CTgov)	临床2期	腹膜癌 \| 卵巢上皮癌 \| 铂耐药性卵巢癌 ... 更多	223	Paclitaxel	繭鹹鑰夢觸鏇鹹選積衊(鑰餘齋鹽鑰襯網顧淵糧) = 築窪憲衊簾淵繭齋構艱鑰繭鑰餘願觸簾齋壓餘 (醖簾壓築遞衊觸窪夢襯, 範壓衊願膚鹹夢廠艱蓋 ~ 遞遞壓構廠夢顧鬱糧繭) 更多	-	2016-05-12
NCT01151046 (CTgov)	临床2期	HER2 阴性乳腺癌	118	Placebo+Exemestane	襯簾願鹹鏇餘衊憲艱淵(範鹹觸鬱餘範顧襯築淵) = 選襯膚壓鬱衊壓築鬱顧廠鏇鏇襯鹽築糧艱選築 (廠壓鏇衊鹹顧艱繭憲夢, 積繭製範獵糧製願鬱糧 ~ 夢觸鬱糧鹽壓膚鏇鏇夢) 更多	-	2016-05-12