Exploratory Clinical Study of SHR-A1811 Combined with Apatinib in the Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma and Colorectal Cancer

To evaluate the effectiveness and safety of SHR-A1811 combined with apatinib in the treatment of advanced gastric or gastroesophageal junction adenocarcinoma and colorectal cancer.

开始日期2024-12-01

申办/合作机构

中國醫藥大學

[+1]

NCT06649331 / Recruiting临床2期IIT

Platform Study of ADC Rechallenge in ADC-treated Metastatic Breast Cancer：A Prospective, Open-label, Multicenter, Phase II Trial

This is a prospective, open-label, multicenter, phase II platform trial. The purpose of this study is to test the safety and effectiveness of the antibody-conjugated drugs (ADCs) in patients with advanced breast cancer who had previously used antibody-conjugated drugs.

开始日期2024-10-21

申办/合作机构

复旦大学

NCT06592625 / Not yet recruiting临床2期

A Multicenter, Single-arm, Phase 2 Study of Neoadjuvant SHR-A1811 Plus Adebrelimab Injection for Early-stage or Locally Advanced HR Negative or Low Expression/HER2 Low Expression Breast Cancer

The study is being conducted to evaluate the preliminary efficacy, safety, and pharmacokinetic characteristics of the combination of SHR-A1811 with Adebrelimab Injection in treatment-naive patients with early-stage or locally advanced HR-negative or low expression, HER2 low expression breast cancer.

开始日期2024-09-20

申办/合作机构

苏州盛迪亚生物医药有限公司

100 项与瑞康曲妥珠单抗相关的临床结果

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100 项与瑞康曲妥珠单抗相关的转化医学

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100 项与瑞康曲妥珠单抗相关的专利（医药）

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项与瑞康曲妥珠单抗相关的文献（医药）

2024-10-10·JOURNAL OF CLINICAL ONCOLOGY

Safety, Efficacy, and Pharmacokinetics of SHR-A1811, a Human Epidermal Growth Factor Receptor 2–Directed Antibody-Drug Conjugate, in Human Epidermal Growth Factor Receptor 2–Expressing or Mutated Advanced Solid Tumors: A Global Phase I Trial

Article

作者: Zhang, Jian ; Yen, Chia-Jui ; Wu, Xinhong ; Yin, Yongmei ; Lin, Yung-Chang ; Shen, Yu ; Zhu, Xiaoyu ; Barve, Minal ; Ganju, Vinod ; Song, Erwei ; Liu, Caigang ; Kaubisch, Andreas ; Zhao, Kaijing ; Wu, Lingying ; Park, John J. ; Roy, Amitesh C. ; Tong, Zhongsheng ; Gu, Shanzhi ; Ye, Changsheng ; Yao, Herui ; Rong, Shangyi ; Im, Seock-Ah ; Kim, Jee Hyun ; Voskoboynik, Mark ; Bao, Lequn ; Zhong, Yahua ; Zhao, Yiming ; Liu, Kan ; Li, Hui ; Bai, Li-Yuan ; Ryu, Min-Hee ; Yan, Min ; Wang, Shouman

PURPOSE:

SHR-A1811 is an antibody-drug conjugate composed of an anti–human epidermal growth factor receptor 2 (HER2) antibody trastuzumab, a cleavable linker, and a topoisomerase I inhibitor payload. We assessed the safety, tolerability, antitumor activity, and pharmacokinetics of SHR-A1811 in heavily pretreated HER2-expressing or mutated advanced solid tumors.

METHODS:

This global, multi-center, first-in-human, phase I trial was conducted at 33 centers. Patients who had HER2-expressing or mutated unresectable, advanced, or metastatic solid tumors and were refractory or intolerant to standard therapies were enrolled. SHR-A1811 was administered intravenously at doses ranging from 1.0 to 8.0 mg/kg once every 3 weeks. The primary end points were dose-limiting toxicity, safety, and the recommended phase II dose.

RESULTS:

From September 7, 2020, to February 27, 2023, 307 patients who had undergone a median of three (IQR, 2-5) previous treatment regimens in the metastatic setting received SHR-A1811 treatment. As of data cutoff (February 28, 2023), one patient from the 6.4 mg/kg group experienced dose-limiting toxicities (pancytopenia and colitis). The most common grade 3 or higher adverse events (AEs) included decreased neutrophil count (119 [38.8%]) and decreased WBC count (70 [22.8%]). Interstitial lung disease occurred in only eight (2.6%) patients. Serious AEs and deaths occurred in 70 (22.8%) and 13 (4.2%) patients, respectively. SHR-A1811 led to objective responses in 59.9% (184/307) of all patients, 76.3% (90/118) of HER2-positive breast cancer, 60.4% (55/91) of HER2 low-expressing breast cancer, and 45.9% (39/85 with evaluable tumor responses) of the 98 nonbreast tumors.

CONCLUSION:

SHR-A1811 exhibited acceptable tolerability, promising antitumor activity, and a favorable pharmacokinetic profile in heavily pretreated advanced solid tumors. The recommended phase II dose of 4.8 or 6.4 mg/kg was selected for various tumor types.

2021-12-01·Bulletin du cancer4区 · 医学

4区 · 医学

Review

作者: Deluche, Élise ; Vincent-Salomon, Anne

HER2, a human epidermal growth factor, being activated by amplification, is a negative prognostic factor in breast cancer. HER2 is the target of anti-HER2 antibodies (Trastuzumab, Pertuzumab…). For more than 10 years, breast cancers have been classified into HER2 positive and HER2 negative. However, the advent of new cytotoxic drugs combined with anti-HER2 antibodies, such as TDM1 or trastuzumab déruxtécan, have shown very promising therapeutic activity in patients with low HER2 expression breast cancer. These new therapeutic perspectives encourage a better identification of low HER2 tumours in order to identify patients who could benefit from them. Thus, the classification of breast tumours evolves to individualize HER2-negative tumours (score 0), HER2-positive tumours (score 3+ and 2+ amplified) and HER2-low tumours (scores 1+ and 2+ not-amplified). HER2-low tumours are common and represent more than half of all breast cancers. To identify these HER2-low tumours, pathology laboratories should not change their usual technique calibrated according to ASCO/CAP and GEFPICS recommendations. Until more clinical data about response to these new treatment strategies are available, GEFPICS does not require pathologists to identify this HER2-low category. Nevertheless, this designation will allow clinicians to identify patients whose tumours fall into this category in the very short term and offer them new treatment options.

2020-05-01·American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

Escalating and De-escalating Therapy for Early-Stage HER2-Positive Breast Cancer

Article

作者: File, Danielle ; Curigliano, Giuseppe ; Carey, Lisa A.

Untreated, HER2+ disease is the most aggressive breast cancer phenotype; however, the development of multiple highly effective HER2-targeting drugs has transformed treatment and survival. These drugs include the anti-HER2 monoclonal antibodies trastuzumab and pertuzumab; small molecule inhibitors lapatinib, neratinib, and tucatinib; and antibody-drug conjugates trastuzumab emtansine (T-DM1) and now trastuzumab deroxtecan. More complex regimens using these drugs continue to improve outcomes, but the incremental benefits of these advances are often modest. Improved outcomes came from the addition of HER2-targeted therapies to conventional chemotherapy, beginning with trastuzumab, then pertuzumab added to trastuzumab, or with neratinib given for the year after trastuzumab. Neoadjuvant, or preoperative, administration of chemotherapy plus HER2-targeting allows surgical deescalation and tailoring treatment by pathologic complete response (pCR) to therapy. Patients with pCR after conventional therapy have excellent outcomes; what we now know is that the poorer outcomes associated with residual disease can be ameliorated with adjuvant T-DM1. However, as we have developed more complex, effective, and expensive therapy to maximize outcomes, it is also true that we are overtreating many patients. In stage I HER2+ breast cancer, there are excellent outcomes with paclitaxel plus trastuzumab or T-DM1 alone. Higher clinical stage HER2+ disease is still treated aggressively, although intrinsic subtype or activated immune tumor microenvironment may identify those with augmented treatment response or better outcome. It is likely that future strategies to escalate and de-escalate treatment with less chemotherapy, fewer anti-HER2 drugs, or shorter duration will depend upon integrated clinical and genomic modeling.

329

项与瑞康曲妥珠单抗相关的新闻（医药）

2024-11-06

·ioncology

SABCS 2024盛幕将启，中国之声唱响全球！

点击蓝字，关注我们编者按：第47届圣安东尼奥乳腺癌研讨会（SABCS）将于当地时间2024年12月10日至13日在美国得克萨斯州圣安东尼奥举行。日前，官网已公布摘要题目，肿瘤瞭望特将General Session、Poster Spotlight Sessions和Year in Review等环节中国专家报告内容进行汇总，以飨读者。 General Session 1 时间：12月11日9:15 – 11:30 am 地点：Hall 1 GS1-03: Pyrotinib or placebo in combination with trastuzumab and docetaxel for untreated HER2-positive metastatic breast cancer (mBC): prespecified final analysis of progression-free survival (PFS) of the phase 3 PHILA trial. 吡咯替尼或安慰剂联合曲妥珠单抗和多西他赛用于未接受过治疗的HER2阳性转移性乳腺癌（mBC）：III期PHILA试验预设的无进展生存期（PFS）最终分析讲者：徐兵河（中国医学科学院肿瘤医院） GS1-04: HER2-Directed Antibody-Drug Conjugate SHR-A1811 in the Neoadjuvant Treatment of HER2-positive Early Breast Cancer: a Prospective, Randomized, Open-label, Phase 2 Trial. 靶向HER2的抗体-药物偶联物SHR-A1811用于HER2阳性早期乳腺癌的新辅助治疗：一项前瞻性、随机、开放标签的2期试验讲者：李俊杰（复旦大学附属肿瘤医院） General Session 3 时间：12月13日9:00 – 11:45 am 地点：Hall 1 GS3-06: Neoadjuvant camrelizumab plus chemotherapy (chemo) for early or locally advanced triple-negative breast cancer (TNBC): a randomized, double-blind, phase 3 trial. 卡瑞利珠单抗联合化疗（chemo）新辅助治疗早期或局部晚期三阴性乳腺癌（TNBC）：一项随机、双盲、3期试验讲者：邵志敏（复旦大学附属肿瘤医院） Concurrent Poster Spotlight Sessions 1, 3-5, 7 ▌Session 1: New Insights into Immune Biomarkers（免疫生物标志物的新见解）时间：12月11日7:00 – 8:30 am 地点：Room 221ABC 主持人：David Rimm, Yale University PS1-03: Prediction of Prognosis and Efficacy of Neoadjuvant Therapy in HER2-Positive Breast Cancer Patients Based on Tertiary Lymphoid Structures. 基于三级淋巴结构预测HER2阳性乳腺癌患者的预后和新辅助治疗的疗效讲者：张克兢（中南大学湘雅医院） ▌Session 3: Highlights on Novel Therapeutics（新型治疗亮点）时间：12月11日7:00 – 8:30 am 地点：Stars at Night 1-2 主持人：Sara Tolaney, Dana-Farber Cancer Institute PS3-01: Tislelizumab plus sitravatinib and nab-paclitaxel in patients with untreated locally recurrent or metastatic triple negative breast cancer (TNBC): updated efficacy and safety results. 替雷利珠单抗+sitravatinib+白蛋白结合型紫杉醇治疗未经治疗的局部复发或转移性三阴性乳腺癌（TNBC）：最新的疗效和安全性结果讲者：Xiyu Liu（复旦大学附属肿瘤医院） PS3-02: Induction of Cisplatin/abraxane/pembrolizumab followed by pembrolizumab ± Olaparib Maintenance in triple-negative Metastatic breast cancer patients (COMPLEMENT) – A Randomized, Open-label, Phase II Study. COMPLEMENT：一项随机、开放标签的II期研究，在转移性三阴性乳腺癌患者中，采用顺铂/白蛋白结核型紫杉醇/帕博利珠单抗诱导治疗，后续以帕博利珠单抗±奥拉帕利进行维持治疗讲者：胡夕春（复旦大学附属肿瘤医院） PS3-05: Evaluation of the safety and efficacy of ivonescimab in combination with chemotherapy as first-line (1L) treatment for triple-negative breast cancer (TNBC). 评估ivonescimab联合化疗作为三阴性乳腺癌（TNBC）一线（1L）治疗的安全性和有效性讲者：欧阳取长（湖南省肿瘤医院） PS3-08: Interim Overall Survival of Patients with Locally Advanced or Metastatic Triple-Negative Breast Cancer treated wtih First Line PM8002/BNT327 in Combination with Nab-Paclitaxel in Phase Ib/II Study. Ib/II期研究中，PM8002/BNT327联合白蛋白结合型紫杉醇一线治疗局部晚期或转移性三阴性乳腺癌患者的中期总生存讲者：吴炅（复旦大学附属肿瘤医院） ▌Session 4: Prediction of Chemotherapy Response（化疗疗效预测）时间：12月11日7:00 – 8:30 am 地点：Stars at Night 3-4 主持人：Sherene Loi, Peter Macallum Cancer Centre PS4-08: The tumor heterogeneous overexpressed CD155 promotes treatment resistance in HER2-positive breast cancer through immune microenvironment modulation. 肿瘤异质性CD155过表达通过调节免疫微环境促进HER2阳性乳腺癌的治疗抵抗讲者：Yi Zhang（复旦大学附属肿瘤医院） Concurrent Poster Spotlight Sessions 2, 6, 8, 9 and 15 ▌Session 2: Personalizing CDK 4/6 inhibitor therapy for patients with Metastatic Breast Cancer: Survival, QOL and biomarkers（转移性乳腺癌患者的个体化CDK 4/6抑制剂治疗：生存期、生活质量和生物标志物）时间：12月12日7:00 – 8:30 am 地点：Hemisfair Ballroom 1-2 主持人：Lisa Carey, Lineberger Comprehensive Cancer Center University of North Carolina PS2-01: Dalpiciclib versus placebo in combination with letrozole or anastrozole as first-line treatment for women with HR+/HER2- advanced breast cancer: prespecified final analysis of progression-free survival of the phase 3 DAWNA-2 trial. 3期DAWNA-2研究预设的无进展生存最终分析：达尔西利vs安慰剂联合来曲唑或阿那曲唑作为HR+/HER2-晚期乳腺癌女性患者一线治疗讲者：徐兵河（中国医学科学院肿瘤医院） PS2-02：Tibremciclib (BPI-16350) plus fulvestrant versus placebo plus fulvestrant for patients with HR+/HER2- advanced breast cancer after progressing on endocrine therapy: Updated analysis of the phase III study. 在内分泌治疗进展后的HR+/HER2-晚期乳腺癌患者，Tibremciclib（BPI-16350）联合氟维司群对比安慰剂联合氟维司群的疗效：III期研究的更新分析讲者：胡夕春（复旦大学附属肿瘤医院） PS2-06：First-line (1L) ribociclib (RIB) + endocrine therapy (ET) vs combination chemotherapy (combo CT) in clinically aggressive HR+/HER2- advanced breast cancer (ABC): a subgroup analysis of RIGHT Choice by intrinsic subtype & gene & signature expression. 一线（1L）瑞波西利（RIB）+内分泌治疗（ET）vs联合化疗（combo CT）治疗临床侵袭性HR+/HER2-晚期乳腺癌（ABC）：基于内在亚型、基因及特征表达的RIGHT Choice研究亚组分析讲者：卢彦伸（中国台湾大学医学院附属医院） PS2-10: Integrating ctDNA and Tumor Fraction Features for Deciphering Molecular Response and Resistance Mechanism to Endocrine Therapy and CDK4/6 Inhibition in Advanced HR-positive Metastatic Breast Cancer. 整合ctDNA和肿瘤组分特征以解析晚期激素受体阳性转移性乳腺癌对内分泌治疗和CDK4/6抑制剂的分子应答及耐药机制讲者：Hao Liao（北京大学肿瘤医院） ▌Session 8: Novel HER2 Therapeutics（新型HER2治疗）时间：12月12日7:00 – 8:30 am 地点：Stars at Night 1-2 主持人：Ian Krop, Yale School of Medicine PS8-01: ZN-1041, a potential best-in-class BBB Penetrable HER2 Inhibitor, has high antitumor activity in patients with Breast Cancer with CNS Metastases. ZN-1041是一种具有潜力的同类最佳血脑屏障（BBB）可穿透性HER2抑制剂，在中枢神经系统（CNS）转移乳腺癌患者中展现出高抗肿瘤活性讲者：马飞（中国医学科学院肿瘤医院） PS8-02: A Phase 1 study Evaluating the Safety, Efficacy and Pharmacokinetics of TL938 in HER2-Positive Patients with Advance Solid Tumors. 一项评价TL938治疗HER2阳性晚期实体瘤患者的安全性、疗效和药代动力学的1期研究讲者：石远凯（中国医学科学院肿瘤医院） PS8-05: ACE-Breast-08: a phase I study of ARX788, a novel anti-HER2 antibodydrug conjugate, in patients with TKI pretreated HER2 positive advanced breast cancer. ACE-Breast-08：一项I期研究，评估新型抗HER2抗体-药物偶联物ARX788在TKI预治疗的HER2阳性晚期乳腺癌患者中的疗效讲者：王晓稼（浙江省肿瘤医院） PS8-06: A randomized, open-label phase III study comparing disitamab vedotin (an anti-HER2 monoclonal antibody-MMAE conjugate) with lapatinib plus capecitabine in patients with HER2-positive, advanced breast cancer with liver metastasis. 一项随机、开放标签的III期研究，在伴肝转移的HER2阳性晚期乳腺癌患者中比较维迪西妥单抗（一种抗HER2单克隆抗体-MMAE偶联物）联合拉帕替尼联合卡培他滨的治疗疗效讲者：王佳玉（中国医学科学院肿瘤医院） PS8-07：Efficacy and Safety of GQ1005, a Promising HER2-ADC, in Patients with Metastatic HER2-Positive Breast Cancer. GQ1005（一种很有前景的HER2-ADC）治疗转移性HER2阳性乳腺癌患者的疗效和安全性讲者：王碧芸（复旦大学附属肿瘤医院） PS8-08: Efficacy and safety of SHR-A1811, an anti-HER2 antibody-drug conjugate (ADC), in 391 heavily pretreated multiple solid tumors with HER2-expression or mutations: a global, multi-center, first-in-human, phase 1 study. SHR-A1811是一种抗HER2抗体-药物偶联物（ADC），在391例既往接受过大量治疗且有HER2表达或突变的多种实体瘤中，SHR-A1811的疗效和安全性：一项全球性、多中心、首次人体1期研究讲者：姚和瑞（中山大学孙逸仙纪念医院） Concurrent Poster Spotlight Sessions 10-14 ▌Session 11: Imaging to Guide Breast Cancer Treatment – Molecular Imaging and AI（影像学指导乳腺癌治疗——分子影像学和人工智能）时间：12月13日7:00 – 8:30 am 地点：Hemisfair Ballroom 1-2 主持人：David Mankoff, Perelman School of Medicine University of Pennsylvania PS11-08: MRI improves multi-modal AI system for breast cancer diagnosis and prognosis. MRI提高了多模态AI系统对乳腺癌的诊断和预后判断讲者：Yanqi Xu（中国药科大学） ▌Session 12: Immunobiology Impact on Therapeutic Efficacy（免疫生物学对治疗效果的影响）时间：12月13日7:00 – 8:30 am 地点：Room 221ABC 主持人：Lajos Pusztai, Yale School of Medicine, New Haven, Connecticut PS12-04: HDACi combined with anthracycline elicits interactions between MHC-II+ triple-negative breast cancer and CD69+CD4+Trm orchestrating synergistic immunotherapy. HDACi联合蒽环类药物引发MHC-II+三阴性乳腺癌与CD69+CD4+Trm协同免疫治疗之间的相互作用讲者：Zehao Wang（复旦大学附属肿瘤医院） ▌Session 14: Brain Metastasis（脑转移）时间：12月13日7:00–8:30 am 地点：Stars at Night 3-4 主持人：William Gradishar, Northwestern University Feinberg School of Medicine, Chicago, Illinois PS14-02: A Prospective Phase II Trial of Hypofractionated Stereotactic Radiotherapy (FSRT) for Patients with 1-10 Brain Metastases from Breast Cancer. 一项前瞻性II期试验，1～10个乳腺癌脑转移患者采用大分割立体定向放疗（FSRT）讲者：Jin Meng（上海交通大学附属第六人民医院） PS14-03: Updated analyses from a Phase I study of the brain-penetrant oral SERD- SIM0270 in patients with ER-positive,HER2-negative advanced breast cancer. 脑渗透性口服SERD- SIM0270治疗ER阳性/HER2阴性晚期乳腺癌患者的I期研究的最新分析讲者：张清媛（哈尔滨医科大学附属肿瘤医院） PS14-04: SIM0270, a brain-penetrant oral SERD, in combination with everolimus in patients with ER+/HER2- advanced breast cancer: the phase Ib study. SIM0270，一种脑渗透性口服SERD，联合依维莫司在ER+/HER2-晚期乳腺癌患者中的Ⅰb期研究讲者：张剑（复旦大学附属肿瘤医院） Year in Review 时间：12月13日3:00 – 5:00 pm 地点：Stars at Night 1-2 主持人：Moderators: Carlos Arteaga, UT Southwestern Medical Center, Dallas, Texas; and Virginia Kaklamani, UT Health Mays Cancer Center, San Antonio, Texas Early Breast Cancer Updates 早期乳腺癌最新进展讲者：Janice Tsang（中国香港大学）（来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床2期临床结果临床3期

2024-11-05

·ioncology

SABCS 2024丨乳腺癌领域年终盛典将至，重磅研究汇总！

点击蓝字，关注我们编者按：第47届圣安东尼奥乳腺癌研讨会（SABCS）将于当地时间2024年12月10日至13日在美国得克萨斯州圣安东尼奥举行。日前，官网已公布摘要题目，肿瘤瞭望特将Late-Breaking Oral Presentations、General Session、Rapid Fire、Poster Spotlight Sessions等环节口头报告内容进行整理，敬请关注！ Late-Breaking Oral Presentations 时间：12月10日6:00 – 7:00 pm 地点：Stars at Night 1-2 主持人：Rita Nanda, University of Chicago Medicine, Chicago, Illinois LB1-01: Long-term effects of the omission of immediate surgery in operable breast cancer, or reduction of surgical extent: patient-level meta-analysis of the four randomised trials among 2,514 women. 可手术乳腺癌中省略即刻手术或缩小手术范围的长期影响：基于2514名女性的四项随机试验患者层面的荟萃分析讲者：Robert Hills, University of Oxford, Oxford, United Kingdom LB1-02: MARGOT/TBCRC052: A randomized phase II trial comparing neoadjuvant paclitaxel/margetuximab/pertuzumab (TMP) vs paclitaxel/trastuzumab/pertuzumab (THP) in patients (pts) with stage II-III HER2+ breast cancer. MARGOT/TBCRC052：一项随机II期临床试验，比较II-III期HER2阳性乳腺癌患者中新辅助治疗帕妥珠单抗/马吉妥昔单抗/紫杉醇（TMP）vs帕妥珠单抗/曲妥珠单抗/紫杉醇（THP）的疗效讲者：Adrienne Waks, Dana-Farber Cancer Institute, Boston, Massachusetts LB1-03: Primary results of the randomised Phase III trial comparing first-line ET plus palbociclib vs standard mono-chemotherapy in women with high risk HER2-/HR+ metastatic breast cancer and indication for chemotherapy - PADMA study. PADMA研究：比较高危HR+/HER2-转移性乳腺癌女性患者一线ET联合哌柏西利vs标准单药化疗的随机III期试验的主要结果讲者：Sibylle Loibl, German Cooperative Group, Neu-Isenburg, Germany LB1-04: Efficacy and safety of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) by pace of disease progression on prior endocrine-based therapy: additional analysis from DESTINY-Breast06. 基于既往内分泌治疗的疾病进展速度，比较德曲妥珠单抗（T-DXd） vs医生选择的化疗（TPC）的疗效与安全性：来自DESTINY-Breast06的额外分析讲者：Aditya Bardia, UCLA David Geffen School of Medicine, Los Angeles, California LB1-05: ROSC (Neo)adjuvant nab-PAC weekly vs sb-PAC q2w, followed by EC q2w, in genomically or clinically high-risk HR+/HER- early breast cancer according to ET-response: final survival results from the WSG ADAPT-HR+/HER2- chemotherapy-trial. 在遗传或临床高危HR+/HER2-早期乳腺癌中，根据ET反应（新）辅助nab-PAC周疗 vs 每2周1次sb-PAC，随后每2周1次EC：WSG ADAPT-HR+/HER2-化疗试验最终生存结果讲者：Sherko Kuemmel, German Medical Institute, Limassol, Germany LB1-06: Primary results of SOLTI VALENTINE: neoadjuvant randomized phase II trial of HER3-DXd alone or in combination with letrozole for high-risk hormone receptor positive (HR+)/HER2-negative (neg) early breast cancer (EBC). SOLTI VALENTINE研究的主要结果：针对高风险HR+/HER2-早期乳腺癌（EBC），比较单独使用HER3-DXd或联合使用来曲唑新辅助治疗的随机II期试验讲者：Mafalda Oliveira, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain LB1-07: Exploratory Biomarker Analysis of the Phase 3 KEYNOTE-522 Study of Neoadjuvant Pembrolizumab or Placebo Plus Chemotherapy Followed by Adjuvant Pembrolizumab or Placebo for Early-Stage TNBC. 3期KEYNOTE-522研究生物标志物探索性分析：对早期TNBC患者用帕博利珠单抗或安慰剂联合化疗进行新辅助治疗，随后用帕博利珠单抗或安慰剂进行辅助治疗讲者：Joyce O’Shaughnessy, Baylor-Sammons Cancer Center, Dallas, Texas General Session 1 时间：12月11日9:15 – 11:30 am 地点：Hall 1 GS1-01: Imlunestrant, an Oral Selective Estrogen Receptor Degrader (SERD), as Monotherapy and Combined with Abemaciclib, for Patients w/ ER+, HER2- Advanced Breast Cancer (ABC), Pretreated w/ Endocrine Therapy (ET): Results of the Phase 3 EMBER-3 trial. 口服选择性雌激素受体降解剂（SERD）Imlunestrant单药治疗及联合阿贝西利治疗既往接受内分泌治疗（ET）的雌激素受体阳性（ER+）、人表皮生长因子受体2阴性（HER2-）晚期乳腺癌（ABC）患者的疗效：III期EMBER-3研究结果讲者：Komal Jhaveri, Memorial Sloan Kettering Cancer Center, New York, New York GS1-03: Pyrotinib or placebo in combination with trastuzumab and docetaxel for untreated HER2-positive metastatic breast cancer (mBC): prespecified final analysis of progression-free survival (PFS) of the phase 3 PHILA trial. 吡咯替尼或安慰剂联合曲妥珠单抗和多西他赛用于未接受过治疗的HER2阳性转移性乳腺癌（mBC）：III期PHILA试验预设的无进展生存期（PFS）最终分析讲者：徐兵河（中国医学科学院肿瘤医院） GS1-04: HER2-Directed Antibody-Drug Conjugate SHR-A1811 in the Neoadjuvant Treatment of HER2-positive Early Breast Cancer: a Prospective, Randomized, Open-label, Phase 2 Trial. 靶向HER2的抗体-药物偶联物SHR-A1811用于HER2阳性早期乳腺癌的新辅助治疗：一项前瞻性、随机、开放标签的2期试验讲者：李俊杰（复旦大学附属肿瘤医院） GS1-06: PRO B – a superiority randomized controlled trial evaluating the effects of symptom monitoring in metastatic breast cancer patients. PRO B ——一项评估转移性乳腺癌患者症状监测效果的优效性随机对照试验讲者：Maria Margarete Karsten, Charité-Universitätsmedizin, Berlin GS1-08: Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: results from an international cohort study. 年轻乳腺癌患者中BRCA携带者接受降低风险性手术与生存期之间的关联：一项国际队列研究结果讲者：Matteo Lambertini, University of Genova, Genova, Italy GS1-09: OlympiA- Phase 3, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients w/ germline BRCA1/BRCA2 pathogenic variants & high risk HER2-negative primary breast cancer; longer term follow. OlympiA长期随访——一项针对携带胚系BRCA1/BRCA2致病性变异且高危HER2阴性原发性乳腺癌患者，在（新）辅助化疗后使用辅助奥拉帕利（olaparib）的III期、多中心、随机、安慰剂对照试验讲者：Judy Garber, Dana-Farber Cancer Institute, Boston, Massachusetts Rapid Fire 1 时间：12月11日12:00 – 12:50 pm 地点：Stars at Night 1-2 主持人：Moderator: Shom Goel, University of Melbourne Peter MacCallum Cancer Centre RF1-01: Effect of a weight loss intervention (WLI) on metabolic and inflammatory biomarkers in women with obesity and breast cancer: Results from the Breast Cancer Weight Loss (BWEL) Trial (Alliance). 减重干预（WLI）对肥胖合并乳腺癌女性的代谢和炎症生物标志物的影响：乳腺癌减重（BWEL）试验（Alliance）的结果讲者：Jennifer Ligibel, Dana-Farber Cancer Institute, Boston, Massachusetts RF1-02: Palbociclib plus letrozole versus weekly paclitaxel, both in combination w/ trastuzumab plus pertuzumab, as neoadjuvant treatment for patients w/ HR+/HER2+ early breast cancer: primary results from the randomized phase II TOUCH trial (IBCSG 55-17). 哌柏西利联合来曲唑对比周疗紫杉醇，两者均与曲妥珠单抗和帕妥珠单抗联用，作为HR+/HER2+早期乳腺癌患者的新辅助治疗：来自II期TOUCH随机试验（IBCSG 55-17）的主要结果讲者：Luca Malorni, USL Toscana Centro, Hospital of Prato, Prato, Italy RF1-03: Three-year event-free survival (EFS) of the multicenter phase II TRAIN-3 study evaluating image-guided optimization of neoadjuvant chemotherapy duration in stage II and III HER2-positive breast cancer (BOOG 2018-01). 多中心II期TRAIN-3研究评估了II期和III期HER2阳性乳腺癌（BOOG 2018-01）中基于影像引导的新辅助化疗持续时间优化的三年无事件生存率（EFS）讲者：Fleur Louis, Antoni van Leeuwenhoekziekenhuis, Amsterdam, Netherlands RF1-04: Long-Term Follow-up and updated analysis from S0221, Comparing Alternative Dose-Schedules of Adjuvant Anthracycline/Taxane Therapy in High-Risk Early Breast Cancer. S0221研究长期随访与更新分析：比较蒽环类/紫杉类辅助治疗高危早期乳腺癌的替代剂量方案讲者：Azka Ali, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois RF1-05: DNA methylation patterns are similar in benign tissue from ipsilateral and contralateral breast while different from matched breast cancer, and healthy controls. 同侧与对侧乳房的良性组织中的DNA甲基化模式相似，但与配对的乳腺癌组织和健康对照组存在差异讲者：Saya Dennis, Northwestern University Feinberg School of Medicine, Chicago, Illinois RF1-06: Association of polygenic-based breast cancer risk prediction with patient management. 基于多基因的乳腺癌风险预测与患者管理的相关性讲者：Katie Johansen Taber, Myriad Genetics, San Francisco, California RF1-07: Multifactor analysis for pathologic complete response (pCR) in a chemotherapy-free regimen of durvalumab, trastuzumab, and pertuzumab (DTP Trial) in HER2-enriched early breast cancer. 在HER2过表达的早期乳腺癌中，不含化疗的度伐利尤单抗、曲妥珠单抗和帕妥珠单抗方案（DTP研究）的病理完全缓解（pCR）的多因素分析讲者：Bojana Stefanovska, UT Health Science Center, San Antonio, Texas General Session 2 时间：12月12日9:00–11:45 am 地点：Hall 1 GS2-01: Exclusive endocrine therapy or radiation therapy in women aged 70+ years with luminal-like early breast cancer (EUROPA): preplanned interim analysis of a randomized phase 3 trial. 随机3期EUROPA研究预先计划的期中分析：70岁以上luminal型早期乳腺癌女性患者单纯内分泌治疗或放疗的疗效讲者：Icro Meattini, University of Florence, Florence, Italy GS2-02: Impact of Tamoxifen Only after Breast Conservation Surgery for "Good Risk" Duct Carcinoma in Situ: Results from the NRG Oncology/RTOG 9804 and ECOG-ACRIN E5194 Trial “低风险”原位导管癌保乳术后仅采用他莫昔芬治疗的影响：NRG Oncology/RTOG 9804和ECOG-ACRIN E5194试验的结果讲者：Jean Wright, University of North Carolina School of Medicine, Chapel Hill, North Carolina GS2-03: Does postmastectomy radiotherapy in 'intermediate-risk' breast cancer impact overall survival? 10-year results of the BIG 2-04 MRC SUPREMO randomised trial: on behalf of the SUPREMO trial investigators. “中危”乳腺癌患者术后放疗是否影响总生存期？BIG 2-04 MRC SUPREMO随机试验10年结果：代表SUPREMO试验研究者讲者：Ian Kunkler, Edinburgh Cancer Centre, University of Edinburgh, Edinburgh, Scotland GS2-05: Early Oncologic Outcomes Following Active Monitoring or Surgery (+/- Radiation) for Low Risk DCIS: the Comparing an Operation to Monitoring, with or without Endocrine Therapy (COMET) Study (AFT-25). 低危导管原位癌（DCIS）患者主动监测或手术（±放疗）后的早期肿瘤学结局：比较手术与监测伴或不伴内分泌治疗（COMET）研究（AFT-25）讲者：Eun-Sil Hwang, Duke University School of Medicine, Durham, North Carolina GS2-06: Patient Reported Outcomes Following Active Monitoring or Surgery (+/- Radiation) for Low Risk DCIS in the Comparing an Operation to Monitoring, with or without Endocrine Therapy (COMET) Study (AFT-25). 低危导管原位癌（DCIS）患者主动监测或手术（±放疗）后的患者报告结局：比较手术与监测伴或不伴内分泌治疗（COMET）研究（AFT-25）讲者：Ann Partridge, Dana-Farber Cancer Institute, Boston, Massachusetts GS2-07: No axillary surgery versus axillary sentinel lymph node biopsy in patients with early invasive breast cancer and breast-conserving surgery: Final primary results of the Intergroup-Sentinel-Mamma (INSEMA) trial. 早期浸润性乳腺癌患者不接受腋窝手术vs接受保乳手术的腋窝前哨淋巴结活检比较：INSEMA（intergroup sentinel - mamma）试验的最终主要结果讲者：Toralf Reimer, Universitätsmedizin Rostock, Rostock, Germany GS2-09: Overweight, obesity and prognosis in 206,904 women in the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) database. 早期乳腺癌试验协作组（Early Breast Cancer trials’Collaborative Group，EBCTCG）数据库中206904名女性的超重、肥胖和预后情况讲者：Hongchao Pan, University of Oxford, Oxford, United Kingdom GS2-10: A long-term image-derived AI risk model for primary prevention of breast cancer. 用于乳腺癌一级预防的基于长期图像衍生的AI风险模型讲者：Mikael Eriksson, Karolinska Institutet, Solna, Sweden GS2-11: APOBEC3 mutagenesis induces resistance-promoting genomic alterations in breast cancer. APOBEC3突变诱导乳腺癌中促进耐药的基因组改变讲者：Avantika Gupta, Memorial Sloan Kettering Cancer Center, New York, New York Rapid Fire 2 时间：12月12日12:00 – 12:50 pm 地点：Hall 1 主持人：Carlos Arteaga, UT Southwestern, Dallas, Texas RF2-01: Factors Influencing Additional Nodal Disease and Pathologic Nodal Upstaging with Axillary Dissection in Patients with Residual Node-Positive Breast Cancer After Neoadjuvant Chemotherapy Enrolled on Alliance A011202 Clinical Trial. Alliance A011202临床试验纳入的新辅助化疗后残留淋巴结阳性乳腺癌患者中，腋窝清扫术对额外淋巴结病变和病理性淋巴结分期上调的影响因素讲者：Judy Boughey, Mayo Clinic, Rochester, Minnesota RF2-02: Axillary surgery after neoadjuvant systemic therapy (NST) for early-stage breast cancer – Treatment algorithms and prognostic impact of residual micrometastases in five neoadjuvant studies. 早期乳腺癌新辅助全身治疗（NST）后的腋窝手术——5项新辅助治疗研究中残留微转移的治疗路径和预后影响讲者：Johannes Holtschmidt, VP Medicine & Research GBG Forschungs GmbH RF2-03: Diagnostic performance of axillary ultrasound after neoadjuvant chemotherapy in initially node-positive breast cancer patients – results from the prospective AXSANA registry trial (NCT04373655). 初诊淋巴结阳性乳腺癌患者新辅助化疗后行腋窝超声的诊断效能——来自前瞻性AXSANA注册试验（NCT04373655）的结果讲者：Steffi Hartmann, University of Rostock, Rostock, Germany RF2-04: Ultrahypofractionated versus conventional fractionated sequential boost after whole-breast radiation therapy in breast cancer patients. One-year cosmetic outcomes of a randomized, controlled, phase 3 trial (ULTIMO). 乳腺癌患者全乳放疗后超大分割vs常规分割序贯加量疗效对比：一项随机、对照、3期试验（ULTIMO）1年美容效果讲者：Melanie Machiels, Universiteit Antwerpen, Antwerp, Belgium RF2-05: Validation of the association between TILs, ER status and benefit of radiotherapy in node positive, breast cancer patients: a DBCG study. DBCG研究：验证TILs、ER状态与淋巴结阳性乳腺癌患者放疗获益之间的关系讲者：Demet Özcan, Aarhus University Hospital, Aarhus, Denmark RF2-06: A Nationwide Double-Blind Phase III RCT Comparing Olanzapine and Prochlorperazine for Refractory Chemotherapy-Induced Nausea in NCORP Community Practices. 一项全国性、双盲、III期、随机对照试验（RCT），比较NCORP社区实践中奥氮平和丙氯拉嗪治疗化疗导致的难治性恶心讲者：Luke Peppone, University of Rochester Medical Center, Rochester, New York General Session 3 时间：12月13日9:00–11:45 am 地点：Hall 1 GS3-01: Circulating tumor DNA surveillance in ZEST, a randomized, phase 3, double-blind study of niraparib or placebo in patients w/ triple-negative breast cancer or HER2+ BRCA-mutated breast cancer with molecular residual disease after definitive therapy. ZEST是一项随机、3期、双盲研究，在尼拉帕利或安慰剂进行根治性治疗后有分子残留病变的三阴性乳腺癌或HER2+ BRCA突变乳腺癌患者中对循环肿瘤DNA进行监测。讲者：Nicholas Turner, Ralph Lauren Centre for Breast Cancer Research, London, United Kingdom GS3-03: Impact of Anthracyclines in High Genomic Risk Node-Negative HR+/HER2- Breast Cancer. 蒽环类药物对高基因组风险淋巴结阴性HR+/HER2-乳腺癌的影响讲者：Nan Chen, University of Chicago Medicine, Chicago, Illinois GS3-04: (Neo)adjuvant nab-PAC weekly vs sb-PAC q2w, followed by EC q2w, in genomically or clinically high-risk HR+/HER2- early breast cancer according to ET-response: final survival results from the WSG ADAPT-HR+/HER2- chemotherapy-trial. 在遗传或临床高危HR+/HER2-早期乳腺癌中，根据ET反应（新）辅助nab-PAC周疗 vs 每2周1次sb-PAC，随后每2周1次EC：WSG ADAPT-HR+/HER2-化疗试验最终生存结果讲者：Sherko Kuemmel, German Medical Institute, Berlin, Germany GS3-05: NSABP B-59/GBG-96-GeparDouze: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy with atezolizumab or placebo followed by adjuvant atezolizumab or placebo in patients with Stage II and III triple-negative breast cancer. NSABP B-59/GBG-96-GeparDouze：一项针对II期和III期三阴性乳腺癌患者的随机双盲III期临床试验，比较新辅助化疗联合阿替利珠单抗或安慰剂，随后辅助使用阿替利珠单抗或安慰剂的效果讲者：Charles Geyer, University of Pittsburgh, Pittsburgh, Pennsylvania GS3-06: Neoadjuvant camrelizumab plus chemotherapy (chemo) for early or locally advanced triple-negative breast cancer (TNBC): a randomized, double-blind, phase 3 trial. 卡瑞利珠单抗联合化疗（chemo）新辅助治疗早期或局部晚期三阴性乳腺癌（TNBC）：一项随机、双盲、3期试验讲者：邵志敏（复旦大学附属肿瘤医院） GS3-08: In situ detection of individual classical MHC-I gene products in breast cancer identifies gene- and subtype-specific biased antigen presentation loss. 在乳腺癌中原位检测单个经典MHC-I基因产物，可识别出基因和亚型特异性的特异性抗原呈递缺失讲者：Paula Gonzalez-Ericsson, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee GS3-09: Multimodal integration of real world clinical and genomic data for the prediction of CDK4/6 inhibitors outcomes in patients with HR+/HER2- metastatic breast cancer. 真实世界临床和基因组数据的多模态整合用于预测CDK4/6抑制剂在HR+/HER2-转移性乳腺癌患者中的结局讲者：Enrico Moiso, Memorial Sloan Kettering Cancer Center, New York, New York GS3-10: Paired DNA and RNA analysis of CALGB 40603 (Alliance) reveals insights into the molecular and prognostic landscape of stage II-III triple-negative breast cancer. 配对的DNA和RNA分析CALGB 40603（Alliance）揭示了II-III期三阴性乳腺癌的分子和预后特征讲者：Brooke Felsheim, UNC School of Medicine, Chapel Hill, North Carolina Rapid Fire 3 时间：12月13日12:00 – 12:50 pm 地点：Hall 1 主持人：Peter Fasching, University Hospital Erlangen and Comprehensive Cancer Center Erlangen-EMN, Germany RF3-01: TBCRC 056: A phase II study of neoadjuvant niraparib with dostarlimab for patients with BRCA- or PALB2-mutated breast cancer: Results from the ER+/HER2- cohort. TBCRC 056研究ER+/HER2-队列的结果：一项尼拉帕利联合dostarlimab新辅助治疗BRCA突变或PALB2突变乳腺癌患者的II期研究讲者：Erica Mayer, Dana-Farber Cancer Institute, Boston, Massachusetts RF3-02: Efficacy of adjuvant avelumab by PD-L1, tumor infiltrating lymphocytes and residual cancer burden in high-risk triple negative breast cancer: secondary and exploratory endpoints of the phase III A-BRAVE trial. 基于PD-L1、肿瘤浸润淋巴细胞和残余肿瘤负荷对高危三阴性乳腺癌进行阿维鲁单抗辅助治疗的疗效：III期A-BRAVE研究的次要和探索性终点讲者：Maria Vittoria Dieci, University of Padua, Padua, Italy RF3-03: Nivolumab + Ipilimumab (NIVO+IPI) compared to capecitabine for triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy – Final results of BreastImmune-03, a multicenter randomized open-label phase II trial. 纳武利尤单抗+伊匹木单抗（NIVO+IPI）与卡培他滨在新辅助化疗后有残留病变的三阴性乳腺癌患者中的疗效比较——多中心随机开放标签II期试验BreastImmune-03的最终结果讲者：Olivier Trédan, Centre Lèon Bèrard, Lyon, France RF3-04: NRG-BR004: A Randomized, Double-blind, Phase III Trial of Taxane/Trastuzumab/Pertuzumab with Atezolizumab or Placebo in First-line HER2-positive Metastatic Breast Cancer. NRG-BR004：紫杉烷/曲妥珠单抗/帕妥珠单抗联合阿替利珠单抗或安慰剂一线治疗HER2阳性转移性乳腺癌的随机、双盲、III期试验讲者：Vicente Valero, MD Anderson Cancer Center, Houston, Texas RF3-05: A Phase 2 Study of Neoadjuvant HER2-targeted Therapy +/- Immunotherapy with Pembrolizumab (neoHIP). 新辅助HER2靶向治疗±帕博利珠单抗免疫治疗的2期研究（neoHIP）讲者：Heather McArthur, UT Southwestern Medical Center, Dallas, Texas RF3-06: Mepitel Film for the Reduction of Radiation Dermatitis in Post-mastectomy Radiation Therapy: Results from Alliance A221803: A Multicenter Phase III Randomized Clinical Trial Mepitel贴膜在减少乳腺癌术后放疗所致放射性皮炎中的应用：Alliance A221803多中心III期随机临床试验结果讲者：Kimberly Corbin, Mayo Clinic, Rochester, Minnesota RF3-07: ROSCO:Response to Optimal Selection of neoadjuvant Chemotherapy in Operable breast cancer: A randomised phase III, stratified biomarker trial of neoadjuvant 5-Fluorouracil, Epirubicin & Cyclophosphamide vs Docetaxel & Cyclophosphamide chemotherapy. ROSCO研究：随机III期、分层生物标志物试验，比较新辅助5-氟尿嘧啶、表柔比星与环磷酰胺vs多西他赛和环磷酰胺化疗方案，评估可手术乳腺癌新辅助化疗最优选择反应。讲者：Daniel Rea, University of Birmingham, Birmingham, United Kingdom Poster Spotlight Sessions ▌Concurrent Poster Spotlight Sessions 1, 3-5, 7 Session 1: New Insights into Immune Biomarkers（免疫生物标志物的新见解）时间：12月11日7:00 – 8:30 am 地点：Room 221ABC 主持人：David Rimm, Yale University Session 3: Highlights on Novel Therapeutics（新型治疗亮点）时间：12月11日7:00 – 8:30 am 地点：Stars at Night 1-2 主持人：Sara Tolaney, Dana-Farber Cancer Institute Session 4: Prediction of Chemotherapy Response（化疗疗效预测）时间：12月11日7:00 – 8:30 am 地点：Stars at Night 3-4 主持人：Sherene Loi, Peter Macallum Cancer Centre Session 5: The Heart of the Matter - Improving Adverse Effects（核心问题-改善不良反应）时间：12月11日7:00 – 8:30 am 地点：Hemisfair Ballroom 3 主持人：Anne Blaes, Masonic Cancer Center University of Minnesota Session 7: Targeting the ER and PI3K pathway: Novel drugs and combinations（靶向ER和PI3K通路：新型药物和组合）时间：12月11日7:00 – 8:30 am 地点：Hemisfair Ballroom 1-2 主持人：Shom Goel, Peter MacCallum Cancer Centre ▌Concurrent Poster Spotlight Sessions 2, 6, 8, 9 and 15 Session 2: Personalizing CDK 4/6 inhibitor therapy for patients with Metastatic Breast Cancer: Survival, QOL and biomarkers（转移性乳腺癌患者的个体化CDK 4/6抑制剂治疗：生存期、生活质量和生物标志物）时间：12月12日7:00 – 8:30 am 地点：Hemisfair Ballroom 1-2 主持人：Lisa Carey, Lineberger Comprehensive Cancer Center University of North Carolina Session 6: Locoregional Therapy（局部区域治疗）时间：12月12日7:00 – 8:30 am 地点：Room 221ABC 主持人：Mylin Torres, Winshop Cancer Institute of Emory University Session 8: Novel HER2 Therapeutics（新型HER2治疗）时间：12月12日7:00 – 8:30 am 地点：Stars at Night 1-2 主持人：Ian Krop, Yale School of Medicine Session 9: ctDNA uses for Minimal Residual Disease testing, tumor evolution, and novel technologies（ctDNA用于微小残留病检测、肿瘤进化和新技术）时间：12月12日7:00 – 8:30 am 地点：Stars at Night 3-4 主持人：Charles Perou, Lineberger Comprehensive Cancer Center University of North Carolina Session 15: Survivorship – Biomarker predictors and other survival-associated factors（生存-生物标志物预测和其他生存相关因素）时间：12月12日7:00 – 8:30 am 地点：Room 221ABC 主持人：Lindsay Peterson, Washington University Siteman Cancer Center, St. Louis, Missouri ▌Concurrent Poster Spotlight Sessions 10-14 Session 10: Addressing Racial Disparities in Breast Cancer Outcomes（探讨乳腺癌结局的种族差异）时间：12月13日7:00 – 8:30 am 地点：Hemisfair Ballroom 3 主持人：Yara Abdou, University of North Carolina School of Medicine Session 11: Imaging to Guide Breast Cancer Treatment – Molecular Imaging and AI（影像学指导乳腺癌治疗——分子影像学和人工智能）时间：12月13日7:00 – 8:30 am 地点：Hemisfair Ballroom 1-2 主持人：David Mankoff, Perelman School of Medicine University of Pennsylvania Session 12: Immunobiology Impact on Therapeutic Efficacy（免疫生物学对治疗效果的影响）时间：12月13日7:00 – 8:30 am 地点：Room 221ABC 主持人：Lajos Pusztai, Yale School of Medicine, New Haven, Connecticut Session 13: Molecular determinants of therapeutic response and resistance - Spotight on CDK 4/6i and ADCs （治疗反应和耐药的分子决定因素——聚焦CDK4/6i和ADCs）时间：12月13日7:00 – 8:30 am 地点：Stars at Night 1-2 主持人：Aditya Bardia, UCLA David Geffen School of Medicine, Los Angeles, California Session 14: Brain Metastasis（脑转移）时间：12月13日7:00–8:30 am 地点：Stars at Night 3-4 主持人：William Gradishar, Northwestern University Feinberg School of Medicine, Chicago, Illinois （来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床结果临床2期抗体药物偶联物

2024-11-04

·BiG生物创新社

ADC 药物回顾、现状及未来方向

作者｜ momo ADC是肿瘤领域发展最快的治疗方式之一，目前已有15种ADC获批，超过210种正在进行临床试验。近年来，ADC的药物研发进入百花齐放阶段，特别是在HER2、EGFR、Trop2、CLDN18.2、Nectin-4等靶点上展示出显著的疗效和良好的安全性，联合用药，双抗ADC成果显著，为患者提供了更多的治疗选择。随着技术的不断进步和创新，ADC疗法在癌症治疗领域的应用前景十分广阔。 01 ADC 药物：癌症治疗的 “魔法子弹” 抗体药物偶联物（Antibody drug conjugates， ADC）被称为癌症治疗的“魔法子弹”，它是一种将单克隆抗体与细胞毒性药物通过化学连接子连接而成的新型生物治疗药物。其概念核心在于将抗体的特异性靶向能力和细胞毒性药物的强大杀伤作用相结合。ADC进入血液循环后，其抗体部分能够特异性地识别并结合肿瘤细胞表面的靶抗原，形成ADC - 靶抗原复合物，然后通过细胞的内吞作用将ADC摄入细胞内部。进入细胞后，连接子在特定的细胞内环境下发生裂解，释放出细胞毒性药物，从而对肿瘤细胞产生杀伤作用。这种设计旨在实现对肿瘤细胞的精准打击，减少对正常细胞的损害，提高癌症治疗的有效性和安全性。图1.ADC药物的结构特点和作用机制 ADC药物开发需综合考虑多个关键因素。首先是靶点选择，要注重其在肿瘤细胞的特异性高表达及与肿瘤生物学过程的相关性；抗体设计方面，需确保低免疫原性、强特异性、高内化效率和长的半衰期，以实现ADCs在体内的有效传递；连接子设计要兼顾稳定性与可裂解性，还有化学性质的兼容性，同时应避免引起ADC聚集，防止在血液中过早释放有效载荷，并在目标位置精确释放活性药物；细胞毒性药物要确保在生理条件下表现出稳定性，并具有能够与抗体结合的官能团；除了选择抗体、连接子和细胞毒性药物之外，将小分子组分附着到抗体上的方法是成功构建ADCs的关键要素，选择合适的偶联方式，对ADC的稳定性和疗效有显著影响。 02 回顾 ADC 药物发展历程：在挑战中铸就的抗癌传奇 ADC的概念由德国医学家、诺贝尔奖得主Paul Ehrlich在20世纪初首次提出。然而，直至20世纪70年代单克隆抗体问世以及蛋白重组工程技术成熟，ADC的研究才逐渐成为抗体药物研发的热门领域。2000年，惠氏制药研发的Mylotarg获得美国FDA加速批准，用于治疗CD33阳性的急性髓系白血病（AML）患者，此药物成为全球首款商业化的ADC药物。但因临床研究中出现致死性毒性，该药物于2010年撤市，后在2017年经规格调整和补充临床证据后再次获批上市。此后，ADC领域经历了漫长的沉寂期。在这期间的八年内，仅有Adcetris、Kadcyla、Besponsa以及Lumoxiti四款新产品获批，整个ADC市场增长缓慢。2019年成为ADC发展历程中的重要分水岭。仅在这一年，就有Polivy、Padcev、Enhertu三款ADC获批。其中，由第一三共与阿斯利康合作的Enhertu被业内视为“ADC领域急剧回暖最大的催化剂”。Enhertu在Destiny - Breast系列研究中取得了颠覆性成功，显著改善了乳腺癌患者的生存和缓解水平。并且，由于Enhertu对HER2阳性和低表达的肿瘤均具有显著活性，这使得业界更加关注ADC对靶标以外恶性细胞的“旁观者效应”。2019年之后，ADC赛道迎来了Trodelvy、Blenrep、Zynlonta等产品的密集获批，市场规模也随之呈指数增长。然而，ADC 药物市场也面临一些挑战，如企业间合作的终止、潜在的耐药性问题等。但总体而言，其增长趋势明显，市场潜力巨大，在癌症治疗及相关领域的发展值得期待。 03 ADC 药物靶点竞争激烈谁能突出重围？ HER2-ADC 自首个HER2单抗药物获批后，HER2靶点在肿瘤治疗领域就备受关注，至今已经历了二十多年的发展历程。当前，已获批的HER2 ADC药物有恩美曲妥珠单抗、德曲妥珠单抗、维迪西妥单抗三种，此外还有大量HER2 ADC药物正处于临床研究阶段，像恒瑞医药的SHR - A1811和石药集团的DP303c等。在这些药物中，德曲妥珠单抗（DS - 8201，Enhertu）因具备独特的结构和高效的抗肿瘤活性，成为HER2 ADC领域中一项重大突破（图3）。图3.2024 ASCO 最新HER2 靶点ADC药物数据 DS-8201是由第一三公与阿斯利康联合开发的人源化靶向HER2的ADC药物。自2019年首次获批以来，该药已在美国、日本、欧盟、中国多个国家和地区获批上市，适应症领域涵盖 HER2 阳性乳腺癌、HER2 阳性胃癌、HER2 低表达乳腺癌、HER2 突变非小细胞肺癌、HER2 阳性实体瘤。在获批适应症和地区不断扩展的同时，德曲妥珠单抗的销售额也是逐年上涨。2023 年，德曲妥珠单抗全球销售额约3959亿日元（约30亿美元），同比增长约78%（图4）。图4.DS-8201临床试验布局及全球销售收入 Trop2 ADC Trop2 ADC在肺癌领域的发展现状具有多面性。在疗效方面，不同公司的产品在不同亚组人群疗效各异。第一三共和科伦博泰的产品对EGFR阳性和非鳞癌人群疗效佳，但对EGFR野生型或鳞癌患者疗效受限；吉列德的产品在驱动基因突变人群疗效好，对非鳞癌和鳞癌有效性相当。戈沙妥珠单抗、SKB264、Dato - DXd在全球开发进展中领先。临床布局上各公司差异显著。科伦博泰/默沙东临床试验多，依据EGFR突变、PD - L1表达量和临床标准疗法对肺癌人群开展注册研究。第一三共/阿斯利康试验数量也较多，首个三期临床未区分基因和蛋白标志物，联合疗法布局更广，而吉列德试验数量少（图5）。图5.Trop2 ADC药物开发进展 2024年ASCO大会上，科伦博泰二期临床研究OptiTROP - Lung01初步数据亮眼，SKB264联合PD - L1单抗一线治疗驱动基因阴性NSCLC表现优异，低剂量组中位PFS达15个月，相比其他药物更具优势，凸显出SKB264（图6）与肿瘤免疫治疗药物联用在NSCLC领域潜力巨大。图6.SKB264结构 Nectin-4 ADC Nectin - 4 ADC作为一种极具潜力的肿瘤治疗药物，在研发方面取得了显著进展（图7），在国际上，Seagen的Padcev是一款较早受到关注的Nectin - 4 ADC药物，在尿路上皮癌的治疗中取得了一定突破。然而，Padcev存在着如皮肤毒性等不良反应问题，这为后续研发提出了改进方向。国产企业在Nectin - 4 ADC研发中展现出强大的创新能力。迈威生物和石药集团等企业采用了先进的第三代ADC技术。这种技术通过对药物偶联工艺进行优化，大大提高了药物的均一性，减少了副作用。以迈威生物的9MW2821和石药集团的SYS6002为代表，它们各自运用独特的技术实现了更优的疗效和安全性。9MW2821采用的IDDC技术以及SYS6002运用的转氨酶技术，都为药物的性能提升做出了贡献。这些技术使得药物能够更精准地作用于肿瘤细胞，在增强对肿瘤杀伤能力的同时，尽量避免对周围正常细胞的损害，进一步提高了治疗效果和患者的耐受性。从整体发展趋势来看，国产Nectin - 4 ADC前景广阔。随着研发的持续推进，有望在更多的适应症中展现其治疗价值。这不仅将为更多肿瘤患者提供新的治疗选择，也将进一步提升国产药物在国际肿瘤治疗领域的地位，推动全球肿瘤治疗水平的提高。图7.Nectin-4 靶点ADC药物研发进展 CLDN18.2 ADC CLDN18.2 ADC研发进展迅速（图8）。国内众多药企积极参与，其中信达生物的 IBI343、康诺亚与乐普生物合作的 CMG901、礼新医药的 LM - 302等产品已处于临床研究相对后期阶段。例如 IBI343被纳入突破性治疗药物名单，CMG901获得多项国际认定且临床数据表现出可观的客观缓解率和疾病控制率，LM - 302在不同癌症适应证的研究中也显示出较好的效果。此外，恒瑞、石药、德琪、健信等药企的相关产品也都在积极开展临床研究，大量临床数据不断涌现，为后续研发和药物优化提供依据，有望为癌症治疗带来新曙光。图8.CLDN18.2 靶点ADC药物研发进展 04 ADC 药物前瞻：多技术融合，重塑肿瘤治疗格局随着肿瘤学导向的 ADC 药物的快速批准，未来可能会继续沿着现有路径发展，包括更多携带 TOPO1i、微管抑制剂和 DNA 损伤剂的 ADC 药物的研发，对已批准 ADC 药物在未探索适应症中的测试，以及对 ADC 与免疫检查点抑制剂和其他抗癌药物组合的评估。同时，为了实现 “魔法子弹” 的梦想，需要对 ADC 药物进行进一步的创新设计。这包括对 ADC 分子特征的精细调整，如通过选择具有不同效力和作用机制的细胞毒性分子、调整药物与抗体的比例以及链接技术等，以提高药物的活性并降低毒性。此外，还可以通过联合使用其他药物或采用新的给药策略来优化 ADC 药物的性能。同时，更激进的创新思路包括替换 ADC 的一个或多个组件，如开发双特异性或多特异性 ADC、引入肽掩模、改造抗体的结合特性以及使用更小的分子替代抗体等。尽管 ADC 药物已经取得了显著进展，但我们对其作用机制的理解仍然有限。未来需要进一步深入研究 ADC 药物在体内的作用过程，包括药物的摄取、分布、代谢和排泄等环节，以及药物与靶点和其他生物分子之间的相互作用。这将有助于我们更好地设计和优化 ADC 药物，提高其治疗效果和安全性。参考资料 [1] Fu, Zhiwen et al. “Antibody drug conjugate: the "biological missile" for targeted cancer therapy.” Signal transduction and targeted therapy vol. 7,1 93. 22 Mar. 2022, doi:10.1038/s41392-022-00947-7 [2] Colombo, Raffaele et al. “The Journey of Antibody-Drug Conjugates: Lessons Learned from 40 Years of Development.” Cancer discovery, OF1-OF20. 23 Oct. 2024, doi:10.1158/2159-8290.CD-24-0708 [3] Wenfeng Fang, et al. 2024 ASCO Oral 8502. [4] 中邮证券、西南证券、智慧芽研报共建Biomedical创新生态圈！如何加入BiG会员？

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适应症	最高研发状态	国家/地区	公司	日期
HER2突变型非小细胞肺癌	申请上市	中国	苏州盛迪亚生物医药有限公司	2024-09-14
结直肠癌	临床3期	中国	江苏恒瑞医药股份有限公司	2024-03-01
HER2阳性胃癌	临床3期	中国	江苏恒瑞医药股份有限公司	2024-01-09
HER2阳性胃食管结合部腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2023-12-28
HER2阳性胃食管交界处癌	临床3期	中国	江苏恒瑞医药股份有限公司	2023-12-28
HER2阳性乳腺癌	临床3期	-	江苏恒瑞医药股份有限公司	2023-10-01
HER2低表达乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2023-06-05
HER2阳性转移性乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2022-08-04
不能切除的乳腺癌	临床3期	中国	江苏恒瑞医药股份有限公司	2022-08-04
晚期胃癌	临床2期	中国	江苏恒瑞医药股份有限公司	2024-12-01

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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


NCT04446260 (Pubmed \| J Clin Oncol) 人工标引	临床1期	HER2阳性实体瘤 HER2 Positive	307	SHR-A1811	壓膚齋醖齋鹽築膚築夢(壓壓鬱齋糧餘願鬱繭膚) = 憲艱憲願獵網顧遞憲鹽衊簾鑰糧簾鬱顧鏇夢鏇 (遞網鏇構獵艱憲築餘積 ) 更多	积极	2024-10-10
				SHR-A1811 (HER2-positive breast cancer)	鹽餘糧網積鬱齋醖膚遞(艱選顧鏇製膚齋廠襯顧) = 夢鏇憲顧廠鬱觸積壓鬱齋淵夢壓衊鑰獵鏇鬱窪 (簾製構膚蓋繭網顧衊齋 )
NCT05635487 (MUKDEN 07, ESMO2024) 人工标引	临床2期	HER2阳性乳腺癌新辅助 HR+	29	SHR-A1811 + Pyrotinib (Total)	鹹築鬱壓鑰築網憲鬱鬱(獵選衊淵築膚齋齋淵膚) = 鹹膚憲選網窪鏇襯衊顧糧構鏇淵範觸廠積餘廠 (鬱觸壓範築網蓋顧艱製, 59.1 ~ 91.7) 更多	积极	2024-09-16
				SHR-A1811 4.8 mg/kg+ Pyrotinib 240 mg/day	鹹築鬱壓鑰築網憲鬱鬱(獵選衊淵築膚齋齋淵膚) = 衊鬱醖衊憲餘膚遞鑰鏇糧構鏇淵範觸廠積餘廠 (鬱觸壓範築網蓋顧艱製 ) 更多
NCT04818333 (Pubmed) 人工标引	临床1/2期	HER2突变型非小细胞肺癌二线 ERBB2 Mutation	63	SHR-A1811	積壓淵築壓簾網築齋淵(壓鑰襯餘顧顧壓選膚鹽) = 觸艱獵鑰壓憲襯獵選遞醖鹽窪獵築廠齋簾淵選 (積積鏇選衊簾蓋獵艱膚, 27.0 ~ 57.9) 更多	积极	2024-07-15
NCT04446260 (Pubmed) 人工标引	临床1期	HER2阳性实体瘤 ERBB2 Mutation (Activating) \| HER2 Expression	307	SHR-A1811	願襯顧艱蓋範遞顧淵鬱(製壓遞選糧夢鑰鬱積餘) = decreased neutrophil count (119 [38.8%]) and decreased WBC count (70 [22.8%]). Interstitial lung disease occurred in only eight (2.6%) patients. 簾餘選壓鹹醖鹽鏇襯構 (憲膚糧觸鹹醖鏇膚觸襯 ) 更多	积极	2024-06-20
				SHR-A1811 (HER2-positive breast cancer)
NCT05924256 (ASCO2024) 人工标引	临床2期	唾液腺肿瘤 HER2 Negative \| ERBB2 Amplification \| HER2 Overexpression \| ... 更多	21	SHR-A1811 (HER2 mutation/amplification or HER2 overexpression (IHC 3+ or IHC 2+/ISH+))	願築淵膚鹹獵構顧築淵(簾餘遞選繭齋簾憲鏇衊) = 遞鑰顧鬱齋廠糧願齋壓網醖構鏇蓋選遞淵憲憲 (鏇餘襯膚願選顧憲範鹹 ) 更多	积极	2024-05-24
				rezvilutamide + leuprolide (IHC AR+)	願築淵膚鹹獵構顧築淵(簾餘遞選繭齋簾憲鏇衊) = 窪齋憲壓壓膚鹽憲夢襯網醖構鏇蓋選遞淵憲憲 (鏇餘襯膚願選顧憲範鹹 ) 更多
NCT04513223 (ESMO2023) 人工标引	临床1期	HER2阳性结直肠癌 \| HER2阳性胃癌 \| HER2阳性胃食管结合部腺癌 HER2-expressing	98	SHR-A1811	廠構繭衊範餘蓋遞繭鏇(網鹹夢網鬱積醖繭積衊) = 網積鏇淵願鑰夢繭築衊齋鏇觸範顧鹽壓夢齋築 (壓鹹製顧簾遞壓廠觸艱 ) 更多	积极	2023-10-23
				SHR-A1811 (All GC/GEJ)	廠糧獵繭壓鏇製選壓鏇(鹹繭選鏇蓋願衊襯衊醖) = 簾壓鏇餘積繭鹹鹹醖廠鬱繭齋網窪醖鹽廠簾願 (壓窪醖淵遞選憲憲醖鑰, 71.2 ~ 92.2) 更多
NCT04446260 (ESMO2023) 人工标引	临床1期	晚期恶性实体瘤 HER2	98	SHR-A1811	蓋範艱廠襯廠構選築醖(膚糧顧夢夢簾憲製襯願) = 獵鏇網廠餘憲憲遞蓋構廠衊獵醖壓構獵選糧遞 (範廠鹽憲壓鹹範淵鑰襯 ) 更多	积极	2023-10-23
				SHR-A1811 (HER2 IHC3+)	繭鬱範鏇簾膚願糧積鬱(襯襯蓋遞壓鑰衊壓積衊) = 襯顧憲夢築餘淵顧餘積願鏇觸衊遞選築願積襯 (範觸選醖夢範壓觸繭窪 )
AACR2023 人工标引	临床1期	HER2表达癌症 \| 实体瘤 HER2	250	SHR-A1811	積鏇鑰網製憲獵艱壓構(觸衊鏇鹹憲鏇窪觸觸夢) = 築繭糧製觸襯淵顧憲獵鬱醖鑰鑰選構構窪鏇遞 (衊遞簾積淵醖鏇淵築憲 ) 更多	积极	2023-04-14
				SHR-A1811 (HER2 positive breast cancer)	鹽積餘憲膚簾簾遞壓醖(艱鏇製遞獵窪憲遞觸觸) = 繭淵構獵製膚醖壓糧衊醖簾願觸築獵積構廠憲 (鑰齋鑰簾觸餘淵襯襯網, 72.9 ~ 88.3)
NCT04818333 (AACR2023) 人工标引	临床1/2期	HER2突变型非小细胞肺癌 HER2 Positive	50	SHR-A1811	簾觸蓋獵膚夢鏇衊築觸(構顧夢糧繭鬱糧夢壓簾) = 積選夢顧顧鏇艱簾夢積積衊積衊築壓範餘鹹憲 (鑰構廠窪選遞顧網觸蓋 ) 更多	积极	2023-04-14