更新于：2024-04-26

Lapatinib Ditosylate Hydrate

二甲苯磺酸拉帕替尼

更新于：2024-04-26

概要

概要

基本信息

药物类型

小分子化药

别名

LAPATINIB、Lapatinib ditosilate、LAPATINIB DITOSYLATE

+ [9]

靶点

EGFR x HER2

作用机制

EGFR拮抗剂(表皮生长因子受体erbB1拮抗剂)、HER2拮抗剂(受体蛋白酪氨酸激酶 erbB-2拮抗剂)

治疗领域

肿瘤皮肤和肌肉骨骼疾病消化系统疾病+ [2]

在研适应症

转移性乳腺癌HER2阳性乳腺癌乳腺癌+ [5]

非在研适应症

异戊酸血症腺泡细胞癌腺癌+ [71]

原研机构

GSK Plc

在研机构

葛兰素史克（中国）投资有限公司

Novartis Pharmaceuticals Corp.

Glaxo Group Ltd.

+ [5]

非在研机构

Merck Sharp & Dohme Corp.

National Cancer Institute

Memorial Sloan Kettering Cancer Center

+ [2]

最高研发阶段批准上市

首次获批日期

美国 (2007-03-13),

乳腺癌

最高研发阶段(中国)批准上市

特殊审评加速批准 (美国)、孤儿药 (美国)

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结构

分子式C36H36ClFN4O8S2

InChIKeyDFHHLTRPIUJKPY-UHFFFAOYSA-N

CAS号388082-78-8

关联

351

项与二甲苯磺酸拉帕替尼相关的临床试验

NCT00455039 / Withdrawn临床1/2期IIT

INST 0514C- A Neoadjuvant Phase II Trial of GW572016 in HER2 Overexpressing Breast Cancer Patients: Biologic Correlative Study

Neoadjuvant chemotherapy has become the standard of care for breast cancer patients with large tumors in order to render them operable for mastectomy or, in some cases, for lumpectomy and radiation therapy. Building on this theme, several large hormonal therapies are extensively investigated in the neoadjuvant setting, together with biologic correlates for response and resistance. As a further extension, neoadjuvant therapies with biologic agents are now too, being investigated for biologic evidence of efficacy before large-scale clinical trials of thousands of patients are embarked on. The neoadjuvant setting is especially attractive for these studies for several reasons including early assessment of response to therapy, biopsiable access to the primary tumor, and considerable reduced sample sizes compared to those required in the adjuvant setting. In addition, clinical response to neoadjuvant chemotherapy is a validated surrogate marker for improved survival. It may be used to test the overall efficacy of neoadjuvant treatment regimens and mirrors the effect of therapy on micrometastases setting. In a recent study, good clinical response to neoadjuvant chemotherapy was the only independent variable, by multivariate analysis, associated with decreased risk of death.
GW572016 is a new and promising dual tyrosine kinase inhibitor against HER1/2. Hundreds of patients were treated in phase I and II studies world-wide and results indicate that this reversible, oral small molecule is generally well-tolerated. Studies of neoadjuvant Trastuzumab indicate that HER2 interference leads to significant tumor regression even after 3 weeks of monotherapy. We aim to extend these findings with a novel agent, GW572016 that may be more effective, especially from its in vitro data, and to discover the true response rate to inhibiting HER1/2 signal transduction in breast cancer patients.

开始日期2023-07-31

申办/合作机构

The University of New Mexico

NCT05400902 / Recruiting临床2期IIT

Hepatic Arterial Infusion Chemotherapy Combined With Sintilimab and Bevacizumab in the Treatment of Unresectable Intrahepatic Cholangiocarcinoma: A Prospective, Single-Center, Phase II Study

Primary liver cancer is the sixth most common cancer worldwide, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, of which intrahepatic cholangiocarcinoma accounts for 10%-15%. Surgical resection is the only curative method for ICC, but most patients are diagnosed at an advanced stage, and only 15% of patients can undergo surgical resection. In locally advanced ICC patients without distant metastases, although the tumor was initially assessed as unresectable, these patients may have the opportunity for surgical resection after reducing the size tumor lesion and increasing the remnant liver volume through conversion therapy. The current standard first-line treatment for unresectable ICC is gemcitabine combined with cisplatin, with a median overall survival of only 11.7 months and an ORR of 26.1%. In view of the poor effect of the standard chemotherapy regimen, the NCCN guidelines recommend that patients could participate in clinical study. Hepatic arterial infusion chemotherapy can increase the local blood drug concentration and improve the tumor regression rate. By reducing the dose of systemic chemotherapy drugs concentration, the incidence of adverse reactions can be reduced. Hepatic arterial infusion chemotherapy may be a better choice for locally advanced intrahepatic cholangiocarcinoma. PD-1 immunotherapy combined with targeted therapy is expected to improve the prognosis of patients with intrahepatic cholangiocarcinoma. This study investigates the safety and efficacy of hepatic arterial infusion chemotherapy combined with sintilimab and bevacizumabin the treatment of unresectable ICC.

开始日期2023-05-31

申办/合作机构

中山大学

NCT05290116 / Recruiting临床2期IIT

Hepatic Arterial Infusion Chemotherapy Combined With Tislelizumab and Apatinib in the Treatment of Unresectable Intrahepatic Cholangiocarcinoma: A Prospective, Single-Center, Phase II Study

Primary liver cancer is the sixth most common cancer worldwide, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, of which intrahepatic cholangiocarcinoma accounts for 10%-15%. Surgical resection is the only curative method for ICC, but most patients are diagnosed at an advanced stage, and only 15% of patients can undergo surgical resection. In locally advanced ICC patients without distant metastases, although the tumor was initially assessed as unresectable, these patients may have the opportunity for surgical resection after reducing the size tumor lesion and increasing the remnant liver volume through conversion therapy. The current standard first-line treatment for unresectable ICC is gemcitabine combined with cisplatin, with a median overall survival of only 11.7 months and an ORR of 26.1%. In view of the poor effect of the standard chemotherapy regimen, the NCCN guidelines recommend that patients could participate in clinical study. Hepatic arterial infusion chemotherapy can increase the local blood drug concentration and improve the tumor regression rate. By reducing the dose of systemic chemotherapy drugs concentration, the incidence of adverse reactions can be reduced. Hepatic arterial infusion chemotherapy may be a better choice for locally advanced intrahepatic cholangiocarcinoma. PD-1 immunotherapy combined with targeted therapy is expected to improve the prognosis of patients with intrahepatic cholangiocarcinoma. This study investigates the safety and efficacy of hepatic arterial infusion chemotherapy combined with tislelizumab and apatinib in the treatment of unresectable ICC.

开始日期2022-07-21

申办/合作机构

中山大学

100 项与二甲苯磺酸拉帕替尼相关的临床结果

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100 项与二甲苯磺酸拉帕替尼相关的转化医学

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100 项与二甲苯磺酸拉帕替尼相关的专利（医药）

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2,973

项与二甲苯磺酸拉帕替尼相关的文献（医药）

2024-03-01·European Journal of Pharmacology

Corrigendum to “Lapatinib ditosylate rescues motor deficits in rotenone-intoxicated rats: Potential repurposing of anti-cancer drug as a disease-modifying agent in Parkinson's disease” [Eur. J. Pharmacol. 954 (2023) 175875]

作者: Mansour, Heba M ; Mohamed, Ahmed F ; El-Khatib, Aiman S ; Khattab, Mahmoud M

2024-02-02·The Oncologist

Long-term Outcome Analysis of Pyrotinib in Patients With HER2-Positive Metastatic Breast Cancer and Brain Metastasis: A Real-World Study

Review

作者: Liu, Xiaoran ; Li, Huiping ; Gui, Xinyu ; Yan, Ying ; Song, Guohong ; Liang, Xu ; Di, Lijun

Abstract:

Background:

Pyrotinib is currently approved for the treatment of HER2-positive advanced breast cancer in China. Data on the overall survival (OS) and efficacy in patients with brain metastasis (BM) remain scarce. This study evaluated the effectiveness of pyrotinib in a real-world setting, especially in patients with BM.

Methods:

We reviewed patients with metastatic breast cancer treated with pyrotinib-based therapy between June 2018 and June 2022. Progression-free survival (PFS), OS, objective response rate, and safety were analyzed following the administration of pyrotinib.

Results:

A total of 239 patients were included. The median PFS in patients who received pyrotinib-based therapy as first-line (15/239), second-line (115/239), or third-or-higher-line (109/239) treatment was 14.00, 9.33, and 8.20 months, respectively, and the median OS was not reached, 29.07 and 22.23 months, respectively. The median PFS in patients who pretreated with trastuzumab (214/239), trastuzumab plus pertuzumab (22/239), lapatinib (68/239), or trastuzumab emtansine (14/239) was 9.33, 6.87, 7.20, and 7.20 months, respectively. In 61 patients with BM, the median PFS was 7.50 months, the median central nervous system (CNS)-PFS was 11.17 months, and the median OS was 21.27 months. Furthermore, 19 patients with concomitant brain radiotherapy tended to achieve a longer OS than 42 patients without radiation (34.17 vs. 20.70 months, P = .112).

Conclusions:

Long-term outcomes of pyrotinib-based therapy are promising for patients with HER2-positive metastatic breast cancer in real world and in patients with BM, regardless of the treatment lines and prior anti-HER2 therapies.

Stem Cells

Neuropeptide substance P alters stem cell fate to aid wound healing and promote epidermal stratification through asymmetric stem cell divisions

Article

作者: Sanad, Samia ; Weisenberger, T ; Ghadially, R ; Abegaze, B ; Fassett, M ; AbuElnasr, Taher ; Khalifa, A ; Xiao, T ; Charruyer, A ; Kashem, S W

Abstract:

Loss of sensory innervation delays wound healing and administration of the neuropeptide substance P improves re-epithelialization. Keratinocyte hyperproliferation post-wounding may result from symmetric stem cell (SC) self-renewal, asymmetric SC self-renewal, committed progenitor divisions, or a combination of these. However, the effects of sensory denervation and of neuropeptides on SC proliferation are not known. Here we show that early after wounding both asymmetric and symmetric SC self-renewal increase, without significant committed progenitor (CP) activation. Decreased sensory innervation is associated with a decrease in both SC and CP proliferation. Based on previous work showing that substance P is decreased in capsaicin-treated mice and improves wound healing in normal skin, we examined the effects of substance P on SC and CP proliferation during wound healing. Substance P restored asymmetric SC proliferation in skin with decreased sensory innervation, both at baseline and following wounding. Epidermis with decreased sensory innervation was severely thinned. Consistent with this, substance P-induced asymmetric SC proliferation resulted in increased stratification in skin with both normal and decreased innervation. Lapatinib prevented the substance P-induced increase in asymmetric SC divisions in murine epidermis, as well as the increase in epidermal stratification, suggesting that asymmetric SC divisions are required for epidermal stratification.

127

项与二甲苯磺酸拉帕替尼相关的新闻（医药）

2024-04-25

·BiG生物创新社

ASCO 2024丨这些中国临床专家，将分享最新重磅研究

2024年美国临床肿瘤学会(ASCO)年会将于5月31日到6月4日在芝加哥举办，是世界上规模最大、学术水平最高、最具权威性的临床肿瘤学会议，会议汇集了全球肿瘤学医生和专业人士、患者倡导者、工业界代表和主要媒体，共同探讨当前国际最前沿的研究发现和临床试验成果。ASCO成立于1964年,是世界上最大、最具影响力的肿瘤专业学术组织,致力于癌症的预防、治疗及改善对患者的护理。ASCO在全球150多个国家和地区拥有超过45,000名成员。4月24日晚，ASCO官网公布了本次大会的研究标题，几十余名中国专家将在世界舞台上展示其研究成果，报告涵盖了多个瘤种的最新治疗策略和技术，展示了中国在全球癌症研究中的重要地位和贡献。世易编辑团队精心整理了中国专家们的研究报告，供您参考。全体大会报告Osimertinib (osi) after definitive chemoradiotherapy (CRT) in patients (pts) with unresectable stage (stg) III epidermal growth factor receptor-mutated (EGFRm) NSCLC: Primary results of the phase 3 LAURA study. Abstract: LBA4 · Suresh S. Ramalingam教授，美国埃默里大学Winship癌症研究所· 陆舜教授，上海交通大学附属胸科医院口头报告Lung Cancer—Non-Small Cell MetastaticSacituzumab tirumotecan (SKB264/MK-2870) in combination with KL-A167 (anti-PD-L1) as first-line treatment for patients with advanced NSCLC from the phase II OptiTROP-Lung01 study. Abstract: 8502 · 方文峰教授，中山大学肿瘤防治中心 Ivonescimab combined with chemotherapy in patients with EGFR-mutant non-squamous non-small cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor treatment (HARMONi-A): A randomized, double-blind, multi-center, phase 3 trial. Abstract: 8508 · 张力教授，中山大学肿瘤防治中心 Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers Adjuvant icotinib of 12 months or 6 months versus observation following adjuvant chemotherapy for resected EGFR-mutated stage II–IIIA non-small-cell lung cancer (ICTAN, GASTO1002): A randomized phase 3 trial. Abstract: 8004 ·王思愚教授，中山大学肿瘤防治中心 A phase II randomized trial evaluating consolidative nivolumab in locally advanced non-small cell lung cancer post neoadjuvant chemotherapy plus nivolumab and concurrent chemoradiotherapy (GASTO-1091). Abstract: 8008 · 刘慧教授，中山大学肿瘤防治中心 Taiwan national lung cancer early detection program for heavy smokers and non-smokers with family history of lung cancer. Abstract: 8009 · Pan-Chyr Yang, MD, PhD，台湾大学医学院 Gastrointestinal Cancer—Colorectal and Anal Neoadjuvant treatment of IBI310 (anti-CTLA-4 antibody) plus sintilimab (anti-PD-1 antibody) in patients with microsatellite instability-high/mismatch repair-deficient colorectal cancer: Results from a randomized, open-labeled, phase Ib study. Abstract: 3505 · 徐瑞华教授，中山大学肿瘤防治中心 Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant Phase I study of CN201, a novel CD3xCD19 IgG4 bispecific antibody, in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Abstract: 6505 · 王迎教授，中国医学科学院血液病医院 Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia CLAMP: A phase II prospective study of camrelizumab combined with pegaspargase, etoposide, and high-dose methotrexate in patients with natural killer (NK)/T-cell lymphoma. Abstract: 7002 · 刘涛教授，华中科技大学同济医学院附属协和医院 Tucidinostat plus R-CHOP in previously untreated diffuse large B-cell lymphoma with double expression of MYC and BCL2: An interim analysis from the phase III DEB study. Abstract: LBA7003 · 赵维莅教授，上海交通大学医学院附属瑞金医院 Hematologic Malignancies—Plasma Cell DyscrasiaPhase 3 study results of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) versus VRd for transplant-ineligible patients with newly diagnosed multiple myeloma (IMROZ). Abstract: 7500 ·Thierry Facon, MD，University of Lille, CHU Lille·刘卓刚教授，中国医科大学附属盛京医院Central Nervous System Tumors Efficacy and safety of the vebreltinib in patients with previously treated, secondary glioblastoma/IDH mutant glioblastoma with PTPRZ1-METFUsion GENe (FUGEN): A randomised, multicentre, open-label, phase II/III trial. Abstract: 2003 · Zhaoshi Bao, MD, PhD，首都医科大学附属北京天坛医院 High-dose almonertinib in treatment-naïve EGFR-mutated NSCLC with CNS metastases: Efficacy and biomarker analysis. Abstract: 2007 · 范云教授，浙江省肿瘤医院 SarcomaUpdated efficacy results of olverembatinib (HQP1351) in patients with tyrosine kinase inhibitor (TKI)-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GIST) and paraganglioma. Abstract: 11502 · 邱海波教授，中山大学肿瘤防治中心 Sintilimab, doxorubicin and ifosfamide (AI) as first-line treatment in patients with advanced undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), myxoid liposarcoma (MLPS) and de-differentiated liposarcoma (DDLPS): A single-arm phase 2 trial. Abstract: 11505 · 罗志国教授，复旦大学附属肿瘤医院 ARTEMIS-002: Phase 2 study of HS-20093 in patients with relapsed or refractory osteosarcoma. Abstract: 11507 · 谢璐教授，北京大学人民医院 Head and Neck Cancer Adjuvant PD-1 blockade with camrelizumab in high-risk locoregionally advanced nasopharyngeal carcinoma (DIPPER): A multicenter, open-label, phase 3, randomized controlled trial. Abstract: LBA6000 · 刘需教授，中山大学肿瘤防治中心 Tislelizumab versus placebo combined with induction chemotherapy followed by concurrent chemoradiotherapy and adjuvant tislelizumab or placebo for locoregionally advanced nasopharyngeal carcinoma: Interim analysis of a multicenter, randomized, placebo-controlled, double-blind, phase 3 trial. Abstract: 6001 · 陈秋燕教授，中山大学肿瘤防治中心 Endostar combined with concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone for locoregionally advanced nasopharyngeal carcinoma (LA-NPC): A phase III, prospective, randomised-controlled, multicenter clinical trial. Abstract: 6002 · 康敏教授，广西医科大学第一附属医院 Developmental Therapeutics—ImmunotherapyClaudin18.2-targeted chimeric antigen receptor T cell-therapy for patients with gastrointestinal cancers: Final results of CT041-CG4006 phase 1 trial. Abstract: 2501 · 齐长松教授，北京大学肿瘤医院 A potential best-in-class BCMA-CD19 bispecific CART with advanced safety by self-inhibiting IFNG signaling during CRS. Abstract: 2502 · Lei Xue Efficacy and safety of LM-108, an anti-CCR8 monoclonal antibody, in combination with an anti-PD-1 antibody in patients with gastric cancer: Results from phase 1/2 studies. Abstract: 2504 · Chang Liu, MD，北京大学肿瘤医院Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology Phase I/II first-in-human study to evaluate the safety and efficacy of tissue factor-ADC MRG004A in patients with solid tumors.Abstract: 3002· Wungki Park, MD, MS，美国纪念斯隆凯瑟琳癌症中心· 张剑教授，复旦大学附属肿瘤医院Updated safety and efficacy data of combined KRAS G12C inhibitor (glecirasib, JAB-21822) and SHP2 inhibitor (JAB-3312) in patients with KRAS p.G12C mutated solid tumors. Abstract: 3008 · 赵军教授，北京大学肿瘤医院快速口头摘要报告 Lung Cancer—Non-Small Cell Metastatic A multinational pivotal study of sunvozertinib in platinum pretreated non-small cell lung cancer with EGFR exon 20 insertion mutations: Primary analysis of WU-KONG1 study. Abstract: 8513 · James Chih-Hsin Yang 教授，台大肿瘤中心 Efficacy and safety of taletrectinib in patients with advanced or metastatic ROS1+ non–small cell lung cancer: The phase 2 TRUST-I study. Abstract: 8520 · 李玮教授，同济大学附属上海市肺科医院 Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers Overall survival of adebrelimab plus chemotherapy and sequential thoracic radiotherapy as first-line treatment for extensive-stage small cell lung cancer. Abstract: 8014 · 陈大卫教授，山东省肿瘤医院 Breast Cancer—Metastatic ACE-Breast-02: A pivotal phase II/III trial of ARX788, a novel anti-HER2 antibody-drug conjugate (ADC), versus lapatinib plus capecitabine for HER2+ advanced breast cancer (ABC). Abstract: 1020 · 胡夕春教授，复旦大学附属肿瘤医院 Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary Efficacy and safety of cadonilimab in combination with pulocimab and paclitaxel as second-line therapy in patients with advanced gastric or gastroesophageal junction (G/GEJ) cancer who failed immunochemotherapy: A multicenter, double-blind, randomized trial. Abstract: 4012 · 张小田教授，北京大学肿瘤医院 Phase I study of C-CAR031, a GPC3-specific TGFβRIIDN armored autologous CAR-T, in patients with advanced hepatocellular carcinoma (HCC). Abstract: 4019 · 章琦教授，浙江大学医学院附属第一医院肝胆胰外科 Gastrointestinal Cancer—Colorectal and Anal Total neoadjuvant treatment with long-course radiotherapy versus concurrent chemoradiotherapy in local advanced rectal cancer with high risk factors (TNTCRT): A multicenter, randomized, open-label, phase 3 trial. Abstract: LBA3511 · Xin Wang, MD，四川大学华西医院 Phase I trial of hypoxia-responsive CEA CAR-T cell therapy in patients with heavily pretreated solid tumor via intraperitoneal or intravenous transfusion. Abstract: 3514 · Hangyu Zhang，浙江大学医学院第一附属医院 Three-year disease-free survival after transanal vs. laparoscopic total mesorectal excision for rectal cancer (TaLaR): A randomized clinical trial. Abstract: 3516 · 康亮教授，中山大学附属第六医院 Genitourinary Cancer—Kidney and Bladder Camrelizumab plus apatinib for previously treated advanced adrenocortical carcinoma: A single-arm, open-label, phase 2 trial. Abstract: 4511 · Zhigong Wei，四川大学华西医院 Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant Latest results of a phase 2 study of IMM01 combined with azacitidine (AZA) as the first-line treatment in adults with higher risk myelodysplastic syndromes (MDS). Abstract: 6510 · Wei Yang，中国医科大学附属盛京医院 Safety and efficacy of CD7-CAR-T cell in patients with relapsed/refractory T-lymphoblastic leukemia/lymphoma: Phase I dose-escalation/dose-expansion study. Abstract: 6515 · Lijuan Hu, MD, 北京大学人民医院 Hematologic Malignancies—Plasma Cell Dyscrasia OriCAR-017, a novel GPRC5D-targeting CAR-T, in patients with relapsed/refractory multiple myeloma: Long term follow-up results of phase 1 study (POLARIS). Abstract: 7511 · Shan Fu，浙江大学医学院附属第一医院 Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia Timdarpacept (IMM01) in combination with tislelizumab in prior anti-PD-1 failed classical Hodgkin lymphoma: An open label, multicenter, phase II study (IMM01-04) evaluating safety as well as preliminary anti-tumor activity. Abstract: 7017 · Zhenjiu Wang, MD Gynecologic Cancer Efficacy and safety of sintilimab plus paclitaxel and cisplatin as neoadjuvant therapy for locally advanced cervical cancer: A phase II trial. Abstract: 5512 ·刘继红教授，中山大学肿瘤防治中心 Nimotuzumab plus concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma: The randomized, phase 3 CC3 study. Abstract: 5514 ·王俊杰教授，北京大学第三人民医院 A phase III randomized, double-blinded, placebo-controlled study of suvemcitug combined with chemotherapy for platinum-resistant ovarian cancer (SCORES). Abstract: LBA5516 · 袁光文教授，中国医学科学院肿瘤医院 Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): A final overall survival analysis of a multicenter, open-label, randomized, phase 3 trial. Abstract: 5520 · 臧荣余教授，复旦大学附属中山医院 Head and Neck Cancer Preliminary results of phase I/II study to evaluate safety and efficacy of combination pucotenlimab with epidermal growth factor receptor-ADC (EGFR-ADC) MRG003 in patients with EGFR positive solid tumors. Abstract: 6013 · 阮丹云教授，中山大学肿瘤防治中心 Covalent FAPI PET enables accurate management of medullary thyroid carcinoma: a prospective single-arm comparative clinical trial. Abstract: LBA6018 · Ziren Kong, MD, 中国医学科学院北京协和医学院 Sarcoma A phase II study of anlotinib and an anti-PDL1 antibody in patients with alveolar soft part sarcoma: Results of expansion cohorts. Abstract: 11515 · 刘佳勇教授，北京大学肿瘤医院 Phase 1 study of NB003, a broad-spectrum KIT/PDGFRα inhibitor, in patients with advanced gastrointestinal stromal tumors (GIST). Abstract: 11518 · 李健教授，北京大学肿瘤医院 Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology Results of a phase 1/2 study of MHB088C: A novel B7H3 antibody-drug conjugate (ADC) incorporating a potent DNA topoisomerase I inhibitor in recurrent or metastatic solid tumors. Abstract: 3012 · 沈琳教授，北京大学肿瘤医院 9MW2821, a nectin-4 antibody-drug conjugate (ADC), in patients with advanced solid tumor: Results from a phase 1/2a study. Abstract: 3013 · 张剑教授，复旦大学附属肿瘤医院 Developmental Therapeutics—Immunotherapy Phase I study of GUCY2C CAR-T therapy IM96 in patients with metastatic colorectal cancer. Abstract: 2518 · 齐长松教授，北京大学肿瘤医院 Safety and preliminary efficacy results of IBI389, an anti-CLDN18.2/CD3 bispecific antibody, in patients with solid tumors and gastric or gastro-esophageal tumors: A phase 1 dose escalation and expansion study. Abstract: 2519 · 郑莉教授，四川大学华西医院 Symptom Science and Palliative Care Effect of nurse-led multi-disciplinary treatment on patients with head and neck tumors: A randomized controlled trial. Abstract: 12013 · Jingjing Wang, MD，四川大学华西医院肿瘤中心临床科学研讨会A phase 1/2 study of the TORC1/2 inhibitor onatasertib combined with toripalimab in patients with advanced solid tumors: Cervical cancer cohort. Abstract: 5509 · Hui Xie，德琪医药有限公司临床研发部 KRYSTAL-12: Phase 3 study of adagrasib versus docetaxel in patients with previously treated advanced/metastatic non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation. Abstract: LBA8509 · Tony S. K. Mok 教授，香港大学 Sacituzumab tirumotecan (SKB264/MK-2870) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): Results from the phase III OptiTROP-Breast01 study. Abstract: 104 · 樊英教授，中国医学科学院肿瘤医院 Efficacy of disitamab vedotin (RC48) plus tislelizumab and S-1 as first-line therapy for HER2-overexpressing advanced stomach or gastroesophageal junction adenocarcinoma: A multicenter, single-arm, phase II trial (RCTS). Abstract: 4009 · 刘联教授，山东大学齐鲁医院 A novel and uniquely designed bispecific antibody (LBL-024) against PD-L1 and 4-1BB in patients with advanced malignant tumors and neuroendocrine carcinoma: A report of safety and robust efficacy of LBL-024 monotherapy in phase I/II, first-in-human, open-label, multicenter, dose escalation/expansion study. Abstract: 4010 · 张盼盼医生，北京大学肿瘤医院 Safety and efficacy of IBI389, an anti-CLDN18.2/CD3 bispecific antibody, in patients with advanced pancreatic ductal adenocarcinoma: Preliminary results from a phase 1 study. Abstract: 4011 · 郝继辉教授，天津医科大学肿瘤医院 Neoadjuvant sintilimab and platinum-doublet chemotherapy followed by transoral robotic surgery for HPV-associated resectable oropharyngeal cancer: Single-arm, phase II trial. Abstract: 6011 · 宋明教授，中山大学肿瘤防治中心 BiG 十周年预告本次BiG十周年庆典，将首次分为国内和国际篇章，以原创科学和临床需求为出发点，讨论创新技术平台和创新疗法（PROTACT/分子胶、双抗/ADC、siRNA/ASO、CGT、AI制药）的重大进展和发展前景，十年一药曙光现，大浪淘沙始见金！▼报名参会会议门票：审核制(免费)；含主论坛+分论坛，不含餐；优先biotech/Pharma、临床、院校科学家共建Biomedical创新生态圈！如何加入BiG会员？

ASCO会议临床结果

2024-04-24

·GBIHealth

乳腺癌：细化分型与新药进展

根据世界卫生组织（WHO）国际癌症研究所发布的数据，乳腺癌已在2020年取代肺癌成为全球第一大肿瘤，严重威胁女性健康。在中国，乳腺癌发病率同样位居女性恶性肿瘤之首；且中国乳腺癌患者的发病高峰年龄在45-54岁，比欧美国家提前10年左右。国家卫健委《乳腺癌诊疗指南（2022年版）》和中国抗癌协会《乳腺癌诊治指南与规范（2024年版）》均建议，风险人群应在40岁起接受乳腺癌筛查，高危人群可将筛查起始年龄提前到40岁之前1,2。尽管发病率较高，但乳腺癌也是众多恶性肿瘤中治疗选择较多、预后较好的癌种之一。根据2018年发布的全球癌症生存率变化趋势监测研究报告（CONCORD-3），中国乳腺癌患者在2000-2014年期间的5年生存率为83.2%，是中国5年生存率最高的癌种；但这一数据仍低于美国（90.2%）、澳大利亚（89.5%）、日本（89.4%）等发达国家3。近年来，随着分子机制研究的持续深入和新药研发的不断进展，乳腺癌诊疗领域引入了诸多新理念。以抗体偶联药物（ADC）为代表的创新疗法为广大患者提供了更为精准化、个体化的管理方案，进一步提升了乳腺癌患者的生存预后和生活质量，有望帮助更多患者实现治愈、回归社会生活。01分子分型与系统治疗根据患者是否有基因突变，激素受体和细胞分子状态，乳腺癌可分为HER2阴性（Luminal A和Luminal B）、HER2阳性（HER2+/HR-和HER2+/HR+）和三阴性乳腺癌（TNBC）。来源：CSCO乳腺癌诊疗指南HR+/HER2-的Luminal型是最普遍的乳腺癌亚型，占比高达70%。HR+/HER2-乳腺癌大多预后良好，I期5年生存率可达99%，转移性患者中位OS可达4~5年4。HR+/HER2-乳腺癌通常需接受内分泌治疗，并根据绝经状态选择不同的口服抗雌激素药物，例如：他莫昔芬等ER调节剂对绝经前和绝经后妇女均有效；来曲唑等芳香酶抑制剂仅用于绝经后患者。绝经前后的晚期患者均可考虑在内分泌治疗的基础上联合靶向治疗（CDK4/6抑制剂、HDAC抑制剂等）1。HER2阳性乳腺癌人群占比为15%-20%。I期5年生存率在94%以上，转移性患者中位OS可达5年4。以曲妥珠单抗为基础的治疗方案是HER2阳性乳腺癌的重要选择：对于符合手术指征的患者可使用为期1年的曲妥珠单抗单药或曲妥珠单抗+帕妥珠单抗的双靶治疗；对于晚期患者一线应首选紫衫类化疗联合曲帕双靶的三联方案（THP方案）1。基于PHILA研究，吡咯替尼+曲妥珠单抗+多西他赛的三联方案（PyHT）也获得了指南推荐5。HER2阳性晚期乳腺癌经曲妥珠单抗治疗病情进展后，仍应持续使用抗HER2靶向治疗。Ⅰ级推荐吡咯替尼+卡培他滨、T-DXd两种方案，Ⅱ级推荐T-DM1。对于HER2 TKI治疗失败的患者，指南推荐使用T-DXd、T-DM1两种HER2 ADC治疗，或继续使用曲帕双靶联合化疗5。TNBC占比约15%，是预后最差的乳腺癌分型。I期5年生存率约为85%，转移性患者中位OS仅10~13个月。由于缺乏作用靶点，TNBC患者通常对内分泌治疗和HER2靶向治疗不敏感，临床治疗方案仍以化疗为主，常用方案包括AC（蒽环类+环磷酰胺）、AC-T（蒽环类+环磷酰胺+紫衫类）、TC（紫衫类+环磷酰胺）等4。TROP2 ADC戈沙妥珠单抗2020年获批用于治疗TNBC，有望改善这一分型的生存结局。近年来，学界仍在持续探索乳腺癌分型的细化，以期实现更精确的患者分层。复旦大学附属肿瘤医院邵志敏教授团队提出的“复旦分型”对患者进行了更精细的划分：TNBC腔面雄激素受体型（LAR）免疫调节型（IM）基底样免疫抑制型（BLIS）间质型（MES）6Luminal型乳腺癌经典腔面型（SNF1）免疫调节型（SNF2）增殖型（SNF3）RTK驱动型（SNF4）7并根据不同亚型的分子特征确定相应分子标志物，有望为乳腺癌新药研发提供新的潜在治疗靶点。02HER2靶向治疗进展目前可选的乳腺癌HER2靶向药物包括曲妥珠单抗、帕妥珠单抗等单抗类药物，吡咯替尼、拉帕替尼等小分子酪氨酸激酶抑制剂（TKI），以及恩美曲妥珠单抗（T-DM1）、德曲妥珠单抗（T-DXd）等ADC。在研HER2靶向药还有RC-48、ARX788等ADC，以及靶向HER2不同位点的双特异性抗体ZW25等。HER2靶向ADC的问世为乳腺癌HER2靶向治疗带来了革命性的改变。针对当前已获批的两种HER2 ADC，DESTINY-Breast 03研究的头对头比较显示，T-DXd相较于T-DM1实现了更大的PFS获益8。因此，2024年的CSCO指南调整了二者的优先级，将T-DXd加入了Ⅰ级推荐；且新版指南将HER2低表达人群从HER2阴性人群中划分出来单列一组，并指出DESTINY-Breast 04研究支持HER2低表达患者也可受益于T-DXd治疗，提示HER2靶向ADC有望进一步拓展适用人群5。03CDK4/6抑制剂进展CDK4/6抑制剂联合内分泌治疗可用于绝经后HR+/HER2-局部晚期和/或转移性乳腺癌，部分药物在围术期治疗中也表现出良好疗效。目前在中国获批的CDK4/6抑制剂有哌柏西利、阿贝西利、瑞波西利3款进口药品和达尔西利1款国产药品。其中，哌柏西利已有13家本土仿制药获得批准。已获批用于肺癌的CDK4/6抑制剂曲拉西利（先声药业）也在积极拓展乳腺癌适应证，但其开展的临床研究系联合戈沙妥珠单抗治疗TNBC，更侧重于发挥骨髓保护作用、减少ADC诱发的骨髓抑制副反应9。嘉和生物在研CDK4/6抑制剂来罗西利的乳腺癌适应证上市申请已获得中国国家药监局（NMPA）受理。目前，学界对于CDK4/6抑制剂治疗的最佳时机存在争议，CDK4/6抑制剂联合治疗方案中的内分泌治疗应如何排序仍缺乏临床证据，CDK4/6抑制剂治疗后进展的患者能否换用其他CDK4/6抑制剂也尚未明确。PACE、postMONARCH等研究正在展开探索，试图解答上述问题，有望指导未来的个体化CDK4/6抑制剂治疗10,11。04其他治疗进展除了HER2靶向治疗和CDK4/6抑制剂治疗，乳腺癌领域还在不断萌生针对其他靶点或采用其他技术的新型疗法。辉瑞和Arvinas合作开发的PROTAC药物ARV-471可特异性降解ER，其在II期VERITAC研究中展现出初步疗效，临床获益率达到38%12。君实生物PD-1特瑞普利单抗联合白蛋白紫杉醇已获得TORCHLIGHT研究的积极数据，向NMPA递交了治疗TNBC的新适应证上市申请13。参考文献：[1] 国家卫健委.《乳腺癌诊疗指南（2022年版）》[2] 中国抗癌协会乳腺癌诊治指南与规范（2024年版）[3] Global surveillance of trends in cancer survival 2000–14 (CONCORD-3)[4] Waks, Adrienne G, and Eric P Winer. Breast Cancer Treatment: A Review. JAMA vol. 321,3 (2019): 288-300.[5] 中国临床肿瘤学会（CSCO）乳腺癌诊疗指南（2024版）[6] Jiang, Yi-Zhou et al. Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies. Cancer cell vol. 35,3 (2019): 428-440.e5.[7] Jin, Xi et al. Molecular classification of hormone receptor-positive HER2-negative breast cancer. Nature genetics vol. 55,10 (2023): 1696-1708.[8] Hurvitz, Sara A et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet (London, England) vol. 401,10371 (2023): 105-117.[9] Trilaciclib combined with sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC): Preliminary phase 2 results. ESMO BC 2023[10] Palbociclib after CDK and endocrine therapy (PACE): A randomized phase II study of fulvestrant, palbociclib, and avelumab for endocrine pre-treated ER+/HER2- metastatic breast cancer. SABCS 2022[11] postMONARCH: A phase 3 study of abemaciclib plus fulvestrant versus placebo plus fulvestrant in patients with HR+, HER2-, metastatic breast cancer following progression on a CDK4 & 6 inhibitor and endocrine therapy. ASCO 2022[12] ARV-471: Phase 2 VERITAC Trial Results. https://ir.arvinas.com/static-files/e0d56eb4-13c4-43e9-935d-f24a18d2fe6e [13] Jiang, Zefei et al. Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial. Nature medicine vol. 30,1 (2024): 249-256.\ | /★联系我们投稿 | 发稿 | 媒体合作▶ sylvia.hua@generalbiologic.com数据库 | 咨询服务 | 资讯追踪▶ 点击左下“阅读原文”完成表单填写点击阅读原文订阅全球行业新闻

CSCO会议抗体药物偶联物临床1期

2024-04-22

·药时代

百亿大关已破！13款FDA批准的ADC，依次交上成绩单

2022年，全球ADC药物销售额突破了70亿美元。2023年，这一数字突破百亿大关，高达102亿美元！据文献预测: 2026 年，ADC 药物的销售额将超 164 亿美元！与化疗药物相比，ADC具有耐受性好、靶标识别准确、对非癌细胞的副作用小等优点，在治疗领域中占据着越来越重要的地位。目前，有13种ADC已被美国食品和药物管理局（FDA）批准，还有超过100种ADC处于不同的临床试验阶段。下面我们就来看看这13款ADC各有什么故事1Gemtuzumab ozogamicin（GO）公司：辉瑞意义：第一个获得全球市场批准的ADC适应症：AML（急性髓性白血病）结构：靶向CD33的人源化单抗+一种细胞毒性N-乙酰-γ-calicheamicin，通过可切割的肼键来连接。作用机制：GO与CD33抗原结合，形成GO-CD33复合物，然后被内吞到AML细胞中。在三个早期临床试验都产生积极结果之后，FDA在2000年批准了GO，特别是用于60岁以上的cd33阳性AML患者的治疗（图二）。图一：GO治疗的细胞作用机理2然而，GO在西南癌症研究集团（SWOG）S0106研究中爆出了安全性问题。该研究旨在评估GO在60岁以下AML成年患者中的疗效。该研究显示，与对照组相比，GO组的细胞致死性诱导率更高（5.5% vs. 1.4%）。与GO治疗相关的作用还包括骨髓抑制、输注反应、感染、出血和肝毒性等等。因此，辉瑞在2010年6月从市场上撤回了该产品。然而，数据表明，与对照组相比，GO对不适合强化化疗的老年AML患者的预后有良好的改善。毒性是可控的。基于这些研究，FDA在2017年又重新批准了GO。后续的研究显示，当GO联合fludarabine、cytarabine、粒细胞集落刺激因子和idarubicin使用时，和单独使用的效果一样，都能减缓疾病进展，尤其在cd33阳性AML患者的初诊中，GO是安全、有效和可行的。2Brentuximab vedotin (BV)公司：Seagen公司，后来与武田公司共同开发，意义：是第二种已获批准的ADC药物。适应症：霍奇金淋巴瘤（HL）和间变性大细胞淋巴瘤（ALCL）结构：布伦妥昔单抗（一种靶向CD30的IgG1嵌合单抗）、马来酰亚胺连接部分（一种可切割的二肽连接，mc-VC-PABC）和单甲基auristatin E（MMAE）。作用机理：BV特异性靶向在中表达的CD30抗原。成绩：2019年，BV在美国和加拿大市场销售额达到6.28亿美元，其他市场销售额达527亿日元，2022年销售额达到14.69亿美元，2023年销售额进一步增加至16.5亿美元。预计2026年BV的全球销售额将达到18亿美元在一项评估BV治疗HL和ALCL的有效性和安全性的I期研究中，大多数副作用事件均为1级和II级，常见的副作用包括疲劳、发烧、腹泻、恶心、中性粒细胞减少等。在一项II期临床试验中，BV分别在75%和87%的HL患者（102例患者）和ALCL患者（30例患者）中显示了有效性。此外，BV还可以缓解淋巴瘤引起的瘙痒和疼痛，而对患者的生活质量没有负面影响。2018年，FDA批准了BV联合CHP（即环磷酰胺、阿霉素和泼尼松）治疗初次用药的系统性ALCL患者或其他表达cd30抗原的成年患者。3Trastuzumab emtansine (T-DM1)公司：Genentech and ImmunoGen结构：通过硫醚连接剂将药物trastuzumab与emtansine（也称为DM1）连接而形成。适应症：HER2阳性癌症患者作用机理：trastuzumab选择性地将高活性的细胞毒性小分子药物DM1转运到HER2过表达的肿瘤细胞中，并通过内吞作用释放药物。这种药用机制不仅显著减少了毒副作用，还增强了靶向作用。成绩：2022年全球销售额为达到21.36亿美元，2023年销售额同比增长4%至22.22亿美元。由于T-DM1仅限于HER2+乳腺癌和仿制药的竞争，销售额2026年将为23亿美元。由Verma等人组织的EMILIA项目证实了T-DM1在HER2阳性晚期乳腺癌患者中的临床作用。在使用T-DM1和紫杉醇治疗的her2阳性晚期或转移的乳腺癌患者中，T-DM1显示出增强的治疗疗效、更高的安全性和更少的不良反应（图三）。轻微的不良反应包括疲劳（49.3%）、恶心（49.3%）、血清天冬氨酸转氨酶升高（43.5%）、发热（40.6%）和头痛（40.6%）。图二：早期公布的研究结果揭示T-DM1组的生存率要优于拉帕替尼联合卡培他滨（9.6比6.4个月）34Inotuzumab ozogamicin (InO)公司：Wyeth Pharmaceuticals Inc结构：通过酸介导不稳定剪接，将靶向CD22的人IgG4单抗与细胞毒性化疗药物calicheamicin偶联而成。适应症：急性淋巴母细胞白血病（ALL）作用机理：InO与表达cd22的肿瘤细胞的结合启动了InO-CD22复合物的内吞作用，导致复合物亚基间连接的水解。随后细胞毒性药物的激活诱导双链DNA断裂，导致细胞周期阻滞和细胞死亡。（CD22抗原是一种135-kDaI的跨膜唾液酸糖蛋白，几乎存在于所有B细胞的细胞质中，并在B细胞上特异性表达。CD22抗原主要表达于同时带有IgM 和IgD的B细胞中。）InO是挽救晚期ALL患者的一种有效措施，它使更多的患者有机会接受干细胞移植，实现长期生存。它最常见的不良反应包括中性粒细胞减少（28%）、AST增加（26%）、恶心（21%）、呕吐（17%）、疲劳（15%）和发热性中性粒细胞减少（15%）。5Moxetumomab pasudotox (MP)公司：阿斯利康意义：20多年来第一个批准用于HCL治疗的药物。结构：靶向CD22的莫西美单抗、假单胞菌外毒素a的38 kDa片段和连接物mc-VC-PABC。适应症：复发/难治性毛细胞白血病（HCL）的成年患者，这些患者对至少两种系统性治疗（包括嘌呤核苷类似物）没有反应。图三：MP开发的重要时间节点4MP最常见的副作用 (3-4级）包括淋巴细胞计数下降（20%）、无症状低磷血症（10%）和贫血（10%）。更新的数据证实，MP在经过大量预处理的HCL患者中表现出较高的持久反应率和最小的疾病残留率。因此它被认为是安全的、可控的治疗方案。6Polatuzumab vedotin (PV)公司：Genetech结构：抗体CD79b通过一个可切割的二肽连接（mc-VC-PABC）与MMAE连接组成适应症：复发/难治的弥漫性大B细胞淋巴瘤（DLBCL）的成人患者作用机理：通过泛素/蛋白酶体系统诱导BCL-2蛋白家族成员MCL-1的降解。成绩：2023年Polivy销售额同比增长108%，至9.46亿美元。预计2026年，PV的全球销售额为8.5亿美元当PV与venetoclax和抗cd20抗体obinutuzumab或利rituximab联合使用时，MCL-1拮抗作用导致非霍奇金淋巴瘤（NHL）消退。重要的是，消退即使在停止治疗后仍然持续，相当比例的患者对治疗反应积极。然而，另一项研究显示，PV联合rituximab和lenalidomide治疗复发/难治性DLBCL患者没有达到预定的治疗效果阈值。最常见的3-4级副反应为中性粒细胞减少症和血小板减少症。7Enfortumab vedotin (EV)公司：安斯泰来和辉瑞结构：通过可切割连接将抗Nectin-4的抗体与细胞毒性药物MMAE结合。适应症：局部晚期或转移性尿路上皮癌（la/ mUC）全局治疗作用机理：EV与Nectin-4结合后，形成一个复合物，会在表达Nectin-4的细胞中被内吞。随后释放的MMAE与细胞微管蛋白结合，破坏微管网络，导致细胞周期阻滞和细胞凋亡。成绩：2022年全球销售额已达7.54亿美元，2023年销售额达到10.3亿美元。预计2026年的全球销售额将达35亿美元I期剂量递增研究EV-101涉及112例接受单药EV治疗的mUC患者。结果显示，研究者评估的有效药物反应率为43%，平均药物反应持续7.4个月。存活率中位数为12.3个月，1年存活率为51.8%。最常见的治疗相关不良事件（TRAEs）的发生率为30%，包括疲劳、脱发、食欲下降、味觉障碍、恶心、周围感觉神经病变、瘙痒和腹泻。FDA批准了EV与pembrolizumab联合治疗（EV+P）为突破治疗（breakthrough therapy）方案，并批准其作为不适合顺铂疗法的la/ mUC患者的一线治疗。8Trastuzumab deruxtecan (T-DXd)公司：Daiichi Sankyo Company, Ltd 结构：Trastuzumab （一种靶向HER2的人源化单抗）与依沙替康（exatecan）衍生物（拓扑异构酶I抑制剂）结合适应症：不可切除或转移性her2阳性乳腺癌患者作用机理：与T-DM1相比，T-DXd可以运载更多的细胞毒性药物。它优越的膜通透性使它能够通过“旁观者效应”杀死更多的肿瘤细胞。成绩：由于T-DXd可用于多种乳腺癌亚群（HER2+、HR+/HER2-和三重阴性）且治疗时间长，预计2026年将以62亿美元成为销量最高的ADC。在一项开放标签、剂量递增和剂量扩大的I期试验中，研究人员评估了T-DXd在表达HER2的晚期实体肿瘤中的安全性、耐受性和药物活性。结果显示，111例患者中有66例证产生了药理反应，111例患者中有104例病情得到控制。所有患者都经历过至少一次不良反应。常见的3级或以上严重的不良反应包括贫血（17%）、中性粒细胞减少（14%）、白细胞减少（9%）和血小板减少（8%）。此外，19%的患者经历了至少一次严重的不良反应，20例患者发生了间质性肺病、组织性肺炎或肺炎。表一：T-DXd各次临床试验的关键数据59Sacituzumab govitecan (SG)公司：Immunomedics意义：全球唯一获批的靶向 Trop-2 ADC 药物结构：包括一个抗trop-2抗体、一个SN-38药物载荷（伊立替康irinotecan的一种活性代谢物）和一个CL2A化学连接适应症：转移性三阴性乳腺癌（TNBC）成人患者作用机理：滋养层细胞表面抗原2（Trop-2）是一种40-kDa的糖蛋白，也被称为肿瘤相关钙信号转换器-2。它在各种实体肿瘤的发展和转移中起着至关重要的作用。SG引人注目的特点包括它对Trop-2的靶向性，以及它运载的中毒性药物SN-38。SG拥有高药物抗体比（7-8：1）。这些都会降低它的脱靶毒性。成绩：上市的首个完整年度业绩为3.8亿美元，2022年全球销售额为6.81亿美元，2023年Trodelvy销售额首次突破十亿美元大关，同比增长56%至 10.63 亿美元。2026销售额预计为11亿美元（表二）表二：SG家族产品销售额临床试验NCT03547973证明了SG治疗在基于铂和ICI治疗失败的局部晚期或转移性尿路上皮癌患者中的临床有效性和安全性。此外，一些研究表明，对EV耐药的细胞对SG仍然敏感，这使得SG可能在大多数膀胱癌亚型中有效，包括那些使用EV治疗的膀胱癌，这标志着尿路上皮癌患者治疗的显著发展。10Belantamab mafodotin (Blenrep)公司：GSK意义：Blenrep是全球获批的第一款BCMA靶向疗法结构：一种靶向B细胞成熟抗原（BCMA）的抗体药物偶联物（ADC），IgG1抗体，通过抗蛋白酶降解的连接子，连接微管抑制剂MMAF组成。适应症：作为一种单药疗法，用于治疗先前已接受过至少4种疗法、且其疾病对至少一种蛋白酶体抑制剂/免疫调节剂/CD38单抗难治、在最后一次治疗中被证明疾病进展的复发或难治性多发性骨髓瘤（R/R MM）成人患者。成绩：Blenrep在 2022 年11 月的验证性 III 期试验中失败，导致 FDA 要求葛兰素史克（GSK）当月将该药物从美国市场撤出。同时相较于其他ADC产品，2021年该产品销量1.22亿美元，2022年1.43亿美元。但在2023年11 月 27 日， Blenrep 二线治疗复发或难治性多发性骨髓瘤（R/R MM）III 期临床 DREAMM-7 试验达到无进展生存期（PFS）的中期主要终点，面临多项BCMA产品的市场竞争，Blenrep的市场前景面临挑战。11Loncastuximab tesirine (LT)公司：ADC Therapeutics结构：包括一个人源化的抗人CD19单抗，通过缬氨酸-丙氨酸连接体连接到吡咯苯二氮卓类（pyrrolobenzodiazepine）二聚体毒素上（图五）。适应症：二线或以上全身治疗的复发/难治性LBCL，包括未指明的DLBCL、低级别淋巴瘤引起的DLBCL和高级别b细胞淋巴瘤。最常见的不良反应包括中性粒细胞减少、血小板减少和伽马-谷氨酰基转移酶升高，39%的患者经历了严重的不良事件，包括中性粒细胞减少、胸腔积液、贫血、心包积液和非心源性胸痛。图四：LT的作用机制图612Tisotumab vedotin (TV)公司：Seagen意义：宫颈癌唯一获批ADC结构：与MMAE结合的完全人源单抗（靶向TF）作用机理：组织因子（TF），又称凝血反应蛋白激酶、凝血因子III或CD142，是一种跨膜糖蛋白。其主要功能是启动外源性凝血途径。TF常在癌细胞表面表达，在肿瘤生长、血管生成和转移中发挥重要作用。TV含有的单抗靶向TF，导致MMAE的内吞和细胞毒性作用。适应症：化疗后有肿瘤生长的成年患者的复发或转移性宫颈癌（r/mCC）在一项I/II期开放标签、剂量递增和扩展研究（innovaTV201；NCT02001623）中，在TF表达的转移性实体肿瘤中评估了TV的安全性、耐受性、药代动力学和抗肿瘤活性。最常见的不良反应是脱发、鼻出血、恶心、结膜炎、疲劳和干眼症。13Mirvetuximab soravtansin (MIRV)公司：ImmunoGen结构：使用FRα靶向抗体，通过一种可裂解的连接物与微管抑制剂相连适应症：治疗FRα表达阳性、铂耐药上皮性卵巢、输卵管或原发性腹膜癌的成年患者，这些患者之前接受过1-3种全身治疗方案作用机理：叶酸受体α（FRα）对叶酸具有较高的亲和力，促进其通过内吞作用运输到细胞质。虽然FRα在正常组织中通常以低水平表达，但它在各种上皮性肿瘤中经常异常表达，包括上皮性卵巢癌、子宫内膜腺癌、TNBC和NSCLC。MIRV含有的单抗靶向FRα。目前，正在进行的研究主要集中在MIRV与其他药物联合治疗卵巢癌患者的安全性和有效性。包括MIRV联合卡铂治疗复发、铂敏感的上皮性卵巢或输卵管癌患者的安全性和抗肿瘤活性。MIRV最常见的不良反应包括腹泻、视力模糊、恶心和疲劳、参考文献：1. Liu K, Li M, Li Y, Li Y, Chen Z, Tang Y, Yang M, Deng G, Liu H. A review of the clinical efficacy of FDA-approved antibody‒drug conjugates in human cancers. Mol Cancer. 2024 Mar 23;23(1):62. doi: 10.1186/s12943-024-01963-7. PMID: 38519953;2. Fenwarth, L.; Fournier, E.; Cheok, M.; Boyer, T.; Gonzales, F.; Castaigne, S.; Boissel, N.; Lambert, J.; Dombret, H.; Preudhomme, C.; et al. Biomarkers of Gemtuzumab Ozogamicin Response for Acute Myeloid Leukemia Treatment. Int. J. Mol. Sci. 2020, 21, 5626.3. Harbeck N, Gluz O, Christgen M, et al. De-escalation strategies in human epidermal growth factor receptor 2 (HER2)–positive early breast cancer (BC): final analysis of the west german study group adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early BC HER2- and hormone receptor–positive phase II randomized trial—efficacy, safety, and predictive markers for 12 weeks of neoadjuvant trastuzumab emtansine with or without endocrine therapy (ET) versus trastuzumab plus ET. J Clin Oncol. 2017 Jul 6. doi: 10.1200/JCO.2016.71.98154. Dhillon S. Moxetumomab Pasudotox: First Global Approval. Drugs. 2018 Nov;78(16):1763-1767. doi: 10.1007/s40265-018-1000-9. Erratum in: Drugs. 2019 Jan;79(1):105. PMID: 30357593;5. Indini A,Rijavec E, Grossi F. Trastuzumab Deruxtecan: Changing the Destiny of HER2Expressing Solid Tumors. Int J Mol Sci. 2021 Apr 30;22(9):4774. doi:10.3390/ijms22094774. PMID: 33946310; PMCID: PMC8125530.6. TsuchikamaK, An Z. Antibody-drug conjugates: recent advances in conjugation and linker chemistries.Protein Cell. 2018 Jan;9(1):33-46. doi: 10.1007/s13238-016-0323-0. Epub 2016Oct 14. PMID: 27743348; PMCID: PMC5777969.封面图来源：pixabay版权声明/免责声明本文为授权转载文章。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cn拜耳Co.Lab上海正式启动招募入驻企业谁说CAR-T不赚钱？为什么医生不愿意开仿制药？点击阅读原文，了解更多！

抗体药物偶联物上市批准申请上市临床结果

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研发状态

适应症	最高研发状态	国家/地区	公司
HER2阳性乳腺癌	批准上市	加拿大更多	Novartis AG 更多
转移性乳腺癌	批准上市	美国更多	Novartis Pharmaceuticals Corp. 更多
早期乳腺癌	临床3期	英国更多	Novartis AG 更多
HER2阳性转移性乳腺癌	终止	-	Novartis Pharmaceuticals Corp. 更多
晚期乳腺癌	终止	中国香港更多	Novartis Pharmaceuticals Corp. 更多

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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


NCT01619111 (DETECT III, Literature) 人工标引	临床3期	HER2 阴性乳腺癌 \| 循环肿瘤细胞 HER2 Positive \| HER2 Negative	101	Standard therapy	膚鑰鬱衊鹹糧願糧築蓋(艱夢觸遞鏇襯廠鏇壓餘) = 夢艱積醖糧獵選構淵鏇範鑰鹽鏇襯壓艱製鹹壓 (糧醖憲範鑰網鹽衊鬱襯 )	积极	2024-01-04
				Standard therapy + Lapatinib	膚鑰鬱衊鹹糧願糧築蓋(艱夢觸遞鏇襯廠鏇壓餘) = 艱艱鑰構網遞衊鏇鏇鑰範鑰鹽鏇襯壓艱製鹹壓 (糧醖憲範鑰網鹽衊鬱襯 )
NCT01619111 (DETECT III, Pubmed)	临床3期	转移性乳腺癌 \| 循环肿瘤细胞	2,137	Lapatinib	鹽選廠醖餘觸鑰繭鏇壓(鬱積範繭簾築廠網糧鬱) = 鹽淵壓鑰衊鑰憲蓋衊獵獵鏇糧鑰網獵衊廠淵網 (醖鬱網鹹繭積艱選範鑰 )	积极	2024-01-04
				Standard therapy	鹽選廠醖餘觸鑰繭鏇壓(鬱積範繭簾築廠網糧鬱) = 鏇齋鹹製鹽膚顧齋範襯獵鏇糧鑰網獵衊廠淵網 (醖鬱網鹹繭積艱選範鑰 )
SABCS2023	N/A	HER2阳性乳腺癌 FGFR4+ \| FGF19	-	Lapatinib	蓋顧鏇鹹襯鏇蓋製繭蓋(觸襯廠範繭襯選鹽窪網) = 糧選艱選廠艱選窪構衊廠膚鹹壓遞製構壓衊廠 (鬱襯鬱憲網獵觸鹽構製, ± 2.1)	-	2023-12-05
				BLU554	蓋顧鏇鹹襯鏇蓋製繭蓋(觸襯廠範繭襯選鹽窪網) = 醖願鏇選鑰衊鏇蓋築廠廠膚鹹壓遞製構壓衊廠 (鬱襯鬱憲網獵觸鹽構製, ± 3.3)
ESMO2023 人工标引	N/A	HER2阳性转移性乳腺癌 HER2 positive	53	lapatinib or pyrotinib	窪衊壓鑰壓鏇糧憲艱餘(繭膚製夢獵窪鹽繭積艱) = 糧觸鹽簾築膚獵築簾鬱膚築鹹鏇選夢淵鏇鑰觸 (蓋衊顧簾網網鏇鑰廠鹽, 7.9 ~ 15.9) 更多	积极	2023-10-21
				lapatinib or pyrotinib (brain metastasis)	窪衊壓鑰壓鏇糧憲艱餘(繭膚製夢獵窪鹽繭積艱) = 淵築衊積鏇範繭淵築艱膚築鹹鏇選夢淵鏇鑰觸 (蓋衊顧簾網網鏇鑰廠鹽, 7.5 ~ 13.5) 更多
NCT01873833 (CTgov)	临床2期	HER2阳性转移性乳腺癌 \| 复发性乳腺癌 \| 转移性乳腺癌 ... 更多	10	laboratory biomarker analysis+Trastuzumab+CYCLOPHOSPHAMIDE+lapatinib ditosylate+capecitabine	艱構鬱窪鑰壓淵淵網願(鬱鑰壓鑰繭壓廠衊齋獵) = 網衊鑰憲鹽簾鏇觸蓋製夢簾選觸蓋觸夢鑰構糧 (選廠艱壓網鹹餘窪齋鑰, 夢憲窪願顧製鬱範齋網 ~ 壓壓製鬱繭廠顧壓餘餘) 更多	-	2023-10-05
NCT01306045 (CTgov)	临床2期	晚期非小细胞肺癌 \| 家族性胸腺瘤 \| 小细胞肺癌 ... 更多	647	Selumetinib (AZD6244)+Erlotinib+Lapatinib+MK-2206+Sunitinib (Non-Small Cell Lung Cancer (NSCLC))	製積獵積膚築蓋積淵醖(遞艱獵蓋糧艱夢選網選) = 醖願淵簾繭齋網願網膚蓋膚構襯蓋窪顧壓遞齋 (鹽蓋醖壓齋構憲觸窪糧, 鬱顧願餘憲廠願艱夢願 ~ 網獵壓蓋鹹蓋衊襯壓膚) 更多	-	2023-04-11
				Selumetinib (AZD6244)+Erlotinib+Lapatinib+MK-2206+Sunitinib (Small Cell Lung Cancer (SCLC))	製積獵積膚築蓋積淵醖(遞艱獵蓋糧艱夢選網選) = 構選餘衊網衊鬱築鹹窪蓋膚構襯蓋窪顧壓遞齋 (鹽蓋醖壓齋構憲觸窪糧, 願醖夢膚齋淵壓鹽鬱壓 ~ 廠壓醖選選鏇醖廠選襯) 更多
ESMO_ASIA2022	N/A	HER2阳性转移性乳腺癌	47	Low dose or metronomic lapatinib (500mg daily with meal)	觸築艱壓夢遞願窪願鹹(蓋積顧壓壓獵網窪憲糧) = 窪鹽餘廠積壓繭顧憲獵鹹糧範襯構艱觸糧鏇鏇 (網壓醖憲鏇繭鑰廠醖餘 ) 更多	-	2022-12-03
Pubmed 人工标引	N/A	HER2阳性胃癌三线 HER2-Positive	59	Lapatinib Ditosylate Hydrate	餘製膚範憲鹽糧選築築(選願鹽顧廠鹹餘艱積壓) = 衊襯憲簾衊衊鏇壓簾積選夢鑰範遞獵繭窪蓋構 (醖製壓製醖繭餘襯遞選 ) 更多	积极	2022-10-01
NCT01273610 (CTgov)	临床2期	HER2阳性转移性乳腺癌 \| HER2阳性乳腺癌	40	pharmacological study+Trastuzumab+Lapatinib	醖願齋醖醖艱鹹蓋廠簾(艱網築夢蓋餘襯膚淵襯) = 壓襯窪襯鬱積網觸製遞膚壓夢夢衊夢願壓鏇夢 (窪鹹廠觸繭觸範範製壓, 壓鹹鏇艱鹹願憲積糧範 ~ 鏇簾觸壓鬱願繭鏇選淵) 更多	-	2022-07-28
ASCO2022	N/A	HER2阳性转移性乳腺癌	102	Lapatinib and capecitabine combination	繭範艱艱蓋淵醖衊齋製(憲窪淵範鹽夢糧範簾鬱) = 壓製壓繭廠醖衊艱築鏇簾衊糧構衊構鹹膚膚積 (觸顧顧鏇鏇襯壓衊窪窪, 5.1 ~ 10.8)	-	2022-06-02