A Randomized, Open-Label, Multicenter, Phase III Study to Evaluate MRG003 vs Cetuximab/Methotrexate as Second/Third Line of Treatment in Patient With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (RM-SCCHN)

The objective of this study is to compare the efficacy and safety of MRG003 versus cetuximab/methotrexate as second/third line of therapy in patients with RM-SCCHN who have previously failed PD-1 (L1) inhibitors and platinum-based therapy.

开始日期2023-03-01

申办/合作机构

上海美雅珂生物技术有限责任公司

NCT05688605 / Recruiting临床1/2期

An Open-label, Multi-center, Phase I/II Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of MRG003 in Combination With HX008 in Patients With EGFR-positive Advanced Solid Tumors

The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG003 in combination with HX008 in patients with EGFR-positive advanced or metastatic solid tumors.

开始日期2022-06-30

申办/合作机构

上海美雅珂生物技术有限责任公司

100 项与 MRG-003 相关的临床结果

登录后查看更多信息

100 项与 MRG-003 相关的转化医学

登录后查看更多信息

100 项与 MRG-003 相关的专利（医药）

登录后查看更多信息

项与 MRG-003 相关的文献（医药）

2022-07-01·JAMA oncology1区 · 医学

Evaluation of Safety of Treatment With Anti–Epidermal Growth Factor Receptor Antibody Drug Conjugate MRG003 in Patients With Advanced Solid Tumors

1区 · 医学

Article

作者: Guo, Ye ; Zhang, Yang ; Liao, Wangjun ; Nian, Weiqi ; Li, Hu ; Wu, Yunteng ; Wei, Xiaoli ; Hu, Chaohong ; Xu, Rui-Hua ; Xu, Zhongyuan ; Qiu, Miao-Zhen ; Zhang, Wenxue ; Xue, Liqiong ; Ren, Guoxin ; Tang, Wenbo ; Jin, Yongshuai ; Wang, Ling ; Guo, Wei ; Xi, Jingle ; Zhao, Hong-Yun

Importance:

The antibody drug conjugate drug MRG003 comprises an anti-epidermal growth factor receptor (EGFR) humanized immunoglobulin G1 monoclonal antibody that is conjugated with monomethyl auristatin E via a valine-citrulline linker. There is currently insufficient evidence of this drug's safety and efficacy.

Objective:

To evaluate the safety and maximum tolerated dose of MRG003 in a phase 1a study and investigate the preliminary antitumor activity in EGFR-expressing patients in a phase 1b study.

Design, Setting, and Participants:

This nonrandomized open-label, single-arm, phase 1, multicenter study of solid tumors was divided into 2 parts, phase 1a dose escalation and phase 1b dose expansion. Patients with advanced or metastatic solid tumors who had failed outcomes from or were not able to receive standard treatment were enrolled in phase 1a without EGFR prescreening. Phase 1b recruited EGFR-positive patients with refractory advanced squamous cell carcinomas of the head and neck (SCCHN), nasopharyngeal carcinoma (NPC), and colorectal cancer (CRC). This study was conducted at 7 Chinese centers between April 11, 2018, and March 29, 2021 (data cutoff date). Data analysis took place between April 2021 and June 2021.

Interventions:

An intravenous dose of 0.1 to 2.5 mg/kg of MRG003 was administered every 3 weeks during phase 1a. During phase 1b, patients were administered the recommended dose identified in phase 1a.

Main Outcomes and Measures:

The primary end points were dose-limiting toxic effects in phase 1a and objective response rate in phase 1b. The safety, tolerability, immunogenicity, and pharmacokinetics of MRG003 were assessed. Tumor assessment was evaluated by RECIST 1.1.

Results:

Twenty-two patients (mean [range] age, 54.5 [32.0-67.0] years; 9 women [41%]) were enrolled in phase 1a and 39 patients (mean [range] age, 50.4 [27.0-75.0] years; 8 women [21%]) in phase 1b. The recommended dose was identified as 2.5 mg/kg. Eighty-nine percent of adverse events (AEs) were associated with MRG003 treatment, and most AEs were grade 1 to 2. Nineteen patients (31%) reported grade 3 or greater treatment-related AEs, including hyponatremia, leukocytopenia, neutropenia, increased aspartate aminotransferase levels, and febrile neutropenia. In phase 1a, 1 patient (5%) achieved a partial response, and 5 (23%) achieved stable disease. In phase 1b, 8 patients (21%) achieved a confirmed partial response, and 12 (31%) achieved stable disease. The objective response rates for SCCHN, NPC, and CRC were 40%, 44%, and 0%, and the disease control rates were 100%, 89%, and 25%, respectively.

Conclusions and Relevance:

The findings of this nonrandomized clinical trial suggest that MRG003 showed a manageable safety profile and promising antitumor activity in patients with EGFR-positive NPC and SCCHN.

Trial Registration:

Clinicaltrials.gov Identifier: NCT04868344.

Frontiers in molecular biosciences3区 · 生物学

Antibody-Drug Conjugates Targeting the Human Epidermal Growth Factor Receptor Family in Cancers

3区 · 生物学

ReviewOA

作者: Yu, Jinfeng ; Fang, Tong ; Yun, Chengyu ; Cai, Xiaoqing ; Liu, Xue

Members of the human epidermal growth factor receptor (HER) family, which includes HER1 (also known as EGFR), HER2, HER3 and HER4, have played a central role in regulating cell proliferation, survival, differentiation and migration. The overexpression of the HER family has been recognized as one of the most common cellular dysregulation associated with a wide variety of tumor types. Antibody-drug conjugates (ADCs) represent a new and promising class of anticancer therapeutics that combine the cancer specificity of antibodies with cytotoxicity of chemotherapeutic drugs. Two HER2-directed ADCs, trastuzumane-emtansine (T-DM1) and trastuzumab-deruxtecan (DS-8201a), have been approved for HER2-positive metastatic breast cancer by the U.S. Food and Drug Administration (FDA) in 2013 and 2019, respectively. A third HER2-directed ADC, disitamab vedotin (RC48), has been approved for locally advanced or metastatic gastric or gastroesophageal junction cancer by the NMPA (National Medical Products Administration) of China in 2021. A total of 11 ADCs that target HER family receptors (EGFR, HER2 or HER3) are currently under clinical trials. In this review article, we summarize the three approved ADCs (T-DM1, DS-8201a and RC48), together with the investigational EGFR-directed ADCs (ABT-414, MRG003 and M1231), HER2-directed ADCs (SYD985, ARX-788, A166, MRG002, ALT-P7, GQ1001 and SBT6050) and HER3-directed ADC (U3-1402). Lastly, we discuss the major challenges associated with the development of ADCs, and highlight the possible future directions to tackle these challenges.

Materials

Effect of Magnetorheological Grease’s Viscosity to the Torque Performance in Magnetorheological Brake

Article

作者: Nazmi, Nurhazimah ; Mohd Yusuf, Shahir ; Mazlan, Saiful Amri ; Abdul Kadir, Khairul Anwar ; Mohamad, Norzilawati ; Adiputra, Dimas ; Shabdin, Muhammad Kashfi ; Nordin, Nur Azmah ; Ubaidillah

Recently, magnetorheological grease (MRG) has been utilized in magnetorheological (MR) brakes to generate a braking torque based on the current applied. However, the high initial viscosity of MRG has increased the off-state torque that led to the viscous drag of the brake. Therefore, in this study, the off-state viscosity of MRG can be reduced by the introduction of dilution oil as an additive. Three samples consist of pure MRG (MRG 1) and MRG with different types of dilution oil; hydraulic (MRG 2) and kerosene (MRG 3) were prepared by mixing grease and spherical carbonyl iron particles (CIP) using a mechanical stirrer. The rheological properties in the rotational mode were examined using a rheometer and the torque performances in MR brake were evaluated by changing the current of 0 A, 0.4 A, 0.8 A, and 1.2 A with fixed angular speed. The result shows that MRG 3 has the lowest viscosity which is almost 93% reduction while the viscosity of MRG 2 has lowered to 25%. However, the torque performances generated by MRG 3 were highest, 1.44 Nm, when 1.2 A of current was applied and followed by MRG 2 and MRG 1. This phenomenon indicated that the improvement of torque performances was dependent on the viscosity of MRG. By reducing the viscosity of MRG, the restriction on CIP to form chain formation has also decreased and strengthen the torque of MRG brake. Consequently, the utilization of dilution oil in MRG could be considered in MR brake in near future.

项与 MRG-003 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

2024-04-07

·药智网

“小而美”Biotech迎来曙光

春暖花开的季节，也是各家年报密集披露的时期，有人欢喜有人愁。其中，有这样一家Biotech企业，收入同比增加1347.2%，年内亏损大幅减少96.8%，盈利在望。这就是乐普生物。作为一家“小而美”的ADC Biotech，乐普生物如何突出重围？01“小而精”研发路线不同于某些Biotech追求“大而全”（囊括各种药物类型、堆砌管线），乐普生物主要走“小而精”研发路线，即聚焦于具有差异化竞争优势的ADC药物研发。众所周知，当前ADC药物主要扎堆热门靶点HER2，后来者想在激烈的市场竞争中占得一席之地，难度非常大。而选择布局差异化靶点，或避开热门癌种，是明智的策略。基于此，乐普生物布局了具备差异化优势的ADC管线，包括MRG003（EGFR靶向ADC）、MRG002（HER2靶向ADC）、MRG004A（TF靶向ADC）、MRG001（CD20靶向ADC）、CMG901（CLDNI8.2靶向ADC），其中有些ADC具备BIC或FIC潜力。乐普生物研发管线图片来源：乐普生物2023年财报例如，MRG003是国内首创的EGFR ADC，适应症主要针对二线及以上NPC（鼻咽癌）、HNSCC（头颈部鳞状细胞癌），目前均已开展III期试验，进度处于全球前三、国内第一，今年还有望申报鼻咽癌适应症上市。鼻咽癌虽不是大癌种，却存在巨大的临床未满足需求，单药化疗或PD-1/PD-L1抑制剂二线及以上治疗复发转移性鼻咽癌的ORR仅20%-30%，疗效有限。相较之下，MRG003在鼻咽癌IIa期研究中展现了亮眼数据：针对经PD-1/PD-L1及含铂化疗治疗的NPC患者，ORR为47.4%。2.0mg/kg剂量组的ORR为39.2%，mPFS为7.3个月；2.3mg/kg剂量组的ORR为55.2%。基于良好的数据，FDA授予MRG003治疗鼻咽癌的孤儿药认定、快速通道资格。临近商业化的ADC药物，还有靶向HER2的MRG002。目前，MRG002正在中国进行HER2高表达乳腺癌肝转移II期关键临床试验，并已观察到良好数据，正在做报产准备。同时，正在开展针对HER2阳性乳腺癌、尿路上皮癌患者的III期临床试验。乐普生物的“小而精”研发路线，不仅反映在适应症的选择，还体现在PD-1+ADC联合疗法的研发上。据华创证券研报披露，现有的IO疗法中，近一半方案可能从IO+化疗升级为IO+ADC，相关适应症市场有望实现100-200%扩容。如今，IO+ADC联合疗法已是兵家必争之地。图片来源：华创证券研报目前，乐普生物“普特利单抗+MRG003”已在鼻咽癌及头颈部鳞状细胞癌II期试验中观察到良好的数据，“普特利单抗+MRG002”正在进行治疗HER2表达实体瘤患者的II期试验，并在尿路上皮癌患者中观察到良好的初步数据。除MRG003外，MRG004A同样瞄准未满足的临床需求，且是国内首个申报临床的TF ADC，目前正在中美两国开展治疗复发性或难治性胰腺癌的Ⅰ期临床试验，并已在TNBC（三阴乳腺癌）、CC（宫颈癌）中观察到良好数据。由于胰腺癌起病隐匿、诊断困难，且治疗手段有限、致死率高（患者总生存期仅6-9个月），被医学界称为“癌中之王”。无论PD-1/PD-L1单抗还是ADC“药王”DS-8201，都对胰腺癌束手无策。如果之后MRG004A能拿下胰腺癌，势必成为“香饽饽”。从市场角度看，全球仅有一款TF ADC药物获批上市，来自Seagen的Tivdak，已获批宫颈癌、卵巢癌适应症，再鼎医药拥有中国权益。02减少亏损的秘密随着国内创新药行业遭遇资本“寒冬”，Biotech们使出浑身解数优化现金流管理。乐普生物也不例外，通过综合性收入在2023年度实现亏损大幅收窄，主要得益于商业化收入大幅增加及公司投资活动确认的其他利得增加。其中，PD-1单抗普特利单抗实现销售收入1.01亿元，同比大幅增加551%，与康诺亚合作研发的CLDNI8.2 ADC药物CMG901获得BD及技术服务收入1.24亿元，通过出售皓阳生物15%股权获得收益1.04亿元，持有的武汉滨会因股权摊簿录得收益1.16亿元。乐普生物2023年业绩表现图片来源：乐普生物2023年财报此外，乐普生物还积极采取降本增效措施，提升整体盈利能力。其中，2023年研发开支较2022年5.24亿元减少12.6%，行政开支较2022年1.39亿元减少0.34亿元。面对创新药资本寒冬，Biotech不仅要“节流”，更要“开源”。通过持续进行研发活动，乐普生物已将多款核心管线推至后期研发阶段，同时提前布局ADC联合PD-1适应症市场，实现PD-1销售收入稳步增长，并积极推进海外BD、受托提供CDMO服务。这一时期通常需要大量的资金投入来支持临床试验、生产准备和市场推广等活动。截至2023年，乐普生物现金及现金等价物为4.26亿元，较2022年6.69亿元减少了2.43亿元。不过，在海外BD方面，乐普生物有着明确的战略规划，已储备多款BD资源。这也是未来几年能否实现扭亏为盈的重要看点。03如何冲击盈利？在亏损显著减少后，实现盈利成为乐普生物接下来的目标。这也是所有Biotech的目标。2023年度，有不少Biotech实现扭亏为盈，包括和铂医药、康方生物、和黄医药、复宏汉霖。业绩扭亏的原因，都与对外授权交易有关。实际上，通过对外授权获得现金流、做起CXO（医药外包服务）生意，正是乐普生物实现扭亏为盈的战略要点。2023年，乐普生物将与康诺亚合作研发的潜在首创Claudin 18.2 ADC药物CMG901的全球权益授予跨国制药巨头阿斯利康。目前，乐普生物和康诺亚已获得6300万美元的预付款，未来还将获得高达11亿美元的潜在里程碑付款及高达低双位数的分层特许权使用费。另外，乐普生物还受托提供CDMO服务。去年11月，乐普生物与乐普医疗有条件订立GLP-1等相关产品CDMO服务框架协议，将向乐普医疗及/或其附属公司提供的CDMO服务涵盖CMC技术服务。正如乐普生物在公告中所言，之所以订立CDMO服务框架协议，是考虑到“在适当的机会出现时通过提供CDMO服务更有效利用富余产能，可为公司整体产生补充现金流量”。除CMG901外，乐普生物MRG003、MRG004A都存在BD的机会。MRG003是进度处全球前三的EGFR ADC，正在冲刺商业化，上市后有望享受到市场独占的红利，而且在鼻咽癌、头颈部鳞状细胞癌研究中已观察到令人鼓舞的数据。事实上，基于大药潜质，EGFR靶向药物已成为巨头必争之地，例如EGFR-TKIs类药物“王者”奥希替尼2023年销售额近58亿美元、强生EGFR/c-Met双抗埃万妥单抗剑指50亿美元、百利天恒EGFR/HER3双抗ADC药物BL-B01D1达成最高84亿美元授权交易。MRG004A同样具备大药潜质，全球首款且目前唯一获批的TF ADC产品Tivdak，已验证TF靶点的成药性，机构预测其销售峰值有望超过12亿美元。相较Tivdak，MRG004A已初步显示出一定优势，包括半衰期更长、有效性可能更好，毒性可能更低，安全性较好。为了实现盈利，乐普生物不仅破拆BD的砖墙，还前瞻性布局了溶瘤病毒管线。CG0070便是乐普生物从CG Oncology公司引进的潜在FIC溶瘤病毒疗法，后者已推至临床Ⅲ期阶段，并已展现出比现有获批疗法更优的疗效数据和安全性。目前，乐普生物正在中国开展CG0070的I期临床试验，后续有望开展桥接试验，快速实现上市。更值一提的是，CG0070联合PD-1单抗“全球药王”K药已初步显示出较单药更优异的数据。乐普生物也开展了自身核心产品普特利单抗联用CG0070治疗高危BCG无反应非肌层浸润性膀胱癌的I/II临床。04结语作为一家“小而美”的ADC Biotech，乐普生物选择走“小而精”的研发路线，管线布局可谓一环套一环：以PD-1单抗为基石，顺势开展多项“PD-1单抗+ADC”、“PD-1单抗+溶瘤病毒”联合疗法临床试验。另外，为了能持续开展研发活动、冲击盈利，乐普生物还通过各种渠道或途径获得收入，“精细调配现金流”的策略展露无疑。在创新药投融资遇冷的当下，乐普生物的战略规划无疑起到很好的示范作用。但这也只是起点，在研管线能否实现商业化、何时实现盈利，还有待继续观察。参考资料：1.乐普生物财报、公告、官网2.《大幅缩亏，ADC龙头腾飞在即》，瞪羚社，2024-03-293.华创证券研报声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 金银花转载开白 | 马老师 18996384680（同微信）商务合作 | 王存星 19922864877（同微信）阅读原文，是昨天最受欢迎的文章哦

抗体药物偶联物财报快速通道孤儿药临床3期

2024-04-03

·CPHI制药在线

亏损收窄、产品销售获突破，乐普生物交出亮眼成绩单

关注并星标CPHI制药在线近日，中国ADC Biotech乐普生物披露2023年业绩报告：全年实现收入2.25亿元，同比大幅增长1347.2%；年度亏损0.22亿元，相比2022年亏损6.89亿元的幅度大幅减少（缩减幅度96.8%），经调整年内净亏损减少至2.5亿元。目前虽未实现盈利，但公司的核心管线正在逐步落地商业化，另外乐普生物还有CDMO技术服务等多渠道收入，公司的商业化能力正在得到验证。销售+BD，维持现金流稳定性乐普生物第一个实现商业化的产品是PD-1抑制剂普特利单抗（商品名：普佑恒），该产品于2022年7月首次在国内获批上市，用于既往接受一线及以上系统治疗失败的高度微卫星不稳定型（MSI-H）或错配修复缺陷型（dMMR）晚期实体瘤患者的治疗。2022年9月底，普特利单抗的新适应症获NMPA附条件批准上市，用于既往接受全身系统治疗失败的不可切除或转移性黑色素瘤患者的治疗。普特利单抗为人源化IgG4单抗，在IgG4的Fc区引入了三重突变（S254T/V308P/N434A突变）以延长半衰期。I 期临床中，单次给药半衰期为17-24天，稳定后半衰期为18-38天。因此尽管该产品是国内获批的第10 款PD-1单抗，但基于独特的结构以及差异化的适应症布局，普特利单抗2023年销售额突破1亿元（1.01亿元）。除了上市产品销售为公司带来现金流外，乐普生物也在通过BD授权渠道补充现金流。2023年2月，乐普生物与阿斯利康达成关于CMG901的独家授权合作，CMG901是乐普生物旗下一款靶向Claudin18.2的ADC药物，由抗Claudin18.2单克隆抗体、可裂解的链接体和细胞毒性小分子单甲基澳瑞他汀E（MMAE）组成。根据协议，阿斯利康将负责CMG901的全球研发、制造和商业化，乐普生物将获得6300万美元的预付款和超过11亿美元的潜在额外研发和销售相关的里程碑付款。目前，该BD授权许可收入已到账1.09亿元，成为乐普生物商业化另一大收入来源。通过销售+BD方式，乐普生物获得了稳定的现金流，以进行其他产品研发。多款产品即将迎来收获期在管线布局上，乐普生物重点布局了ADC、肿瘤免疫疗法及溶瘤病毒三大板块。乐普生物的ADC管线进展在国内处于第一梯队，其ADC候选药物包括MRG003、MRG002、MRG004A及MRG001。 MRG003是一款EGFR-ADC，由EGFR靶向单克隆抗体与强效的微管抑制有效载荷一甲基澳瑞他汀E分子通过缬氨酸-瓜氨酸链接体偶联而成的ADC。能够特异性地结合肿瘤细胞表面的EGFR，通过内吞及溶酶体蛋白酶裂解后释放强效的有效载荷，从而导致肿瘤细胞死亡。 2023年12月，MRG003已获FDA授予快速通道资格，用于治疗复发或转移性鼻咽癌（R/M NPC）。同时，MRG003与PD-1联用的I期临床研究正在探索中。 MRG002是一款创新性HER2靶向ADC，由糖型优化的曲妥珠单抗通过可酶切vc连接子与MMAE偶联而成。与曲妥珠单抗相比，由于其抗体成分可促进岩藻糖基化，从而降低抗体Fc区的ADCC活性，提高了安全性。MRG002用于治疗胃癌及胃食管结合部腺癌已获FDA授予孤儿药资格。 MRG004A是一款TF靶向ADC产品，已分别在美、中取得IND批准，目前正在美国及中国进行I/II期临床研究，并已在胰腺癌、三阴乳腺癌及宫颈癌等适应症中观察到抗肿瘤活性信号。由于MRG004A具备更长的半衰期、更好的耐受性，对应更宽的治疗窗，因此有望成为TF靶向ADC赛道的BIC。 MRG001是一款靶向CD20的ADC产品，由重组嵌合抗CD20单抗与MMAE偶联而成。目前正在进行II期临床研究，用于经至少2线治疗失败的复发/弥漫性大B细胞瘤（R/R DLBCL）患者。在溶瘤病毒领域，乐普生物于2021年引进了美国CG Oncology公司的溶瘤病毒药物CG0070，这是一种基因修饰的5型腺病毒（Ad5），被修饰后包含癌症选择性启动子E2F-1和免疫细胞刺激因子GM-CSF基因，选择性地在Rb调控缺陷的肿瘤细胞内复制并裂解肿瘤细胞。目前CG0070在做与其他药物（比如Keytruda）联用的探索，以求进一步扩大潜在的适应症范围和寻求效用更高的治疗方式。除此之外，乐普生物还受托为乐普医疗GLP-1产品提供CDMO生产业务，多渠道的收入来源将为公司的平稳运营提供保障。随着多款候选产品进入收获期，乐普生物的未来值得期待。主要参考资料： 1.乐普生物2023业绩报告. 2.https://www.abstractsonline.com/pp8/#!/20272/session/609. 3.乐普生物公告. 【智药研习社近期课程预告】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~

抗体药物偶联物引进/卖出财报上市批准临床1期

100 项与 MRG-003 相关的药物交易

登录后查看更多信息

研发状态

适应症	最高研发状态	国家/地区	公司
转移性头颈部鳞状细胞癌	临床3期	中国更多	上海美雅珂生物技术有限责任公司更多
头颈部复发性皮肤鳞状细胞癌	临床3期	中国更多	上海美雅珂生物技术有限责任公司更多
鼻咽癌	临床3期	-	乐普生物科技股份有限公司更多
HER2阳性实体瘤	临床1期	中国更多	上海美雅珂生物技术有限责任公司更多
晚期恶性实体瘤	无进展	中国更多	上海美雅珂生物技术有限责任公司更多

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04868162 (ESMO2023) 人工标引	临床2期	头颈部鳞状细胞癌 EGFR expression	67	MRG003	遞鬱簾糧憲構鹹艱壓選(齋醖憲構繭積範鹹簾壓) = 願積觸構壓鑰蓋繭遞積簾鬱築範憲鹹繭築艱襯 (範獵鹽鹹顧齋簾選選觸 )	积极	2023-10-22
				MRG003 (2.3 mg/kg)	遞鬱簾糧憲構鹹艱壓選(齋醖憲構繭積範鹹簾壓) = 廠膚窪鹹觸鑰簾選顧築簾鬱築範憲鹹繭築艱襯 (範獵鹽鹹顧齋簾選選觸 ) 更多
NCT05126719 (MRG003, ESMO2023) 人工标引	临床2期	鼻咽癌	61	MRG003	壓繭衊憲築憲淵廠觸鹹(齋選廠糧憲積製鹽鹹範) = 鑰壓鏇網窪齋淵襯窪簾齋範簾範襯齋淵觸選齋 (襯窪淵憲膚繭鹽壓製鹹 ) 更多	积极	2023-10-21
				MRG003	壓繭衊憲築憲淵廠觸鹹(齋選廠糧憲積製鹽鹹範) = 選廠艱鑰遞淵醖獵醖齋齋範簾範襯齋淵觸選齋 (襯窪淵憲膚繭鹽壓製鹹 ) 更多
MRG003 (CSCO2022)	临床2期	复发性鼻咽癌末线	61	MRG003 2.0mg/kg	餘構顧願鬱餘鑰鏇觸網(遞鑰鏇觸鹹選夢鑰鹹艱) = 鬱鏇膚築觸網網窪鏇範糧鏇壓廠衊鑰鹽鬱觸膚 (願襯顧繭醖餘簾願繭衊 ) 更多	积极	2022-09-21
				MRG003 2.3mg/kg	餘構顧願鬱餘鑰鏇觸網(遞鑰鏇觸鹹選夢鑰鹹艱) = 齋艱鹹鬱蓋願窪顧簾淵糧鏇壓廠衊鑰鹽鬱觸膚 (願襯顧繭醖餘簾願繭衊 ) 更多
NCT04868344 (Pubmed \| JAMA Oncol)	临床1期	HR阳性/HER2低表达实体瘤	61	MRG003	夢廠選遞廠顧襯獵觸構(窪構網齋廠艱糧襯製簾) = Eighty-nine percent of adverse events (AEs) were associated with MRG003 treatment, and most AEs were grade 1 to 2. Nineteen patients (31%) reported grade 3 or greater treatment-related AEs, including hyponatremia, leukocytopenia, neutropenia, increased aspartate aminotransferase levels, and febrile neutropenia. 觸觸襯膚壓窪選簾鹹範 (衊夢蓋憲鹽夢願醖積範 )	积极	2022-05-05
CTR20180310 (ESMO2021)	临床1期	HR阳性/HER2低表达实体瘤	22	MRG003 0.1 mg/kg	鹹積簾壓製膚糧蓋膚製(醖選夢範膚餘膚製糧壓) = 30% 觸簾糧夢觸艱衊醖選顧 (鏇範壓繭衊選淵憲範範 ) 更多	-	2021-09-16
				MRG003 2.5 mg/kg
CTR20180310 (ASCO2020)	临床1期	实体瘤	22	MRG003	衊築衊範積壓齋製觸觸(鬱鑰餘鹹蓋壓衊鹹蓋鹹) = 餘鹹艱艱範繭餘艱衊齋鬱衊廠衊餘願製範衊遞 (製積簾製觸鹽鬱範鹽膚 ) 更多	积极	2020-05-25