The goal of this clinical trial is to test in Chinese Subjects with Metastatic or Recurrent Solid Malignancies. The main questions it aims to answer are:
How is the PK of tisotumab vedotin?
How is the immunogenicity of tisotumab vedotin?
How is the safety and tolerability of tisotumab vedotin?
How is the clinical efficacy of tisotumab vedotin? Participants will receive 2.0 mg/kg tisotumab vedotin (up to a maximum of 200 mg in subjects ≥ 100 kg) as a 30-minute IV infusion 1Q3W with the aim to characterize the PK profiles and to evaluate immunogenicity, safety, and tolerability of tisotumab vedotin in the Chinese population.
Subjects will receive study treatment until disease progression or any other discontinuation criteria are met, whichever occurs first. Subjects will undergo an end of treatment (EOT) visit 30 days (± 5 days) after the last dose of study treatment or within 7 days after treatment discontinuation has been decided, whichever occurs later.

开始日期2023-06-16

申办/合作机构

再鼎医药（上海）有限公司

CTR20231348

/ Completed临床1期

一项在复发或转移性的中国实体瘤受试者中评估Tisotumab Vedotin药代动力学的开放性Ⅰ期试验

主要：评估tisotumab vedotin的PK。次要：评估tisotumab vedotin的免疫原性。评估tisotumab vedotin的安全性和耐受性。探索性：评估tisotumab vedotin的临床疗效。

开始日期2023-06-06

申办/合作机构

再鼎医药（上海）有限公司

[+2]

CTR20223290

/ Active, not recruiting临床3期

一项在二线或三线复发性或转移性宫颈癌患者中比较 Tisotumab vedotin 与研究者所选化疗方案的随机、开放标签、III 期试验

主要目的：在 2L-3L 宫颈癌参与者中证明 Tisotumab vedotin 相较于化疗的临床疗效改善次要目的：1.在 2L-3L 宫颈癌参与者中评估 Tisotumab vedotin 相较于化疗的临床疗效改善 2.在 2L-3L 宫颈癌参与者中证明 Tisotumab vedotin 相较于化疗的抗肿瘤活性改善 3.在 2L-3L 宫颈癌参与者中表征 Tisotumab vedotin 和化疗的抗肿瘤应答 4.评估 Tisotumab vedotin 的安全性和耐受性 5.评估健康相关生活质量 (HRQOL) 6.评估 Tisotumab vedotin 的药代动力学 (PK) 和免疫原性

开始日期2023-02-09

申办/合作机构

湃朗瑞医药科技（北京）有限公司

100 项与替索单抗相关的临床结果

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100 项与替索单抗相关的转化医学

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100 项与替索单抗相关的专利（医药）

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651

项与替索单抗相关的文献（医药）

2025-04-01·Gynecologic Oncology Reports

Second-line antibody-drug conjugates for the treatment of metastatic human papillomavirus-independent gastric-type adenocarcinoma of cervix: The Singapore experience

Article

作者: Aggarwal, Ieera Madan ; Li, Yihan ; Chan, Jack Junjie ; Bok, Ke Xin ; Wong, Shing Lih ; Wang, Junjie ; Ang, Daniel Jia Ming ; Yeo, Yen Ching ; Wong, Adele

Human papillomavirus (HPV)-independent gastric-type adenocarcinoma (GAS) is a rare, aggressive, chemoresistant histological subtype of cervical cancer which occurs more commonly in patients of Asian descent. Patients with GAS tend to have poorer overall outcomes compared to HPV-associated adenocarcinomas of the cervix. The antibody-drug conjugates (ADCs) tisotumab vedotin-tftv (TV) and trastuzumab deruxtecan (T-DXd) are approved for use in previously treated metastatic cervical cancer, the latter in HER2-expressing tumors. There is paucity of data regarding the efficacy and safety of TV and T-DXd in the management of metastatic GAS. We report outcomes of four patients with metastatic GAS who were treated with these ADCs in the second-line setting in Singapore.

2025-04-01·GYNECOLOGIC ONCOLOGY

Clinical applications of antibody drug conjugates for gynecologic malignancies: Review of available medicines and emerging therapeutics

Review

作者: Solaru, Samantha A ; Bujnak, Alyssa C ; Tewari, Krishnansu

With significant overall survival benefits reported in several phase 3 randomized clinical trials, the integration of anti-PD-1 immunotherapy with systemic chemotherapy has transformed the therapeutic landscape in advanced endometrial cancer and PD-L1+ recurrent/metastatic cervical cancer. For patients with FIGO stage III-IVA locally advanced cervical cancer, irrespective of PD-L1 status, chemoradiation plus pembrolizumab followed by maintenance pembrolizumab also confers a survival benefit. For newly diagnosed advanced ovarian cancer responding to primary systemic chemotherapy, maintenance therapy using PARP inhibitors and/or bevacizumab according to germline and somatic mutational analysis have been demonstrated to improve progression-free survival. Tumor heterogeneity, acquired drug resistance, and adverse events limit long-term effectiveness. Antibody-drug conjugates (ADCs) represent an innovative new class of medicines with activity in gynecologic malignancies and distinct toxicity profiles attributable to ADC construction. Adverse event mitigation strategies, biomarker discovery, and sequencing are paramount in successfully exploiting the therapeutic window provided by these novel compounds. This review discusses the application of ADCs in gynecologic cancers, including the current FDA-approved drugs mirvetuximab soravtansine, tisotumab vedotin, and trastuzumab deruxtecan, as well as relevant ongoing clinical trials, including TROP2 ADCs.

2025-03-01·ANNALS OF EMERGENCY MEDICINE

Antibody-Drug Conjugates: The Toxicities and Adverse Effects That Emergency Physicians Must Know

Review

作者: Markides, Danna Michelle ; Merlin, Jeffrey ; Hita, Angel Guido ; Reyes-Gibby, Cielto ; Yeung, Sai-Ching J

Antibody-drug conjugates are novel antineoplastic agents whose use is expanding, both in terms of the number of drugs and the number of patients being treated. This article reviews the known toxicities and complications of antibody-drug conjugates that are currently approved for the treatment of cancer in the United States, with a focus on their emergency presentation and management. Similar to many other cancer therapies, most antibody-drug conjugates can cause diarrhea, nausea/vomiting, rash, peripheral neuropathy, and cytopenia, which are generally treated following standard-of-care. Interstitial lung disease, which may mimic pneumonia and cause respiratory failure and death, has been seen with trastuzumab deruxtecan and mirvetuximab soravtansine; emergency treatment of this condition includes oxygenation, ventilatory support, and corticosteroids. Inotuzumab ozogamicin and gemtuzumab ozogamicin are both associated with sinusoidal obstruction syndrome, a potentially fatal liver dysfunction that presents with weight gain, fluid overload, and jaundice. Abnormal liver function tests in patients who have been recently treated with these agents should be cautiously evaluated. Cardiac adverse events with antibody-drug conjugates are rare, but trastuzumab emtansine and trastuzumab deruxtecan may cause a decrease in cardiac contractility, and heart rate corrected QT interval prolongation is a rare effect of trastuzumab deruxtecan. Ocular adverse events, especially blurred vision, and keratopathy, are common with mirvetuximab soravtansine and tisotumab vedotin. Progressive multifocal leukoencephalopathy has been reported with brentuximab vedotin and polatuzumab vedotin. Tumor lysis syndrome may occur after treatment with gemtuzumab ozogamicin, polatuzumab vedotin, and brentuximab vedotin. Patients receiving enfortumab vedotin or brentuximab vedotin may develop hyperglycemia, sometimes presenting as diabetic ketoacidosis. Tisotumab vedotin and trastuzumab emtansine are associated with bleeding; although it is minor in most cases, severe bleeding and intracranial hemorrhage have occurred. Several antibody-drug conjugates can cause an anaphylactoid infusion-related reaction, which occurs most commonly during or soon after infusion but may be delayed up to 24 hours. Further research is needed to establish the real-world incidence of rare complications and how often patients with these complications present to the emergency department.

305

项与替索单抗相关的新闻（医药）

2025-03-31

·PipelineReview

TIVDAK® (tisotumab vedotin) Approved by European Commission for Previously Treated Recurrent or Metastatic Cervical Cancer

COPENHAGEN, Denmark I March 31, 2025 I Genmab A/S (Nasdaq: GMAB)announced today that the European Commission (EC) has granted marketing authorization for TIVDAK ® (tisotumab vedotin), an antibody-drug conjugate (ADC), as monotherapy treatment for adult patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy. TIVDAK is the first and only ADC to be granted European Union (EU) marketing authorization for people living with recurrent or metastatic cervical cancer. Despite progress in cervical cancer prevention and early detection, there remains a high need for new treatment options, particularly in advanced forms of the disease. In fact, cervical cancer is the fourth most common cause of cancer death among women globally. i In the European Union, cervical cancer is the 11 th most frequently occurring cancer among women. ii Up to 15% of adults with cervical cancer present with metastatic disease at diagnosis iii,iv and, for those diagnosed at earlier stages who receive treatment, up to 61% v will experience disease recurrence. For these patients, the prognosis can be poor. vi “Recurrent or metastatic cervical cancer is a devastating disease, and patients can face a difficult treatment journey with limited options,” said Ignace Vergote, M.D., Ph.D., University Hospitals Leuven, co-founder of European Network of Gynaecological Oncological Trial groups (ENGOT), and lead investigator on the innovaTV 301 clinical trial. “In clinical trials, TIVDAK demonstrated a superior overall survival benefit and manageable safety profile compared to chemotherapy, supporting its position to become a potential new standard of care in this setting with a novel mechanism of action. This approval is an important step forward in the treatment landscape for advanced cervical cancer.” The approval is supported by data from the global, randomized, Phase 3 innovaTV 301 trial (NCT04697628) that evaluated the efficacy and safety of TIVDAK compared to chemotherapy in patients with advanced or recurrent cervical cancer who were previously treated with chemotherapy. The trial met its primary endpoint of overall survival (OS), demonstrating a 30% reduction in risk of death (HR: 0.70 [95% CI: 0.54-0.89], two-sided p=0.0038) compared to chemotherapy. Median OS was 11.5 months [95% CI: 9.8-14.9] among patients treated with TIVDAK compared to 9.5 months [95% CI: 7.9-10.7] for patients who received chemotherapy. Secondary endpoints of progression-free survival (PFS) and confirmed objective response rate (ORR) were also met, further validating its clinical benefit. PFS results were statistically significant, with TIVDAK demonstrating a 33% reduction in the risk of disease progression compared with chemotherapy (HR: 0.67 [95% CI, 0.54-0.82], p<0.0001). Data from the innovaTV 204 (NCT03438396) pivotal Phase 2 single-arm clinical trial evaluating TIVDAK as monotherapy in patients with previously treated recurrent or metastatic cervical cancer was also included in the marketing authorization application (MAA). The most common (≥25%) adverse reactions, including laboratory abnormalities, in patients receiving tisotumab vedotin were peripheral neuropathy (39%), nausea (37%), epistaxis (33%), conjunctivitis (32%), alopecia (31%), anaemia (27%), and diarrhoea (25%). “We recognize the urgent need to accelerate science and innovate new treatment options for gynecologic cancers, including cervical cancer,” said Brad Bailey, Executive Vice President and Chief Commercial Officer of Genmab. “The European Commission approval of TIVDAK marks a milestone in our work to transform the treatment paradigm and help improve outcomes for patients. As the first medicine that Genmab will bring to patients in Europe independently, we’re committed to bringing this important option to as many patients in Europe with previously treated recurrent or metastatic cervical cancer as possible.” About the innovaTV 301 Trial The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating tisotumab vedotin versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who received one or two prior systemic regimens in the recurrent or metastatic setting. Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology, and disease progression during or after treatment with chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint was overall survival. The main secondary outcomes were progression-free survival and objective response rate. The study was conducted by Seagen, which was acquired by Pfizer in December 2023, in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057), as well as other global gynecological oncology cooperative groups. For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov . About Tisotumab Vedotin Tisotumab vedotin (approved under the brand name TIVDAK ® in the EU, U.S. and Japan) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity. About the Pfizer and Genmab Collaboration Tisotumab vedotin is co-developed and co-commercialized globally by Genmab and Pfizer, under an agreement in which the companies share costs and profits. With respect to the commercialization of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer, Genmab leads commercialization in Europe and all other regions globally, outside the United States and China. In these regions, Pfizer partners with Genmab and Zai Lab, respectively, on commercialization. Pfizer is currently the marketing authorization holder (MAH) for tisotumab vedotin in the European Union. This responsibility is expected to transfer to Genmab in 2025. TIVDAK ® (tisotumab vedotin-tftv) U.S. Indication and Important Safety Information Indication TIVDAK is a tissue factor-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. About Genmab Genmab is an international biotechnology company with a core purpose of guiding its unstoppable team to strive toward improving the lives of patients with innovative and differentiated antibody therapeutics. For more than 25 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational, quantitative and data sciences, resulting in a proprietary pipeline including bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators and effector function-enhanced antibodies. By 2030, Genmab’s vision is to transform the lives of people with cancer and other serious diseases with knock-your-socks-off (KYSO ® ) antibody medicines. Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit Genmab.com and follow us on LinkedIn and X . i Wu, Jie, and Qianyun Jin. “Global Burden of Cervical Cancer: Current Estimates, Temporal Trend and Future Projections Based on the Globocan 2022.” Journal of the National Cancer Center, 23 Jan. 2025, www.sciencedirect.com/science/article/pii/S2667005425000134 . ii “Cervical Cancer Burden in EU-27 – Europa.Eu.” Cancer Factsheets in EU-27 Countries, ECIS – European Cancer Information System, 17 Nov. 2021, https://ecis.jrc.ec.europa.eu/sites/default/files/2023-12/cervical_cancer_en-Nov_2021.pdf . iii National Cancer Institute. SEER Cancer Stat Facts: Cervical Cancer. 2023. https://seer.cancer.gov/statfacts/html/cervix.html . iv McLachlan J, Boussios S, Okines A, et al. The impact of systemic therapy beyond first-line treatment for advanced cervical cancer. Clin Oncol (R Coll Radiol). 2017;29(3):153-60. v Pfaendler KS, Tewari KS. Changing paradigms in the systemic treatment of advanced cervical cancer. Am J Obstet Gynecol. 2016 Jan;214(1):22-30. doi: 10.1016/j.ajog.2015.07.022. Epub 2015 Jul 26. PMID: 26212178; PMCID: PMC5613936. vi Gennigens, C., Jerusalem, G., Lapaille, L., De Cuypere, M., Streel, S., Kridelka, F., & Ray-Coquard, I. (2022). Recurrent or primary metastatic cervical cancer: current and future treatments. ESMO open , 7 (5), 100579. https://doi-org.libproxy1.nus.edu.sg/10.1016/j.esmoop.2022.100579 . SOURCE: Genmab

临床结果上市批准临床3期

2025-03-31

·GlobeNewswire-Health Care

TIVDAK® (tisotumab vedotin) Approved by Japan Ministry of Health, Labour and Welfare for the Treatment of Advanced or Recurrent Cervical Cancer that has Progressed on or after Chemotherapy

March 27, 2025 TIVDAK® is the first and only antibody-drug conjugate (ADC) approved for patients with advanced or recurrent cervical cancer in Japan Approval is based on results from the global Phase 3 innovaTV 301 trial, in which TIVDAK demonstrated superior overall survival compared to chemotherapy Rising cervical cancer incidence and mortality rates in Japan signify need for new treatment options Genmab A/S (Nasdaq: GMAB) today announced that the Japan Ministry of Health, Labour and Welfare has approved TIVDAK® (tisotumab vedotin) for the treatment of advanced or recurrent cervical cancer that has progressed on or after cancer chemotherapy. TIVDAK is the first and only ADC to be approved for people living with cervical cancer in Japan. In recent years, cervical cancer incidence and mortality rates have increased in Japan, particularly among women under age 50.i,ii,iii Moreover, patients with recurrent or metastatic cervical cancer whose disease has progressed after first-line therapy have limited treatment options. “Patients with advanced or recurrent cervical cancer, in general, have a poor prognosis. The advent of new treatment options, especially for second-line or later treatment, is much needed,” said Aikou Okamoto, M.D., Ph.D., Chief Professor, Department of Obstetrics and Gynecology at The Jikei University School of Medicine. “Cervical cancer treatment has advanced in recent years, but it is very meaningful that the approval of tisotumab vedotin as an ADC has increased the number of treatment options with a new mechanism of action that is expected to prolong overall survival. This is good news for patients and healthcare professionals.” The approval is based on data from the randomized, open-label, global Phase 3 innovaTV 301 clinical trial that evaluated the efficacy and safety of TIVDAK compared to chemotherapy in patients with advanced or recurrent cervical cancer who were previously treated with chemotherapy. The trial included 502 patients, 101 of which were Japanese. The trial met its primary endpoint of overall survival (OS), demonstrating a 30% reduction in risk of death (HR: 0.70 [95% CI: 0.54-0.89], two-sided p=0.0038) compared to chemotherapy. Median OS was 11.5 months [95% CI: 9.8-14.9] among patients treated with TIVDAK compared to 9.5 months [95% CI: 7.9-10.7] for patients who received chemotherapy. Secondary endpoints of progression-free survival (PFS) and confirmed objective response rate (ORR) were also met. Adverse drug reactions occurred in 219 (87.6%) of 250 patients (including 50 Japanese patients) treated with TIVDAK. The most common (≥20%) adverse reactions included conjunctivitis (n=76; 30.4%), nausea (n=73; 29.2%), peripheral sensory neuropathy (n=67; 26.8%), alopecia (n=61; 24.4%), and epistaxis (n=57; 22.8%), at the data cutoff date of July 24, 2023. “As a company, we understand the urgent need for patients with advanced cervical cancer whose disease has progressed,” said Judith Klimovsky, M.D., Executive Vice President and Chief Development Officer of Genmab. “This approval marks an important step forward in transforming the treatment paradigm in Japan, ultimately bringing new hope and possibility to patients and their loved ones.” The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating tisotumab vedotin versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who received one or two prior systemic regimens in the recurrent or metastatic setting. Patients with recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma or adenosquamous histology, and disease progression during or after treatment with chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint was overall survival. The main secondary outcomes were progression-free survival and objective response rate. The study was conducted by Seagen, which was acquired by Pfizer in December 2023, in collaboration with Genmab, European Network of Gynaecological Oncological Trial Groups (ENGOT, study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG) Foundation (study number GOG 3057), as well as other global gynecological oncology cooperative groups. For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov. Tisotumab vedotin (approved under the brand name TIVDAK® in the U.S. and Japan) is an antibody-drug conjugate (ADC) composed of Genmab’s human monoclonal antibody directed to tissue factor (TF) and Pfizer’s ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Nonclinical data suggest that the anticancer activity of tisotumab vedotin is due to the binding of the ADC to TF-expressing cancer cells, followed by internalization of the ADC-TF complex and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity. Tisotumab vedotin is co-developed and co-commercialized globally by Genmab and Pfizer, under an agreement in which the companies share costs and profits. With respect to the commercialization of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer, Genmab leads commercialization in Japan and all other regions globally, outside the United States and China. In these regions, Pfizer partners with Genmab and Zai Lab, respectively, on commercialization. Genmab is an international biotechnology company with a core purpose of guiding its unstoppable team to strive toward improving the lives of patients with innovative and differentiated antibody therapeutics. For more than 25 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational, quantitative and data sciences, resulting in a proprietary pipeline including bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators and effector function-enhanced antibodies. By 2030, Genmab’s vision is to transform the lives of people with cancer and other serious diseases with knock-your-socks-off (KYSO®) antibody medicines. Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. i Cancer Statistics Cervix, National Cancer Center, Cancer Information Service, ganjoho.jp/reg_stat/statistics/stat/cancer/17_cervix_uteri.html#anchor1. Accessed 14 Feb. 2025. ii Trends in Cancer Incidence and Mortality Rates, World Health Organization, gco.iarc.fr/overtime/en. Accessed 14 Feb. 2025. iii For Correct Understanding of Cervical Cancer and HPV Vaccine, Japan Society of Obstetrics and Gynecology, www.jsog.or.jp/citizen/5765/. Accessed 14 Feb. 2025. The content above comes from the network. if any infringement, please contact us to modify.

临床结果上市批准抗体药物偶联物

2025-03-28

·抗体圈

最有料的ADC Biotech，准备起爆

ADC药物来到收获期。第一三共德曲妥珠单抗2024年全球销售约38亿美元，有机构预计其2026年有望冲击75亿美金，重磅炸弹威力尽显。国内ADC Biotech离收获期也正在越来越近。3月27日，乐普生物发布2024年业绩公司公告：公司实现了收入3.68亿，同比增长63.2%，其中普特利单抗销售大幅放量，实现3亿销售收入，约为2023年1.01亿的3倍。值得注意的是，过去一年里乐普生物通过产品商业化放量、融资配售等表现，延长了公司的现金流管道，公司的现金及等价物与2023年基本持平（以及MRG007在2025年初出海进一步增厚公司现金流储备）；另外，随着PD-1普特利单抗商业化逐渐成熟，公司未来有更多的经验和资源蓄力EGFR ADC产品MRG003商业化。乐普生物业绩数据的渐入佳境只是浅层表象，2025年公司将迎来密集的催化因子，真正的商业化爆发期和新一波的出海浪潮即将到来。01003冲刺商业化：适应症扩容在即在FIC EGFR ADC管线MRG003近期历经了一次申报波折，这仅稍稍拖慢了商业化步伐，不影响这款国内FIC大单品的获批终局；而MRG003更强的催化，也将在今年到来。MRG003在鼻咽癌（NPC）的优势地位正在确立，其已经集齐了FDA关于复发性或转移性鼻咽癌（R/M NPC）的突破性疗法、孤儿药和快速通道资格。目前，MRG003等待CDE审批的适应症为二线及以上鼻咽癌，未来MRG003冲击一线治疗扩大适应症空间也不在话下。乐普生物在2024 ESMO亚洲年会上最新公布的MRG003联合PD-1普特利单抗治疗R/M NPC二期数据显示：在30例接受治疗患者中（29例为PD-(L)1抗体治疗后进展），ORR达到了66.7%，DCR达到了93.3%，6个月PFS率为76.2%，其中2例患者CR、18例患者PR，疗效非常惊艳；当前2024 CSCO指南一线治疗鼻咽癌为PD-1联合吉西他滨联合顺铂的ORR普遍在60-80%不等，≥3级不良反应率超过80%。对比之下，若未来MRG003联合PD-1普特利单抗挑战一线NPC治疗将有着很高的成功率。MRG003更大的预期差在头颈鳞癌（HNSCC）。头颈癌是全球第6大最常见的恶性肿瘤，据GLOBOCAN估计全球每年新发病例约89万，占所有癌症类型的4.5%。而HNSCC占头颈癌的90%；目前局部晚期的HNSCC主要治疗手段是同步放疗化疗，但超过一半患者接受治疗后3年内复发，复发或转移患者5年生存率不足5%，一线治疗为PD-1联合疗法，二线治疗为EGFR西妥昔单抗联合疗法，再后线缺乏治疗手段。乐普生物在2023 ESMO大会的最新头颈癌二期临床数据显示：PD-1/L1抗体耐药二线头颈癌患者中，接受2.3mg/kg MRG003治疗组ORR为43%、DCR为86%，mPFS为4.2个月，mOS为11.3个月（趋近于一线疗法的OS），相比PD-1/L1抗体在同类病人仅有6-7个月的OS，疗效极具突破性。2024 ASCO乐普生物公布一项MRG003联合普特利单抗治疗鼻咽癌和头颈鳞癌的 I/II 期临床数据，其中5例可评估一线头颈癌患者中，3例PR，1例SD，ORR和DCR分别为60%和80%。尽管样本量不大，但考虑到KEYNOTE-048研究显示K药联合化疗一线治疗头颈癌ORR为36%，MRG003联合普特利单抗初期数据接近将ORR翻倍，颠覆性或迭代性的潜力毋庸置疑。值得期待的是，MRG003 NPC注册性IIb期研究结果入选2025年ASCO大会的LBA（重磅研究摘要）口头汇报，LBA每年的入选概率大概不到0.5%，进一步验证了这个分子的巨大潜力。同时2025年下半年MRG003联合普特利单抗治疗一线头颈癌的三期临床数据也即将读出，若能够延续早期数据优异性，出海潜力拉满。MRG003的商业化前景一片光明。从过往解决未满足临床需求的唯一性或差异化创新药的商业化作为参考，基本上均能实现上市快速放量、至少成为国内或全球潜力重磅炸弹的目标；国内案例看，复宏汉霖的PD-1斯鲁利单抗瞄准小细胞肺癌未满足临床需求，刷新了ES-SCLC免疫治疗患者mOS记录；海外案例看，艾伯维的FRα ADC填补了卵巢癌后线治疗空白，上市首年销售2亿美元。同样，MRG003未来上市之后不仅填补二线及后线鼻咽癌治疗的空白，其同类最佳的疗效潜质有望刷新全线免疫治疗患者的OS获益；头颈癌领域，MRG003提供给二线及后线患者一种全新疗效更优的治疗选择，并且MRG003与PD-1联用有望冲击一线治疗地位，同样有望刷新全线免疫治疗患者的OS获益；未来，MRG003将有望成为二线及后线鼻咽癌、头颈癌治疗的“金标准”。鼻咽癌、头颈癌虽然市场空间不如肺癌、乳腺癌等大适应症，填补临床空白和迭代标准治疗带来的市场潜力不容小觑。由于早期鼻咽癌患5年者生存率极高，数据统计国内存量的一二线鼻咽癌患者至少超过20万人，这均为MRG003潜在治疗患者；2023年国内头颈癌治疗药物市场约45亿元，主要由化疗、PD-1免疫治疗药物占据。海外方面，美林则是对Merus双抗Petosemtamab治疗一线、二线后头颈癌的销售峰值分别给到16亿美元、9.47亿美元；可见，MRG003无论在国内或者海外仅凭鼻咽癌、头颈癌这两个适应症，至少有望冲击15亿美元的市场价值（国内海外二八开）。02手握新型ADC梯队蓄势待发踏入商业化蓄力期的同时，乐普生物新型ADC梯队也开始发力。近年来，乐普生物ADC出海交易不断，2023年乐普生物/康诺亚的CLDN18.2 ADC产品CMG901以总额11.88亿美元授权给阿斯利康，2025年则是将临床前ADC管线MRG007以超12亿美元授权给ArriVent BioPharma，ADC领域创新能力被MNC和海外资本充分认可。为了创造出更多FIC、BIC的创新ADC产品，乐普生物还开发了新一代ADC研发平台Hi-TOPi。Hi-TOPi针对过去和目前这一代ADC产品存在的问题对各个ADC零部件做了全面的“升级”，平台能筛选出亲和力更强、内吞更快的抗体发挥ADC靶向能力，其次则是采用了血液高稳定性并在肿瘤高效释放的Linker，Payload是新型TOP1抑制剂而非Pgp的底物（具有克服耐药性的潜力），未来Hi-TOPi将成为乐普生物新一代ADC孵化池。乐普生物最新进入临床的MRG006A管线便是Hi-TOPi平台的产物，MRG006A是一款全球首创的GPC3 ADC，采用对GPC3亲和力高、内吞快的抗体，同时Payload为新型TOP1抑制剂（非Pgp底物），DAR为8；GPC3是一个超70%肝癌组织高表达的靶点，但在正常组织几乎不表达，是一个非常适合作为ADC开发的靶点。MRG006A临床前研究显示：其在多个不同GPC3表达水平的肝癌CDX模型和PDX模型中均表现出强大且剂量依赖的抗肿瘤功能。将视角拉回来，乐普生物在研管线中进度靠前且有望接下来兑现出海潜力的ADC莫过于靶向TF的MRG004A。组织因子（TF）靶点本身便是一个潜在市场空间较大的ADC开发靶点，其在多种实体瘤中存在阳性表达，包括宫颈癌（阳性率100%）、非小细胞肺癌、卵巢癌、前列腺癌、胰腺癌等，这定位了其开发上限；目前，全球TF靶点进入临床药物屈指可数，唯一获批的是辉瑞的TF ADC产品Tivdak，2024年销售1.31亿美元，乐普生物MRG004A目前进度全球第二，处于I/II期临床的数据整理阶段，未来一年有望进入注册三期临床。目前MRG004A处于I/II期临床探索在TF阳性实体瘤的潜力（涵盖胰腺癌、三阴性乳腺癌、宫颈癌等），其中MRG004A在被称为“癌王”胰腺癌适应症上展现了超强的潜力。MRG004A在ASCO大会公布的I/II期数据显示，在2.0mg/kg剂量组的12名可评估胰腺癌患者中，ORR为33.3%，DCR为83.3%；在TF高表达（TF≥50%）且前线治疗线数2线以内的胰腺癌患者中，ORR为80%，DCR为100%。要知道，胰腺癌的5年生存率极低，并且以二线标准治疗化疗为例其有效率在6-17%，PFS只有2-3.5个，缺乏有效的治疗方案。MRG004A无疑提供了一个全新的治疗方案，并且尤其在胰腺癌TF高表达的部分人群中拥有巨大的潜力，由此MRG004A也获得FDA授予在胰腺癌治疗上的孤儿药认定。对于胰腺癌这种全球性难题，填补临床空白的创新有宽广的定价区间和巨大的市场潜力，例如Revolution公司RMC-6236仅在PDAC适应症早期临床展现出初步潜力，市值便一度突破百亿美元，Jefferies预计RMC-6236仅在PDAC适应症就有约50亿美元的市场机会。而对于MRG004A，除了胰腺癌适应症外其在三阴乳腺癌、宫颈癌小样本临床数据均展现不俗潜力，未来市场空间广阔，有望在读出早期数据后放大出海价值。与阿斯利康合作的CMG901早在2024年4月启动了全球胃癌三期临床，公司有望在未来三期读出数据后收获源源不断的临床监管里程碑及后续销售分成；另外，CD20 ADC产品MRG001在血液瘤中大适应症复发难治型DLBCL的早期临床中也展现出不俗潜力，有望解决后线DLBCL患者的未满足临床需求。不难看出，乐普生物正手握一大批拥有出海潜力的ADC管线，能够在未来为公司提供源源不断的现金流和持续拓展公司的价值上限。03手握最佳联用组合下一个免疫治疗时代离不开IO、ADC等迭代创新分子，同样也离不开联合用药。随着更多“PD-1+ADC”组合开始冲击实体瘤一线治疗，有“PD-1+溶瘤病毒”组合在实体瘤全球三期展现迭代性疗效，可以确认未来实体瘤免疫治疗的一线疗法离不开抗体、ADC或溶瘤病毒等的联用，目前已经有不少企业尝试双抗+ADC的组合。据Hanson Wade 数据库显示，2022年启动的ADC临床研究达到244项，联合用药有126项超过临床数量的一般，其中ADC+IO的联用达到58项，联合用药显然是一个大趋势。乐普生物显然深谙下个时代的趋势，公司在每一个关键“部件”领域都有布局，涵盖PD-1、TCE多抗、ADC、溶瘤病毒，尽显公司布局前瞻性。在联用布局上，乐普生物区别于其他Biotech的一大差异化优势在于，公司拥有稀缺的溶瘤病毒资产CG0070权益，拥有潜在BIC的潜力。CG0070是一种基因修饰的5型腺病毒（Ad5）溶瘤病毒，溶瘤病毒最大优点在于“百搭性”，其能够作为免疫激活和药物递送的工具。从乐普生物合作伙伴CG Oncology公布最新临床BOND-003数据显示，单药治疗110例高危卡介苗（BCG）无反应的非肌层浸润性膀胱癌（NMIBC）患者中，110名患者中有82例患者实现了完全缓解（CR率74.5%），1年完全缓解率为46%；而在阶段更早的CG0070联合K药二期临床CORE-001数据显示，35名患者中29名实现了完全缓解（CR率82.9%），12个月时的CR率为57.1%。CG0070的海外数据，一方面证实了该疗法潜在同类最佳的潜力（与强生TAR- 200 疗效相近），CG0070有望凭借BOND-003的数据支持获得美国FDA的批准，另一方面也证明溶瘤病毒联用IO疗法有着优越的潜在价值。。乐普生物从引进CG0070以来一直在等待其注册临床的进展，随着今年CG0070海外顺利成药验证和申报上市，乐普生物即可在国内实现简洁快速的桥接临床和推动药物上市，亦能占到国内PD-1联合溶瘤病毒治疗NMIBC的先机，在国内联合治疗史上又是浓墨重彩的一笔。另外，乐普生物早早的开展了普特利单抗分别联用MRG003和MRG002分别探索EGFR阳性实体瘤、HER2阳性实体瘤的二期临床，EGFR、HER2两个靶点均为在多种实体瘤上高表达的热门靶点，这样的联用布局不仅能进一步探索组合在各类适应症上的广泛潜力，同时能够帮助过去单药ADC治疗突破后线治疗的桎梏推进前线治疗，可谓一箭双雕；普特利单抗和MRG003的联用布局已经前述2024 ESMO的鼻咽癌二期临床确证了“1+1＞2”的显著疗效，而2025H2头颈癌三期数据验证将进一步打开该联用疗法的市场空间。从联用方向角度来看，乐普生物的上限走在国内Biotech的前列，公司不仅有已商业化的PD-1单抗，同时手握多个实体瘤高表达广谱靶点的ADC管线，以及稀缺的溶瘤病毒产品权益，公司有望通过合理创新的药物组合机制，在更多如乳腺癌、膀胱癌、头颈癌等大适应症或差异化未满足临床需求去挑战早线治疗，若挑战成功将收获巨大市场份额，这里甚至还没有考虑到公司早研新型TCE分子的组合。结语：乐普生物正处于一个准备加速的蓄力期，MRG003的头颈癌三期数据或国内的商业化审批都能将公司带上一个全新的高度，这是深耕未满足临床需求和同类首创分子的正向馈赠；同时，公司前瞻性布局的一众新型ADC分子和联合用药组合将在未来随时迸发出超预期的临床及出海价值，这家低调的Biotech正在向市场展示强大研发能力和其蕴含磅礴的出海价值；至于价值突破，也只是时间问题。识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

抗体药物偶联物孤儿药CSCO会议临床2期引进/卖出

100 项与替索单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	替索单抗	-	-

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
晚期宫颈癌	日本	Genmab, Inc.	2025-03-27
转移性宫颈癌	中国澳门	再鼎医药有限公司	2024-08-06
复发性宫颈癌	中国澳门	再鼎医药有限公司	2024-08-06
宫颈癌	美国	Seagen, Inc.	2021-09-20

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
子宫颈转移癌	临床3期	美国	Genmab A/S	2021-02-22
子宫颈转移癌	临床3期	中国	Genmab A/S	2021-02-22
子宫颈转移癌	临床3期	日本	Genmab A/S	2021-02-22
子宫颈转移癌	临床3期	阿根廷	Genmab A/S	2021-02-22
子宫颈转移癌	临床3期	奥地利	Genmab A/S	2021-02-22
子宫颈转移癌	临床3期	比利时	Genmab A/S	2021-02-22
子宫颈转移癌	临床3期	巴西	Genmab A/S	2021-02-22
子宫颈转移癌	临床3期	加拿大	Genmab A/S	2021-02-22
子宫颈转移癌	临床3期	捷克	Genmab A/S	2021-02-22
子宫颈转移癌	临床3期	丹麦	Genmab A/S	2021-02-22

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适应症

分期

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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


NCT04697628 (innovaTV 301, Company_Website) 人工标引	临床3期	宫颈癌	-	TIVDAK	膚範衊鏇範顧觸構糧艱(鹽餘積衊鏇鹽簾遞製築) = 遞膚夢夢餘構衊鏇憲襯鹹壓鹽壓醖顧鏇範繭鬱 (繭鑰獵鑰鹽憲窪糧築憲 )	积极	2025-01-15
				Chemotherapy	膚範衊鏇範顧觸構糧艱(鹽餘積衊鏇鹽簾遞製築) = 網網夢積襯餘網鬱夢願鹹壓鹽壓醖顧鏇範繭鬱 (繭鑰獵鑰鹽憲窪糧築憲, 6.0 ~ NR)
NCT04697628 (innovaTV 301/ENGOT-cx12/GOG 3057 \| SGNTV-003 \| GOG-3057 \| innovaTV 301 \| ENGOT-cx12 \| innovaTV 301/ENGOT-cx12/GOG-3057, CTgov)	临床3期	子宫颈转移癌	502	tisotumab vedotin (Tisotumab Vedotin)	壓齋淵願構餘積艱襯餘(鹹壓齋艱鑰簾膚醖艱襯) = 構願願艱遞積鑰構蓋衊壓憲觸廠蓋繭獵獵憲願 (窪齋鹹鏇範襯簾糧窪蓋, 獵廠繭窪醖壓選壓範選 ~ 獵願遞範夢顧網繭窪鹹) 更多	-	2024-08-09
				pemetrexed+vinorelbine+Gemcitabine+irinotecan+Topotecan (Chemotherapy)	壓齋淵願構餘積艱襯餘(鹹壓齋艱鑰簾膚醖艱襯) = 鏇築鹹襯遞獵夢選鑰鬱壓憲觸廠蓋繭獵獵憲願 (窪齋鹹鏇範襯簾糧窪蓋, 憲構糧願範醖鑰積糧齋 ~ 築衊襯醖獵製糧範廠積) 更多
NCT04697628 (innovaTV 301, Pubmed) 人工标引	临床3期	复发性宫颈癌二线 \| 三线	502	Tisotumab vedotin	糧獵淵製範鬱網網襯鏇(窪觸鬱淵構範廠憲觸齋) = 衊顧襯獵簾製構鏇齋糧築鏇獵網蓋觸願衊願遞 (鹹齋鏇構艱蓋選餘鬱壓, 9.8 ~ 14.9) 更多	积极	2024-07-04
				Chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed)	糧獵淵製範鬱網網襯鏇(窪觸鬱淵構範廠憲觸齋) = 艱衊鏇衊獵齋襯獵積襯築鏇獵網蓋觸願衊願遞 (鹹齋鏇構艱蓋選餘鬱壓, 7.9 ~ 10.7) 更多
NCT03485209 (innovaTV 207, ASCO2024) 人工标引	临床2期	头颈部鳞状细胞癌	40	Tisotumab vedotin	築艱窪糧艱鏇艱觸願觸(夢淵鹽觸鬱鏇獵壓選淵) = 獵遞鏇網鑰鏇鹹簾蓋淵壓鑰鑰鬱蓋鏇壓壓襯淵 (製醖窪鏇窪鹹選鑰築衊, 18.6 ~ 49.1) 更多	积极	2024-05-24
				Tisotumab vedotin (≤2 prior lines)	築艱窪糧艱鏇艱觸願觸(夢淵鹽觸鬱鏇獵壓選淵) = 積獵餘淵選餘夢廠餘糧壓鑰鑰鬱蓋鏇壓壓襯淵 (製醖窪鏇窪鹹選鑰築衊, 21.1 ~ 61.3) 更多
NCT04697628 (ENGOT-cx12 \| GOG-3057 \| innovaTV 301, ASCO2024) 人工标引	临床3期	宫颈癌二线 \| 三线	502	Tisotumab vedotin (TV)	鹽遞餘積築齋餘鏇願顧(鑰膚艱衊顧願膚範憲餘) = 網構積鬱蓋鏇獵糧壓製鏇壓憲築壓襯觸膚製齋 (顧膚遞窪窪繭餘製衊糧, 13.3 ~ 23.1) 更多	积极	2024-05-24
				Chemotherapy	鹽遞餘積築齋餘鏇願顧(鑰膚艱衊顧願膚範憲餘) = 憲衊壓築選鹽鏇齋餘築鏇壓憲築壓襯觸膚製齋 (顧膚遞窪窪繭餘製衊糧, 2.8 ~ 8.8) 更多
NCT04697628 (innovaTV 301 \| ENGOT-Cx12 \| GOG-3057, ESGO2024) 人工标引	临床3期	宫颈癌二线 tissue factor	502	Tisotumab vedotin	艱壓顧選蓋範淵鹹鹹獵(蓋製糧鹽鹽積窪夢襯廠) = 衊膚鬱簾膚憲醖齋淵窪觸壓鬱觸積夢遞壓衊觸 (齋製鑰鏇醖壓鑰網廠襯, 9.8 ~ 14.9) 更多	积极	2024-03-10
				investigator’s choice of chemotherapy	艱壓顧選蓋範淵鹹鹹獵(蓋製糧鹽鹽積窪夢襯廠) = 艱衊觸憲糧衊糧衊繭蓋觸壓鬱觸積夢遞壓衊觸 (齋製鑰鏇醖壓鑰網廠襯, 7.9 ~ 10.7) 更多
NCT03786081 (innovaTV 205/GOG-3024/ENGOT-cx8, Pubmed \| J Clin Oncol)	临床1/2期	子宫颈转移癌一线 \| 三线 tissue factor	142	Tisotumab vedotin + Pembrolizumab	築積範餘壓製醖選餘醖(糧廠鑰顧廠艱積廠衊鏇) = 鹽淵網鬱選壓醖襯繭範衊獵艱顧觸窪鏇蓋壓憲 (蓋襯築選憲蓋夢齋窪鑰, 23.7 ~ 59.4) 更多	积极	2023-12-20
				Tisotumab vedotin + Carboplatin	築積範餘壓製醖選餘醖(糧廠鑰顧廠艱積廠衊鏇) = 觸鏇積鏇繭齋簾鑰遞獵衊獵艱顧觸窪鏇蓋壓憲 (蓋襯築選憲蓋夢齋窪鑰, 36.4 ~ 71.9) 更多
NCT04697628 (innovaTV 301 \| SGNTV-003 \| GOG-3057 \| ENGOT-cx12, ESMO 12023 \| ESMO 22023) 人工标引	临床3期	宫颈癌三线 \| 二线	502	Tisotumab vedotin	淵襯觸廠醖襯窪衊淵簾(壓遞繭觸憲鑰顧願鏇夢) = 鏇鹹製積鏇壓網鹹鹽衊襯衊鏇築醖艱鬱壓憲簾 (鏇餘窪鹽獵繭膚蓋鹽鬱, 9.8 ~ 14.9) 更多	积极	2023-10-22
				Investigator's choice of chemotherapy	淵襯觸廠醖襯窪衊淵簾(壓遞繭觸憲鑰顧願鏇夢) = 顧選衊鏇積夢衊遞獵餘襯衊鏇築醖艱鬱壓憲簾 (鏇餘窪鹽獵繭膚蓋鹽鬱, 7.9 ~ 10.7) 更多
NCT04697628 (innovaTV 301, NEWS) 人工标引	临床3期	宫颈癌一线	-	Tivdak	醖夢獵構鏇獵願窪築廠(製廠製窪鬱壓糧糧衊襯) = 在一线治疗期间或治疗后疾病发生进展的复发性或转移性宫颈癌患者中，与单独化疗相比，接受其“first-in-class”抗体偶联药物（ADC）Tivdak（tisotumab vedotin）患者的OS显著改善網糧廠鹽壓觸糧製淵製 (獵選夢鏇鹽觸艱夢願糧 ) 达到更多	积极	2023-09-06
				chemotherapy
NCT03657043 (CTgov)	临床2期	铂类耐药性原发性腹膜癌 \| 腹膜癌 \| 铂耐药性卵巢癌 ... 更多	98	3Q4W (Safety Run-In 0.9 mg/kg 3Q4W)	獵築觸鏇鏇壓顧鏇獵觸 = 製鬱齋觸夢壓範鑰餘膚壓憲構顧網網鹽齋選繭 (鹹齋製簾艱鹹齋廠憲餘, 淵鹽鑰鏇鑰壓遞鑰鹽鹽 ~ 憲窪餘觸鹹築鏇鹽鏇膚) 更多	-	2023-05-06
				3Q4W (Safety Run-In 1.2 mg/kg 3Q4W)	獵築觸鏇鏇壓顧鏇獵觸 = 衊窪醖鬱獵齋膚簾窪網壓憲構顧網網鹽齋選繭 (鹹齋製簾艱鹹齋廠憲餘, 繭構衊壓鑰簾鏇繭網憲 ~ 壓繭鑰廠鬱築構艱鏇鬱) 更多