Genmab A/S 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..

Genmab A/S 今天宣布，日本厚生劳动省已批准 TIVDAK®（tisotumab vedotin）用于治疗在癌症化疗期间或之后进展的晚期或复发性宫颈癌。TIVDAK 是日本首个也是唯一一个获批用于宫颈癌患者的 ADC 药物。

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.

近年来，日本的宫颈癌发病率和死亡率有所增加，特别是在50岁以下的女性中。i,ii,iii 此外，对于一线治疗后疾病仍然进展的复发性或转移性宫颈癌患者，其治疗选择有限。

“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.

“一般来说，晚期或复发性宫颈癌患者的预后较差。新的治疗选择的出现，特别是二线或后期治疗，是非常必要的。” 日本医科大学妇产科主任、医学博士Aikou Okamoto教授表示。

“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.”.

“近年来，宫颈癌的治疗取得了一定的进展，但有意义的是，tisotumab vedotin作为一种抗体药物偶联物（ADC）的获批增加了具有新作用机制的治疗选择，有望延长总生存期。这是患者和医疗专业人士的好消息。”

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.

该批准基于随机、开放标签、全球 III 期 innovaTV 301 临床试验的数据，该试验评估了 TIVDAK 在既往接受过化疗的晚期或复发性宫颈癌患者中的疗效和安全性，并与化疗进行了比较。试验共纳入 502 名患者，其中 101 名为日本患者。

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.

该试验达到了其主要终点——总生存期（OS），与化疗相比，死亡风险降低了30%（HR：0.70 [95% CI：0.54-0.89]，双侧p=0.0038）。接受TIVDAK治疗的患者中位OS为11.5个月 [95% CI：9.8-14.9]，而接受化疗的患者中位OS为9.5个月 [95% CI：7.9-10.7]。

Secondary endpoints of progression-free survival (PFS) and confirmed objective response rate (ORR) were also met..

无进展生存期（PFS）和确认的客观缓解率（ORR）次要终点也已达成。

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..

在接受TIVDAK治疗的250名患者（包括50名日本患者）中，有219名患者（87.6%）发生了药物不良反应。最常见的（≥20%）不良反应包括结膜炎（n=76；30.4%）、恶心（n=73；29.2%）、外周感觉神经病变（n=67；26.8%）、脱发（n=61；24.4%）和鼻出血（n=57；22.8%），数据截止日期为2023年7月24日。

“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.”.

“作为一家公司，我们理解那些疾病已经恶化的晚期宫颈癌患者的迫切需求，”Genmab执行副总裁兼首席开发官Judith Klimovsky博士说道。“这一批准标志着在日本转变治疗模式的重要一步，最终为患者及其亲人带来新的希望和可能性。”

About the innovaTV 301 Trial

关于innovaTV 301试验

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..

innovaTV 301试验（NCT04697628）是一项全球性、1:1随机、开放标签的3期临床试验，评估了替索妥单抗维多汀与研究者选择的单药化疗（拓扑替康、长春瑞滨、吉西他滨、伊立替康或培美曲塞）在502名复发或转移性宫颈癌患者中的疗效，这些患者在复发或转移性环境中接受过一到两种先前的系统治疗方案。

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.

符合条件的患者包括那些患有复发性或转移性宫颈癌（具有鳞状细胞、腺癌或腺鳞癌组织学特征）且在接受含贝伐单抗（bevacizumab）的双药化疗方案 +/- 贝伐单抗和抗PD-(L)1药物治疗期间或之后疾病进展的患者（如果符合条件）。主要终点是总生存期。

The main secondary outcomes were progression-free survival and objective response rate..

主要的次要结局是无进展生存期和客观缓解率。

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.

该研究由 Seagen 开展，Seagen 于 2023 年 12 月被辉瑞收购，与 Genmab、欧洲妇科肿瘤试验组网络 (ENGOT，研究编号 ENGOT cx-12)、妇科肿瘤组 (GOG) 基金会 (研究编号 GOG 3057) 以及其他全球妇科肿瘤合作组合作进行。

For more information about the Phase 3 innovaTV 301 clinical trial and other clinical trials with tisotumab vedotin, please visit www.clinicaltrials.gov..

有关第三阶段innovaTV 301临床试验和tisotumab vedotin其他临床试验的更多信息，请访问www.clinicaltrials.gov。

About Tisotumab Vedotin

关于Tisotumab Vedotin

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.

Tisotumab vedotin（在美国和日本以品牌名TIVDAK®获批）是一种抗体药物偶联物（ADC），由Genmab公司针对组织因子（TF）的人源单克隆抗体与辉瑞的ADC技术组成，该技术利用一种蛋白酶可切割的连接子，将微管破坏剂单甲基澳瑞他汀E（MMAE）共价连接到抗体上。

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.

非临床数据表明，tisotumab vedotin的抗癌活性是由于ADC与表达TF的癌细胞结合，随后ADC-TF复合物内化并通过蛋白水解裂解释放MMAE。MMAE破坏活跃分裂细胞的微管网络，导致细胞周期停滞和细胞凋亡死亡。

In vitro, tisotumab vedotin also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity..

在体外，tisotumab vedotin 还介导抗体依赖性细胞吞噬作用和抗体依赖性细胞毒性。

About the Pfizer and Genmab Collaboration

辉瑞与Genmab合作简介

Tisotumab vedotin is co-developed and co-commercialized globally by Genmab and Pfizer, under an agreement in which the companies share costs and profits.

Tisotumab vedotin 由 Genmab 和 Pfizer 根据一项协议在全球共同开发和共同商业化，两家公司分担成本并分享利润。

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. .

关于tisotumab vedotin在既往治疗过的复发性或转移性宫颈癌中的商业化，Genmab在日本及美国和中国以外的所有其他全球地区主导商业化。在这些区域，辉瑞分别与Genmab和再鼎医药合作进行商业化。

About Genmab

关于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.

Genmab是一家国际生物技术公司，其核心目标是引导其不懈努力的团队，通过创新和差异化的抗体疗法改善患者的生活。在过去的25年多时间里，其充满热情、创新力和协作精神的团队发明了下一代抗体技术平台，并利用转化科学、定量科学和数据科学，构建了一个包括双特异性T细胞接合器、抗体药物偶联物、下一代免疫检查点调节剂和效应功能增强型抗体的专有研发管线。

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. .

到2030年，Genmab的愿景是通过令人惊叹（KYSO®）的抗体药物改变癌症和其他严重疾病患者的生活。

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.

Genmab 成立于1999年，总部位于丹麦哥本哈根，在北美、欧洲和亚太地区均有业务。欲了解更多信息，请访问 Genmab.com 并在 LinkedIn 和 X 上关注我们。