COPENHAGEN, Denmark--(BUSINESS WIRE)--Genmab A/S (Nasdaq: GMAB) and Pfizer Inc. (NYSE: PFE) announced today the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for TIVDAK® (tisotumab vedotin-tftv) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

丹麦哥本哈根--（商业新闻短讯）--Genmab A/S（纳斯达克：GMAB）和辉瑞公司（纽约证券交易所：PFE）今天宣布，美国食品和药物管理局（FDA）已批准TIVDAK®（tisotumab vedotin tftv）的补充生物制剂许可证申请（sBLA），用于治疗化疗期间或之后疾病进展的复发或转移性宫颈癌患者。

This FDA action converts the September 2021 accelerated approval of TIVDAK to a full approval. TIVDAK is the first antibody-drug conjugate (ADC) with demonstrated overall survival data to be granted full FDA approval in this patient population..

FDA的这一行动将2021年9月对TIVDAK的加速批准转变为全面批准。TIVDAK是第一个抗体-药物偶联物（ADC），其总体生存数据已被证明可在该患者群体中获得FDA的全面批准。。

The approval is based on results from the global, randomized, Phase 3 innovaTV 301 clinical trial (NCT04697628), in which TIVDAK met its primary endpoint of overall survival (OS) in patients with previously treated recurrent or metastatic cervical cancer compared to chemotherapy. Secondary endpoints of progression-free survival (PFS) and a confirmed objective response rate (ORR) were also met.

该批准基于全球随机3期innovaTV 301临床试验（NCT04697628）的结果，在该试验中，与化疗相比，TIVDAK达到了先前治疗的复发或转移性宫颈癌患者总生存期（OS）的主要终点。还满足了无进展生存期（PFS）和确诊客观缓解率（ORR）的次要终点。

In October 2023, results from the innovaTV 301 study were initially disclosed during the Presidential Symposium at the European Society of Medical Oncology (ESMO) Congress..

2023年10月，innovaTV 301研究的结果最初在欧洲肿瘤内科学会（ESMO）大会的总统研讨会上公布。。

“As a treating physician, it is encouraging to see overall survival data among these patients and a manageable safety profile with tisotumab vedotin,” said Brian Slomovitz, M.D., Director of Gynecologic Oncology and Co-Chair of the Cancer Research Committee at Mount Sinai Medical Center, Miami Beach.

迈阿密海滩西奈山医学中心妇科肿瘤学主任兼癌症研究委员会联合主席布莱恩·斯洛莫维茨（BrianSlomovitz）医学博士说：“作为一名主治医师，看到这些患者的总体生存数据以及替索单抗vedotin的可管理安全性令人鼓舞。”。

“Treatment options for patients with advanced or recurrent cervical cancer are limited. The five-year survival rate for patients who have metastatic disease at diagnosis is less than 20% in the U.S.i There is a high unmet need for more treatment options that have demonstrated survival benefit in the contemporary treatment landscape.

“晚期或复发性宫颈癌患者的治疗选择有限。在美国，诊断为转移性疾病的患者的五年生存率不到20%。在当代治疗领域，对更多治疗选择的需求尚未得到满足，这些治疗选择显示出生存益处。

The approval of tisotumab vedotin brings us a step closer to fulfilling that need.”.

tisotumab vedotin的批准使我们离满足这一需求又近了一步。”。

The innovaTV 301 study met its primary endpoint of OS, demonstrating a 30% reduction in the risk of death compared with chemotherapy (Hazard ratio [HR]: 0.70 [95% CI: 0.54, 0.89], two-sided p=0.0038ii). Median OS for patients treated with TIVDAK was 11.5 months [95% CI: 9.8-14.9] versus chemotherapy 9.5 months [95% CI: 7.9-10.7]..

innovaTV 301研究达到了OS的主要终点，与化疗相比，死亡风险降低了30%（风险比[HR]:0.70[95%CI:0.54,0.89]，双侧p=0.0038ii）。TIVDAK治疗患者的中位OS为11.5个月[95%可信区间：9.8-14.9]，而化疗为9.5个月[95%可信区间：7.9-10.7]。。

“The full FDA approval of TIVDAK represents a significant achievement for women with recurrent and metastatic cervical cancer, reinforcing TIVDAK as a treatment option that has proven to extend survival in patients whose disease has advanced after initial treatments,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

Genmab首席执行官Jan van de Winkel博士说：“FDA对TIVDAK的全面批准代表了复发性和转移性宫颈癌女性的一项重大成就，加强了TIVDAK作为一种治疗选择，已被证明可以延长初始治疗后疾病进展的患者的生存期。”。

“This milestone underscores the importance of our ongoing clinical development program to assess the full potential of tisotumab vedotin as a treatment option in other indications.”.

“这一里程碑强调了我们正在进行的临床开发计划的重要性，以评估tisotumab vedotin作为其他适应症治疗选择的全部潜力。”。

'Recurrent or metastatic cervical cancer is a particularly devastating and mostly incurable disease, and patients are in need of survival-extending treatment options,” said Chris Boshoff, M.D., Ph.D., Chief Oncology Officer, Executive Vice President at Pfizer. “Today’s full approval by the FDA reinforces the important role of TIVDAK for these patients, as the first antibody-drug conjugate with statistically significant prolonged overall survival data.”.

“复发性或转移性宫颈癌是一种极具破坏性且大多无法治愈的疾病，患者需要延长生存期的治疗选择，”辉瑞公司执行副总裁、首席肿瘤官、医学博士克里斯·博斯霍夫（ChrisBoshoff）说。“今天FDA的全面批准加强了TIVDAK对这些患者的重要作用，它是第一个抗体-药物偶联物，具有统计学上显着的延长总体生存数据。”。

The U.S. Prescribing Information for TIVDAK includes a BOXED WARNING for Ocular Toxicity as well as the following Warnings and Precautions: peripheral neuropathy, hemorrhage, pneumonitis, severe cutaneous adverse reactions, and embryo-fetal toxicity. Please see below for additional Important Safety Information..

美国TIVDAK的处方信息包括眼部毒性的盒装警告以及以下警告和注意事项：周围神经病变，出血，肺炎，严重皮肤不良反应和胚胎-胎儿毒性。有关其他重要安全信息，请参见下文。。

The safety profile of TIVDAK in innovaTV 301 was consistent with its known safety profile as presented in the U.S. prescribing information. No new safety issues were identified. The most common (≥25%) adverse reactions, including laboratory abnormalities, in patients receiving TIVDAK were hemoglobin decreased (41%), peripheral neuropathy (38%), conjunctival adverse reactions (37%), aspartate aminotransferase increased (34%), nausea (33%), alanine aminotransferase increased (30%), fatigue (28%), sodium decreased (27%), epistaxis (26%), and constipation (25%)..

TIVDAK在innovaTV 301中的安全性与美国处方信息中提供的已知安全性一致。没有发现新的安全问题。接受TIVDAK治疗的患者中最常见的（≥25%）不良反应（包括实验室异常）是血红蛋白降低（41%），周围神经病变（38%），结膜不良反应（37%），天冬氨酸转氨酶升高（34%），恶心（33%），丙氨酸转氨酶升高（30%），疲劳（28%），钠降低（27%），鼻出血（26%）和便秘（25%）。。

The sBLA application received a Priority Review Designation, which is granted by the U.S. FDA to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists.iii TIVDAK was granted accelerated approval in the U.S. by the FDA in September 2021, based on tumor response and durability of response from the innovaTV 204 pivotal Phase 2 single-arm clinical trial evaluating TIVDAK as a monotherapy in patients with previously treated recurrent or metastatic cervical cancer..

sBLA申请获得了美国FDA的优先审查指定，该指定被授予可能在治疗方面取得重大进展或可能在没有足够治疗的情况下提供治疗的药物。iii TIVDAK于2021年9月在美国获得了FDA的加速批准，基于innovaTV 204关键性2期单臂临床试验的肿瘤反应和反应持久性，该试验评估了TIVDAK作为先前治疗的复发性或转移性宫颈癌患者的单一疗法。。

“Today marks a great day for patients, especially adults battling advanced cervical cancer,” said Tamika Felder, cervical cancer patient advocate and Founder and Chief Visionary Officer, Cervivor, Inc. “This full approval opens up new treatment paths for this patient community who have long faced limited options.”.

Cervivor，Inc.宫颈癌患者倡导者、创始人兼首席远见官塔米卡·费尔德（Tamika Felder）说：“今天对患者来说是一个伟大的日子，尤其是成年人与晚期宫颈癌作斗争的日子。这项全面批准为长期面临有限选择的患者群体开辟了新的治疗途径。”。

About Cervical Cancer

关于宫颈癌

Cervical cancer remains a disease with high unmet need despite advances in effective vaccination and screening practices to prevent and diagnose pre-/early-stage cancers for curative treatment. Recurrent and/or metastatic cervical cancer is a particularly devastating and mostly incurable disease; up to 15% of adults with cervical cancer present with metastatic disease at diagnosisiv,v and, for adults diagnosed at earlier stages who receive treatment, up to 61%vi will experience disease recurrence.

尽管有效的疫苗接种和筛查实践取得了进展，以预防和诊断治疗前/早期癌症，但宫颈癌仍然是一种未满足需求的疾病。复发和/或转移性宫颈癌是一种特别具有破坏性且大多无法治愈的疾病；高达15%的宫颈癌成人在诊断时出现转移性疾病，对于接受治疗的早期诊断的成年人，高达61%的vi将经历疾病复发。

It was estimated that in 2023, more than 13,960 new cases of invasive cervical cancer were diagnosed in the U.S. and 4,310 adults would die from the disease.vii.

据估计，2023年，美国诊断出13960多例浸润性宫颈癌新病例，4310名成年人将死于该病。

About the innovaTV 301 Trial

关于innovaTV 301试用版

The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating TIVDAK® (tisotumab vedotin-tftv) 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）是一项全球性的1:1随机开放标签3期临床试验，评估TIVDAK®（tisotumab vedotin tftv）与研究者选择单药化疗（拓扑替康，长春瑞滨，吉西他滨，伊立替康或培美曲塞）治疗502例复发或转移性宫颈癌患者，这些患者在复发或转移情况下接受过一种或两种先前的全身方案。。

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.

包括患有鳞状细胞癌，腺癌或腺鳞状组织学的复发性或转移性宫颈癌患者，以及在用化疗双联+/-贝伐单抗和抗PD-（L）1药物（如果符合条件）治疗期间或之后的疾病进展。主要终点是总生存期。

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

主要次要结果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.

这项研究是由辉瑞公司于2023年12月收购的Seagen公司与Genmab、欧洲妇科肿瘤试验组网络（ENGOT，研究编号ENGOT cx-12）和妇科肿瘤组（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的。

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3阶段innovaTV 301临床试验和其他使用tisotumab vedotin的临床试验的更多信息，请访问www.clinicaltrials.gov。。

About TIVDAK® (tisotumab vedotin-tftv)

关于TIVDAK® （替索单抗韦多汀tftv）

TIVDAK (tisotumab vedotin-tftv) 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.

TIVDAK（tisotumab vedotin tftv）是一种抗体-药物偶联物（ADC），由Genmab针对组织因子（TF）的人单克隆抗体和辉瑞公司的ADC技术组成，该技术利用蛋白酶可切割接头将微管破坏剂单甲基auristatin E（MMAE）共价连接到抗体上。

Nonclinical data suggest that the anticancer activity of tisotumab vedotin-tftv 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 tftv的抗癌活性是由于ADC与表达TF的癌细胞结合，然后ADC-TF复合物内化并通过蛋白水解切割释放MMAE。MMAE破坏了活跃分裂细胞的微管网络，导致细胞周期停滞和凋亡细胞死亡。

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

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

Indication

指示

TIVDAK is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy.

TIVDAK适用于治疗化疗时或化疗后疾病进展的复发或转移性宫颈癌（r/mCC）成年患者。

About Genmab

关于Genmab

Genmab is an international biotechnology company with a core purpose guiding its unstoppable team to strive towards improving the lives of patients through innovative and differentiated antibody therapeutics. For 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, next-generation immune checkpoint modulators, effector function enhanced antibodies, and antibody-drug conjugates.

Genmab是一家国际生物技术公司，其核心宗旨是指导其不可阻挡的团队通过创新和差异化的抗体疗法努力改善患者的生活。25年来，其充满激情，创新和合作的团队发明了下一代抗体技术平台，并利用翻译，定量和数据科学，形成了一条专有的管道，包括双特异性T细胞参与者，下一代免疫检查点调节剂，效应功能增强的抗体和抗体-药物偶联物。

To help develop and deliver novel antibody therapies to patients, Genmab has formed 20+ strategic partnerships with biotechnology and pharmaceutical companies. 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..

为了帮助开发和向患者提供新型抗体疗法，Genmab与生物技术和制药公司建立了20多个战略合作伙伴关系。到2030年，Genmab的愿景是通过脱胎换骨（KYSO®）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 locations in Utrecht, the Netherlands, Princeton, New Jersey, U.S., and Tokyo, Japan. 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，在荷兰乌得勒支、美国新泽西州普林斯顿和日本东京设有办事处。有关更多信息，请访问Genmab.com，并在LinkedIn和X上关注我们。

About Pfizer Oncology

关于辉瑞肿瘤学

At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes game-changing mechanisms of action to attack cancer from multiple angles, including antibody-drug conjugates (ADCs), small molecules, bispecific antibodies and other immunotherapy biologics.

在辉瑞肿瘤学，我们处于癌症护理新时代的前沿。我们业界领先的投资组合和广泛的渠道包括从多个角度攻击癌症的改变游戏规则的行动机制，包括抗体-药物偶联物（ADC），小分子，双特异性抗体和其他免疫治疗生物制剂。

We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to extend and improve patients’ lives..

我们专注于为世界上一些最常见的癌症提供变革性治疗，包括乳腺癌，泌尿生殖系统癌症，血液肿瘤和包括肺癌在内的胸癌。在科学的推动下，我们致力于加速突破，以延长和改善患者的生活。。

About the Pfizer and Genmab Collaboration

关于辉瑞和Genmab的合作

Tisotumab vedotin is co-owned by Genmab and Pfizer, under an agreement in which the companies share costs and profits for the product on a 50:50 basis.

Tisotumab vedotin由Genmab和辉瑞共同拥有，根据协议，两家公司以50:50的比例分享产品的成本和利润。