tissue factor

Genmab has announced that the European Commission (EC) has approved Tivdak (tisotumab vedotin) to treat recurrent or metastatic cervical cancer. The drug has been specifically authorised to treat adults experiencing disease progression on or after systemic therapy, and is now the first antibody-drug conjugate (ADC) to be approved in the EU for recurrent or metastatic cervical cancer. Despite progress in cervical cancer prevention and early detection, the disease is the fourth most common cancer in women globally, with approximately 660,000 cases diagnosed in 2022 alone. Up to 15% of adults present with metastatic disease at diagnosis, and as many as 61% of those diagnosed at earlier stages will experience disease recurrence after treatment. Tivdak is composed of Genmab’s human monoclonal antibody directed to tissue factor and Pfizer’s ADC technology. Genmab leads commercialisation of the drug in Europe and all other regions outside the US and China, where Pfizer partners with Genmab and Zai Lab, respectively. The EC’s decision was supported by positive results from the late-stage innovaTV 301 trial, in which Tivdak demonstrated a 30% reduction in risk of death compared to chemotherapy. Median overall was 11.5 months among Tivdak-treated patients and 9.5 months for those randomised to receive chemotherapy. Secondary endpoints of progression-free survival and confirmed objective response rate were also met, with Tivdak reducing the risk of disease progression by 33% compared to chemotherapy. Lead investigator on the innovaTV 301 clinical trial, Ignace Vergote, described the EC approval as “an important step forward in the treatment landscape for advanced cervical cancer”. Vergote said: “Recurrent or metastatic cervical cancer is a devastating disease, and patients can face a difficult treatment journey with limited options. “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.” The approval comes just under a year after the FDA granted full approval for Tivdak in recurrent or metastatic cervical cancer, building on the accelerated approval it gave to the drug in 2021.

ADCE-T02 is a potential first-in-class Topoisomerase I inhibitor-based antibody-drug conjugate (ADC) targeting tissue factor, a validated ADC target overexpressed in multiple solid tumors Phase I Tiffany-01 trial is designed to evaluate the safety, pharmacokinetics, and preliminary efficacy of ADCE-T02 as a monotherapy in patients with advanced solid tumors COPENHAGEN, Denmark, Feb. 26, 2025 /PRNewswire/ -- Adcendo, a biotech company pioneering the development of first and best-in-class ADCs for cancers with a high unmet medical need, today announced that the U.S. Food & Drug Administration (FDA) has provided clearance of the IND application for a Phase I study evaluating ADCE-T02 in patients with advanced solid tumors. Tiffany-01 is an ongoing first-in-human Phase I multicenter, open-label, dose escalation study of ADCE-T02 as a monotherapy in patients with advanced solid tumors. The primary objectives of the study are to determine the maximum tolerated dose and recommended Phase II dose and schedule of ADCE-T02 monotherapy in addition to assessing ADCE-T02 safety and tolerability. The secondary objectives are to characterize the pharmacokinetics and to evaluate the preliminary efficacy of ADCE-T02. The study is currently recruiting in Australia and will start recruiting in the U.S. in the next few months. "Tissue factor (TF) is a validated ADC target with overexpression in many high unmet need solid tumor indications, however, the currently approved TF targeting ADC has severe limitations due to a suboptimal side effect profile and a limited therapeutic window. The highly differentiated profile of ADCE-T02, based on the use of an improved monoclonal antibody and a next generation Topoisomerase I inhibitor linker/payload technology, could overcome those limitations and offer an enhanced therapeutic window and improved side effect profile, which may lead to better clinical outcomes for patients," said Dr. Lone Ottesen, Chief Medical Officer of Adcendo. "The U.S. IND clearance of ADCE-T02 is an important milestone for our program and our company, and we look forward to initiating patient enrollment in the U.S. and working closely with all of our investigators to evaluate the therapeutic utility of this drug in multiple advanced solid tumor indications." Prof. Vinod Ganju. Managing Director of Peninsula and Southeast Oncology (PASO), Melbourne, Australia and Principal Investigator of Tiffany-01, commented: "ADCs have in the past years shown highly encouraging results and have already become Standard of Care in quite a number of solid tumor indications. ADCE-T02 represents an attractive new option to explore in advanced solid tumors with high unmet need. I am pleased to be working with Adcendo to develop ADCE-T02, potentially offering a broader therapeutic window and a better safety profile for our patients." About ADCE-T02 Tissue Factor is a clinically validated ADC target with strong overexpression in multiple tumor indications with high unmet medical need including Cervical Cancer, Head and Neck Cancer, Colorectal Cancer, Non-Small Cell Lung Cancer, and Pancreatic Ductal Adenocarcinoma. ADCE-T02 is a highly differentiated anti-TF ADC, and the first ADC with a Topoisomerase I inhibitor-based linker/payload, clinically developed in Australia and the U.S. Its unique antibody design minimizes the impact on the coagulation pathway, while the T1000-exatecan linker-payload technology platform has been shown to amplify the bystander effect, improve linker stability, and has the potential to overcome emerging resistance mechanisms. These differentiated features are expected to translate into a superior therapeutic window, a better safety profile, enhanced response rates and longer duration of About Adcendo ApS Adcendo ApS is a clinical-stage biotechnology company headquartered in Copenhagen, Denmark, with operations in Boston, Massachusetts. The company is developing a pipeline of first-in-class antibody-drug conjugates (ADCs) targeting cancers with high unmet medical needs. Led by a team of industry veterans with a track record of advancing multiple ADCs to approval, Adcendo integrates novel targets, optimized linker-payload combinations, and a rationally designed development strategy to drive next-generation cancer therapies. For further information, please visit or follow the company on LinkedIn. Logo - WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Improved overall survival (OS), progression-free survival (PFS) and confirmed objective response rate (ORR) were observed in the China subpopulation treated with TIVDAK compared to chemotherapy, consistent with those in the global population The safety profile of TIVDAK among the China subpopulation was manageable and consistent with that observed in the global population Zai Lab intends to submit a New Drug Application (NDA) to China’s National Medical Products Administration (NMPA) in the first quarter of 2025 Zai Lab will leverage its commercial footprint of ZEJULA in women’s cancer to bring the medicine to patients in China if approved SHANGHAI & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan. 15, 2025-- Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) today announced positive topline results from the China subpopulation of the global Phase 3 innovaTV 301 study, demonstrating a clinically meaningful improvement in overall survival with TIVDAK treatment for patients with previously treated recurrent or metastatic cervical cancer compared to chemotherapy. The China subpopulation results were consistent with those in the global population: TIVDAK demonstrated a 45% reduction in the risk of death compared to chemotherapy (HR: 0.55 [95% CI: 0.27-1.15] in the China subpopulation who had received prior standard systemic therapies, with more than half of this Chinese population having received prior anti-PD(L)1 therapy. Median OS for patients treated with TIVDAK was not reached versus chemotherapy 10.7 months [95% CI: 6.0-not reached] with a median follow-up of 11.5 months. Secondary endpoints of PFS and confirmed ORR also favored treatment with TIVDAK compared to chemotherapy. The safety profile of TIVDAK in the China subpopulation was manageable and consistent with the global profile. “Recurrent or metastatic cervical cancer remains a significant challenge for patients, highlighting a critical unmet need for effective treatments that extend survival after relapse,” said Dr. Rafael Amado, M.D., President, Head of Global Research and Development at Zai Lab. “The consistent and positive results in the China subpopulation of the global Phase 3 study reinforce the potential for TIVDAK, the only ADC therapy in this disease setting, to increase options in this therapeutically unmet clinical setting. If approved, we expect TIVDAK to add to ZEJULA and augment our commercial franchise in women’s tumors.” “There are approximately 150,000 new cases of cervical cancer annually in China1, and patients face limited treatment options once their cancer recurs or spreads after initial treatment,” said Dr. Lingying Wu, Professor of the Department of Gynecologic Oncology of National Cancer Center / Cancer Hospital Chinese Academy of Medical Sciences. “While the recent adoption of immunotherapy as a first-line treatment in China represents progress, there is a lack of effective options for patients following relapse. The promising results from TIVDAK, which demonstrated superior survival extension in patients whose disease progressed after initial treatments, including prior anti-PD(L)1 treatment, offer hope for addressing this critical unmet need.” In April 2024, the U.S. Food and Drug Administration (FDA) approved the supplemental Biologics License Application (sBLA) granting full approval for TIVDAK® (tisotumab vedotin-tftv) for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The approval was based on results from the global, randomized, Phase 3 innovaTV 301 clinical trial (NCT04697628), which met its primary endpoint, demonstrating overall survival (OS) benefit in adult patients with previously treated recurrent or metastatic cervical cancer treated with TIVDAK compared to chemotherapy. TIVDAK demonstrated a 30% reduction in the risk of death compared to chemotherapy (hazard ratio [HR]: 0.70 [95% CI: 0.54-0.89], two-sided p=0.0038)2. 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]. PFS and confirmed ORR were also significantly improved compared to chemotherapy. The safety profile of TIVDAK was consistent with its known safety profile as presented in the U.S. prescribing information, and no new safety signals were observed. Based on these encouraging results, Zai Lab intends to submit an NDA for TIVDAK to China’s National Medical Products Administration (NMPA) in the first quarter of 2025. The full China subpopulation data will be presented at a future medical conference in 2025. About innovaTV 301 Trial Design The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase 3 trial evaluating TIVDAK® (tisotumab vedotin) versus investigator’s choice of single agent chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) with recurrent or metastatic cervical cancer who received chemotherapy. 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 Cervical Cancer in China Cervical cancer remains one of the leading causes of cancer death in women in China and globally. An estimated 150,000 new cases of cervical cancer occur annually in China1. Current treatment options are limited for patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy. TIVDAK is well positioned to provide a new option for previously treated advanced cervical cancer patients who currently have limited treatment options and poor outcomes. About TIVDAK® (tisotumab vedotin) TIVDAK® (tisotumab vedotin) 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. TIVDAK received accelerated approval from the FDA in September 2021 and full approval in April 2024 for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Please see full prescribing information, including BOXED WARNING for TIVDAK here. Zai Lab has an exclusive license from Seagen Inc., a company later acquired by Pfizer, to develop and commercialize TIVDAK in Greater China (mainland China, Hong Kong, Macau, and Taiwan, collectively). About Zai Lab Zai Lab (NASDAQ: ZLAB; HKEX: 9688) is an innovative, research-based, commercial-stage biopharmaceutical company based in China and the United States. We are focused on discovering, developing, and commercializing innovative products that address medical conditions with significant unmet needs in the areas of oncology, immunology, neuroscience and infectious disease. Our goal is to leverage our competencies and resources to positively impact human health worldwide. For additional information about Zai Lab, please visit www.zailaboratory.com or follow us at www.twitter.com/ZaiLab_Global. Zai Lab Forward-Looking Statements This press release contains forward-looking statements relating to our future expectations, plans, and prospects, including, without limitation, statements relating to our prospects and plans for developing and commercializing TIVDAK in Greater China, the potential benefits of TIVDAK, and the potential treatment of cervical cancer. These forward-looking statements may contain words such as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “plan,” “possible,” “potential,” “will,” “would,” and other similar expressions. Such statements constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not statements of historical fact or guarantees or assurances of future performance. Forward-looking statements are based on our expectations and assumptions as of the date of this press release and are subject to inherent uncertainties, risks, and changes in circumstances that may differ materially from those contemplated by the forward-looking statements. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including but not limited to (1) our ability to successfully commercialize and generate revenue from our approved products, (2) our ability to obtain funding for our operations and business decisions, (3) the results of our clinical and pre-clinical development of our product candidates, (4) the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approvals of our product candidates, (5) risks related to doing business in China, and (6) other factors identified in our most recent annual and quarterly reports and in other reports we have filed with the U.S. Securities and Exchange Commission. We anticipate that subsequent events and developments will cause our expectations and assumptions to change, and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Our SEC filings can be found on our website at www.zailaboratory.com and the SEC’s website at www.sec.gov. Notes: 1 Bingfeng Han et al., "Cancer incidence and mortality in China, 2022" Journal of the National Cancer Center, 2024. DOI: 10.1016/j.jncc.2024.01.006. 2 The threshold for statistical significance is 0.0226 (2-sided). View source version on businesswire.com: https://www.businesswire.com/news/home/20250115437262/en/ Investor Relations: Christine Chiou / Lina Zhang +1 (917) 886-6929 / +86 136 8257 6943 christine.chiou1@zailaboratory.com / lina.zhang@zailaboratory.com Media: Shaun Maccoun / Xiaoyu Chen +1 (857) 270-8854 / +86 185 0015 5011 shaun.maccoun@zailaboratory.com / xiaoyu.chen@zailaboratory.com Source: Zai Lab Limited