BOTHELL - Seagen Inc. (Nasdaq: SGEN) and Genmab A/S (Nasdaq: GMAB) announced today that the Phase 3 innovaTV 301 global trial in recurrent or metastatic cervical cancer patients with disease progression on or after front-line therapy who received TIVDAK (tisotumab vedotin-tftv), compared with chemotherapy alone, met its primary endpoint of overall survival (OS).
An Independent Data Monitoring Committee determined that OS crossed the pre-specified efficacy boundary at interim analysis. The key secondary endpoints of investigator-assessed progression-free survival and objective response rate also demonstrated statistical significance. The safety profile of TIVDAK in innovaTV 301 was consistent with the known safety profile of TIVDAK as presented in the U.S. prescribing information, and no new safety signals were observed.
The results of innovaTV 301/ENGOT cx-12/GOG 3057, a global, randomized, open-label Phase 3 trial, add to the previous results of innovaTV 204, which served as the basis for the accelerated approval of TIVDAK in the U.S. Subject to discussions with regulatory authorities, the results from innovaTV 301 are intended to serve as the pivotal confirmatory trial for the U.S. accelerated approval and support global regulatory applications. The innovaTV 301 China extension study has been initiated and continues to enroll patients, in collaboration with Zai Lab Limited.
'TIVDAK is the only U.S. Food and Drug Administration-approved therapy in second-line recurrent or metastatic cervical cancer regardless of biomarker status, tumor histology and prior therapy,' said Roger Dansey, M.D., President of Research and Development and Chief Medical Officer at Seagen. 'Demonstrating a survival benefit with the results of innovaTV 301 is a critical milestone in our efforts to ensure more adults living with advanced cervical cancer have an approved treatment option.'
'With limited options for advanced cervical cancer patients who have progressed after front-line therapy, there is a need for therapeutic options with new mechanisms of action, particularly those with a demonstrated survival benefit,' said Jan van de Winkel, Ph.D., Chief Executive Officer, Genmab. 'These results provide hope for patients with recurrent or metastatic cervical cancer.'
Results of the Phase 3 innovaTV 301 clinical trial will be submitted for presentation at an upcoming medical congress and discussed with regulatory authorities.
About Cervical Cancer
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 16% of adults are diagnosed with metastatic disease at diagnosis1,2 and, for adults diagnosed at earlier stages who receive treatment, up to 61% will experience disease recurrence and progress to metastatic cervical cancer.3 It is estimated that in 2023, more than 13,960 new cases of invasive cervical cancer will be diagnosed in the U.S. and 4,310 adults will die from the disease.4
About the innovaTV 301 Trial
The innovaTV 301 trial (NCT04697628) is a global, randomized, open-label Phase 3 trial evaluating TIVDAK (tisotumab vedotin-tftv) versus investigator's choice of chemotherapy alone (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed) in 502 patients with recurrent or metastatic cervical cancer who received no more than 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 a standard of care systemic chemotherapy doublet or platinum-based therapy (if eligible) are included. The main efficacy outcome measure is overall survival. The main secondary outcomes are progression-free survival, objective response rate, time to response, and duration of response, as assessed by the investigator, as well as safety and quality of life outcomes.
The study was conducted by Seagen 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).
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 Seagen's ADC technology that utilizes a protease-cleavable linker that covalently attaches the microtubule-disrupting agent monomethyl auristatin E (MMAE) to the antibody. Determination of TF expression is not required. Nonclinical data suggest that the anticancer activity of TIVDAK 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, TIVDAK also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.
In September 2021, the U.S. Food and Drug Administration granted accelerated approval for TIVDAK in adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. TIVDAK is the first and only approved ADC for the treatment of these patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. The Phase 3 innovaTV 301 clinical trial, an open-label, randomized, global trial, is intended as the confirmatory trial for use in verifying and describing the clinical benefit and for global regulatory applications.
About Seagen
Founded 25 years ago, Seagen Inc. is a global biotechnology company that discovers, develops, manufactures and commercializes targeted cancer therapeutics, with antibody-drug conjugates (ADCs) at our core. Our colleagues work together with urgency to improve and extend the lives of people living with cancer. An ADC technology trailblazer, approximately one-third of FDA-approved and marketed ADCs use Seagen technology. Seagen is headquartered in Bothell, Washington and has locations in California, Canada, Switzerland and across Europe.
About 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 more than 20 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational research and data sciences, which has resulted in a proprietary pipeline including bispecific T-cell engagers, next-generation immune checkpoint modulators, effector function enhanced antibodies and antibody-drug conjugates. 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.
Established in 1999, Genmab is headquartered in Copenhagen, Denmark with locations in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan.
About the Seagen and Genmab Collaboration
Tisotumab vedotin is being co-developed by Genmab and Seagen, under an agreement in which the companies share costs and profits for the product on a 50:50 basis.
Seagen Forward Looking Statements
Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential for results from the innovaTV 301 clinical trial to serve as the confirmatory trial for the U.S. accelerated approval and support global regulatory applications; plans to share the results at an upcoming medical congress and discuss them with regulatory authorities; the conduct of the ongoing innovaTV 301 trial and the therapeutic potential of TIVDAK, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the possibility that results from the innovaTV 301 trial may not be sufficient to support the conversion of the U.S. accelerated approval of TIVDAK to full approval or any global regulatory approvals; that adverse events or safety signals may occur; that adverse regulatory actions may occur; the possibility of delays, setbacks or failures in clinical development activities, the submission of regulatory applications and the regulatory review process for a variety of reasons, including the inherent difficulty and uncertainty of pharmaceutical product development; the inability to provide information and institute safety mitigation measures as may be required by the FDA or other regulatory authorities from time to time and failure to properly conduct or manage clinical trials.
Genmab Forward Looking Statements
This Company Announcement contains forward looking statements. The words 'believe', 'expect', 'anticipate', 'intend' and 'plan' and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab's most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab's most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov . Genmab does not undertake any obligation to update or revise forward looking statements in this Company Announcement nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.
Contact:
David Caouette
Tel: (310) 430-3476
Email: dcaouette@seagen.com
SEAGEN INC. 
