On February 2, 2024 Genmab A/S (Nasdaq: GMAB) and Pfizer, Inc. (NYSE PFE) reported that the European Medicines Agency (EMA) has validated for review the marketing authorization application (MAA) of tisotumab vedotin, an antibody-drug conjugate (ADC), developed for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after systemic therapy (Press release, Genmab, FEB 2, 2024, View Source [SID1234639816]). If approved, tisotumab vedotin would be the first ADC granted European Union (EU) marketing authorization for people living with cervical cancer.
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The MAA is based on data from the global, randomized, Phase 3 innovaTV 301 trial (NCT04697628), in which tisotumab vedotin demonstrated superior overall survival (OS), progression-free survival (PFS) and a confirmed objective response rate (ORR) in patients with previously treated recurrent or metastatic cervical cancer compared to chemotherapy. Data from the innovaTV 204 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 MAA. The safety profile of tisotumab vedotin in innovaTV 301 was consistent with its known safety profile as presented in the U.S. prescribing information.
"The validation of our application is an important milestone supporting our commitment to bringing a new therapeutic option for recurring or metastatic cervical cancer to more patients," said Jan van de Winkel, Ph.D., Chief Executive Officer, Genmab. "There continues to be a need for therapeutic options for these patients, and we’re dedicated to delivering potential improved outcomes to women diagnosed with this devastating disease."
"Today’s milestone signifies our progress in exploring the availability of tisotumab vedotin for more patients with recurrent or metastatic cervical cancer," said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. "We remain dedicated to collaborating closely with regulatory authorities, while we navigate the process to potentially deliver a new therapeutic option to people facing this debilitating disease."
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. It is the fourth leading cause of cancer death in women worldwide,i,ii with approximately 570,000 new cases diagnosed and 311,000 new deaths of women annually.iii,iv Recurrent and/or metastatic cervical cancer is a particularly devastating and mostly incurable disease; when diagnosed in later stages, less than 5 percent of these patients survive five years.v In the European Union specifically, cervical cancer ranks 11th among the most frequently occurring cancers in women and 12th among the most frequent causes of cancer death in them.vi
About the innovaTV 301 Trial
The innovaTV 301 trial (NCT04697628) is a global, randomized, open-label Phase 3 trial evaluating tisotumab vedotin 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 chemotherapy doublet +/- bevacizumab and an anti-PD-(L)1 agent (if eligible) are included. The primary endpoint is overall survival. The main secondary outcomes are progression-free survival, confirmed 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, recently acquired by Pfizer, 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). 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 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. Determination of TF expression is not required. 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-tftv (Tivdak) is approved in the U.S. under the accelerated approval program, and a supplemental Biologics License Application (sBLA) seeking to convert its accelerated approval to a full approval was granted Priority Review by the U.S. Food and Drug Administration (FDA). Use of tisotumab vedotin in recurrent or metastatic cervical cancer is not approved in the EU.