- Validation is supported by data from Phase 3 innovaTV 301 trial
COPENHAGEN, Denmark I February 02, 2024 IGenmab A/S (Nasdaq: GMAB) and Pfizer, Inc. (NYSE PFE) today announced 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. If approved, tisotumab vedotin would be the first ADC granted European Union (EU) marketing authorization for people living with cervical cancer.
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.
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.
TIVDAK® (tisotumab vedotin tftv) U.S. USES AND IMPORTANT SAFETY INFORMATION
Use
TIVDAK is indicated in the U.S. for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Please see full prescribing information, including BOXED WARNING for TIVDAK here.
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. For more information, please visit Genmab.com and follow us on Twitter.com/Genmab.
About Pfizer Oncology
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, bispecifics and other immunotherapies. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer and hematologic malignancies, as well as melanoma, gastrointestinal, gynecological and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to extend and improve patients’ lives. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X (Twitter) at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
About the Pfizer and Genmab Collaboration
Tisotumab vedotin is being co-developed by Genmab and Pfizer, under an agreement in which the companies share costs and profits for the product on a 50:50 basis.
| i Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492. |
| ii Torre LA, Islami F, Siegel RL, Ward EM, Jemal A. Global Cancer in women: burden and trends. Cancer Epidemiol Biomark Prev. 2017;26(4):444–57. https://doi.org/10.1158/1055-9965.EPI-16-0858. |
| iii Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020;8(2):e191–203. https://doi.org/10.1016/S2214-109X(19)30482-6. |
| iv Arbyn M, Castellsagué X, de Sanjosé S, Bruni L, Saraiya M, Bray F, et al. Worldwide burden of cervical cancer in 2008. Ann Oncol. 2011;22(12):2675–86. https://doi.org/10.1093/annonc/mdr015. |
| v Waggoner SE. Cervical cancer. Lancet. 2003;361(9376):2217–2225 |
| vi “Cervical Cancer Burden in EU-27 – Europa.Eu.” Cancer Factsheets in EU-27 Countries, ECIS – European Cancer Information System, 17 Nov. 2021, ecis.jrc.ec.europa.eu/pdf/factsheets/cervical_cancer_en-Nov_2021.pdf. |
SOURCE: Genmab
Post Views: 140
- Validation is supported by data from Phase 3 innovaTV 301 trial
COPENHAGEN, Denmark I February 02, 2024 IGenmab A/S (Nasdaq: GMAB) and Pfizer, Inc. (NYSE PFE) today announced 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. If approved, tisotumab vedotin would be the first ADC granted European Union (EU) marketing authorization for people living with cervical cancer.
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.
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.
TIVDAK® (tisotumab vedotin tftv) U.S. USES AND IMPORTANT SAFETY INFORMATION
Use
TIVDAK is indicated in the U.S. for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Please see full prescribing information, including BOXED WARNING for TIVDAK here.
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. For more information, please visit Genmab.com and follow us on Twitter.com/Genmab.
About Pfizer Oncology
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, bispecifics and other immunotherapies. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer and hematologic malignancies, as well as melanoma, gastrointestinal, gynecological and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to extend and improve patients’ lives. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X (Twitter) at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
About the Pfizer and Genmab Collaboration
Tisotumab vedotin is being co-developed by Genmab and Pfizer, under an agreement in which the companies share costs and profits for the product on a 50:50 basis.
| i Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492. |
| ii Torre LA, Islami F, Siegel RL, Ward EM, Jemal A. Global Cancer in women: burden and trends. Cancer Epidemiol Biomark Prev. 2017;26(4):444–57. https://doi.org/10.1158/1055-9965.EPI-16-0858. |
| iii Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020;8(2):e191–203. https://doi.org/10.1016/S2214-109X(19)30482-6. |
| iv Arbyn M, Castellsagué X, de Sanjosé S, Bruni L, Saraiya M, Bray F, et al. Worldwide burden of cervical cancer in 2008. Ann Oncol. 2011;22(12):2675–86. https://doi.org/10.1093/annonc/mdr015. |
| v Waggoner SE. Cervical cancer. Lancet. 2003;361(9376):2217–2225 |
| vi “Cervical Cancer Burden in EU-27 – Europa.Eu.” Cancer Factsheets in EU-27 Countries, ECIS – European Cancer Information System, 17 Nov. 2021, ecis.jrc.ec.europa.eu/pdf/factsheets/cervical_cancer_en-Nov_2021.pdf. |
SOURCE: Genmab
Post Views: 140
