Tivdak Approved for Cervical Cancer

Tivdak  is the first and only ADC to be granted European Union (EU) marketing authorization for people living with recurrent or metastatic cervical cancer.

The approval is supported by data from the global, randomized, Phase III innovaTV 301 trial (NCT04697628) that evaluated the efficacy and safety of Tivdak  compared to chemotherapy in patients with advanced or recurrent cervical cancer who were previously treated with chemotherapy. The trial met its primary endpoint of overall survival (OS), demonstrating a 30% reduction in risk of death (HR: 0.70 [95% CI: 0.54-0.89], two-sided p=0.0038) compared to chemotherapy. Median OS was 11.5 months [95% CI: 9.8-14.9] among patients treated with Tivdak  compared to 9.5 months [95% CI: 7.9-10.7] for patients who received chemotherapy. Secondary endpoints of progression-free survival (PFS) and confirmed objective response rate (ORR) were also met, further validating its clinical benefit. PFS results were statistically significant, with Tivdak  demonstrating a 33% reduction in the risk of disease progression compared with chemotherapy (HR: 0.67 [95% CI, 0.54-0.82], p<0.0001). Data from the innovaTV 204 (NCT03438396) pivotal Phase II single-arm clinical trial evaluating Tivdak  as monotherapy in patients with previously treated recurrent or metastatic cervical cancer was also included in the marketing authorization application (MAA).   

The most common (≥25%) adverse reactions, including laboratory abnormalities, in patients receiving tisotumab vedotin were peripheral neuropathy (39%), nausea (37%), epistaxis (33%), conjunctivitis (32%), alopecia (31%), anaemia (27%), and diarrhoea (25%).  

The innovaTV 301 trial (NCT04697628) is a global, 1:1 randomized, open-label Phase III  trial evaluating tisotumab vedotin 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. 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.

"We recognize the urgent need to accelerate science and innovate new treatment options for gynecologic cancers, including cervical cancer,” said Brad Bailey, Executive Vice President and Chief Commercial Officer of Genmab. “The European Commission approval of TIVDAK marks a milestone in our work to transform the treatment paradigm and help improve outcomes for patients. As the first medicine that Genmab will bring to patients in Europe independently, we’re committed to bringing this important option to as many patients in Europe with previously treated recurrent or metastatic cervical cancer as possible.”

“Recurrent or metastatic cervical cancer is a devastating disease, and patients can face a difficult treatment journey with limited options,” said  Dr. Ignace Vergote, University Hospitals Leuven, co-founder of European Network of Gynaecological Oncological Trial groups (ENGOT), and lead investigator on the innovaTV 301 clinical trial. “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. This approval is an important step forward in the treatment landscape for advanced cervical cancer.”