Despite HPV vaccination and preventive screening programs, recurrent or metastatic cervical cancer is still diagnosed. Historically, these patients were treated with chemotherapy and bevacizumab. The addition of pembrolizumab demonstrated a major improvement in overall survival and became the new standard of care. Nevertheless, there remains a need for additional treatment options, particularly given the poor prognosis associated with recurrent disease.
In cervical cancer, as in many other solid tumors, tumor cells express Tissue Factor (TF). Tisotumab vedotin (TV) is an antibody-drug conjugate (ADC) targeting TF that induces direct cytotoxicity, a bystander effect, antibody-dependent cellular cytotoxicity, phagocytosis, and immunogenic cell death. In the United States, TV monotherapy has already been approved based on the significant improvements in objective response rate and duration of response observed in the BGOG-cx6 study.
This study included several treatment arms in which TV was administered every three weeks in combination with bevacizumab, pembrolizumab, or carboplatin.
The safety profile of the different combinations was acceptable and consistent with expectations based on the known safety data of the individual agents. Combining TV with bevacizumab carried a potential risk of overlapping toxicities, but no major differences were observed in this group. Consequently, the selected dose of TV in the combination regimens was identical to that used in monotherapy.
This study demonstrated that TV has promising antitumor activity when combined with bevacizumab, pembrolizumab, or carboplatin, without altering the safety profile. These findings support further investigation of these combinations in patients with recurrent or metastatic cervical cancer. The data have led to the opening of an additional study arm evaluating TV in combination with carboplatin and pembrolizumab, with or without bevacizumab.