Treatment with tisotumab vedotin (Tivdak) has shown a significant improvement in overall survival (OS) compared to chemotherapy in a Chinese subpopulation of patients with previously treated, recurrent or metastatic cervical cancer. These findings come from the phase 3 innovaTV 301 study, and the data are consistent with the global population results, indicating a potential new treatment option for this patient group.
The Chinese subpopulation treated with tisotumab vedotin experienced a 45% reduction in the risk of death compared to those receiving chemotherapy (HR, 0.55; 95% CI, 0.27-1.15). With a median follow-up of 11.5 months, the median OS in the tisotumab vedotin arm was not reached, while it was 10.7 months (95% CI, 6.0-NR) in the chemotherapy arm. This is particularly notable as the patients had previously undergone standard systemic treatment, with over half having prior exposure to anti-PD-(L)1 therapy.
Improved Progression-Free Survival and Response Rate
In addition to the OS benefit, tisotumab vedotin also demonstrated improvements in progression-free survival (PFS) and confirmed objective response rate (ORR) compared to chemotherapy in this subpopulation. The safety profile of tisotumab vedotin was manageable and consistent with previous reports.
Addressing Unmet Needs in China
Lingying Wu, PhD, professor of the Department of Gynecologic Oncology of National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences, noted the significance of these findings: "There are approximately 150,000 new cases of cervical cancer annually in China, and patients face limited treatment options once their cancer recurs or spreads after initial treatment. While the recent adoption of immunotherapy as a first-line treatment in China represents progress, there is a lack of effective options for patients following relapse. The promising results from [tisotumab vedotin], which demonstrated superior survival extension in patients whose disease progressed after initial treatments, including prior anti-PD(L)1 treatment, offer hope for addressing this critical unmet need."
innovaTV 301 Study Details
The randomized, open-label, phase 3 innovaTV 301 study enrolled patients with recurrent or metastatic cervical cancer who had disease progression on or after a chemotherapy doublet with or without bevacizumab and an anti-PD-(L)1 agent, if eligible and available. Patients were required to have received up to 2 prior lines of therapy, have measurable disease by RECIST v1.1 criteria, and an ECOG performance status of 0 or 1. A total of 502 patients were randomized 1:1 to receive either tisotumab vedotin at 2.0 mg/kg intravenously every 3 weeks or investigator’s choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed).
The primary endpoint of the study was OS, with secondary endpoints including PFS, ORR, and safety.
Global Data and Regulatory Approval
Global data from the innovaTV 301 study, presented at the 2023 ESMO Congress, showed a median OS of 11.5 months (95% CI, 9.8-14.9) with tisotumab vedotin vs 9.5 months (95% CI, 7.9-10.7) with chemotherapy (HR, 0.70; 95% CI, 0.54-0.89; log-rank P = .0038). The 12-month OS rates were 48.7% and 35.3%, respectively.
The FDA granted full approval to tisotumab vedotin in April 2024 for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, based on these data. The drug had previously received accelerated approval in September 2021 based on the phase 3 innovaTV 204 study.
Next Steps
Zai Lab Limited plans to submit a new drug application for tisotumab vedotin to the National Medical Products Administration of China in the first quarter of 2025, based on the data from the Chinese subpopulation. Full data from this subpopulation is expected to be presented at a future medical meeting in 2025.
