BLA Accepted in China for Tisotumab Vedotin in Recurrent/Metastatic Cervical Cancer

China’s National Medical Products Administration has accepted for review a biologics license application (BLA) seeking the approval of tisotumab vedotin-tftv (Tivdak) for the treatment of patients with recurrent or metastatic cervical cancer who have disease progression on or after systemic therapy.1

The BLA is supported by data from the phase 3 innovaTV 301 trial (NCT04697628) and the findings from the China subpopulation analysis of the trial. Findings reported in January 2025 showed that the results of the China subpopulation analysis were consistent with those seen in the global population. At a median follow-up of 11.5 months, the median overall survival (OS) was not reached (NR) among patients in the China subpopulation previously treated with standard systemic therapies who received tisotumab vedotin vs 10.7 months (95% CI, 6.0-NR) in those who received chemotherapy, translating to a 45% reduction in the risk of death with the antibody-drug conjugate (ADC; HR, 0.55; 95% CI, 0.27-1.15).1,2 Notably, over half of patients in the China subpopulation had received prior PD-1/PD-L1–directed therapy.

The progression-free survival (PFS) and overall response rate (ORR) were also improved in the tisotumab vedotin arm vs the chemotherapy arm. Additionally, the safety profile of the ADC in the China subpopulation was reported to be manageable and consistent with that of the global population.

“In China, cervical cancer is a serious health concern with approximately 150,000 new cases diagnosed annually,” Rafael Amado, MD, president and head of Global Research and Development at Zai Lab, stated in a news release.1 “Treatment options for patients experiencing recurrence or metastasis after initial treatment are limited. [Tisotumab vedotin], the only ADC therapy in cervical cancer, demonstrated promising benefits including a clinically meaningful improvement in OS in the pivotal global innovaTV 301 trial. If approved, [tisotumab vedotin] will leverage our existing commercial infrastructure for [niraparib (Zejula)], expanding our ability to offer treatment for women’s cancer.”

The global, open-label, randomized innovaTV 301 trial is investigating tisotumab vedotin vs investigator’s choice of single-agent chemotherapy (gemcitabine, irinotecan, pemetrexed, topotecan, or vinorelbine) in patients with recurrent or metastatic cervical cancer, including those with squamous cell, adenocarcinoma, or adenosquamous disease histology.3 Patients were required to have disease progression during or after treatment with a chemotherapy doublet with or without bevacizumab (Avastin) and a PD-1/PD-L1–directed agent. Patients also needed to have received 1 or 2 prior systemic therapies for recurrent and/or metastatic cervical cancer; measurable disease per RECIST 1.1 criteria; an ECOG performance status of 0 or 1; and a life expectancy of at least 3 months.

Tisotumab vedotin was administered at 2.0 mg/kg every 3 weeks, which became the FDA-recommended dose of the agent.3,4

OS served as the primary end point.3 Key secondary end points included PFS, ORR, time to response, duration of response, safety, and quality of life.

Notably, in April 2024, the FDA granted full approval to tisotumab vedotin for the treatment of adult patients with recurrent or metastatic cervical cancer who have disease progression on or after chemotherapy.4 This regulatory decision was supported by global findings from innovaTV 301.

In the global population, tisotumab vedotin generated a 30% reduction in the risk of death vs chemotherapy (HR, 0.70; 95% CI, 0.54-0.89; 2-sided P = .0038). The median OS in the tisotumab vedotin and chemotherapy arms was 11.5 months (95% CI, 9.8-14.9) vs 9.5 months (95% CI, 7.9-10.7), respectively. Furthermore, the median PFS was 4.2 months (95% CI, 4.0-4.4) vs 2.9 months (95% CI, 2.6-3.1) in these respective populations (HR, 0.67; 95% CI, 0.54-0.82; P <.0001). The confirmed ORR was 17.8% (95% CI, 13.3%-23.1%) with tisotumab vedotin vs 5.2% (95% CI, 2.8%-8.8%) with chemotherapy (P < .0001).

References

1. Zai Lab announces acceptance of biologics license application for Tivdak for the treatment of patients with recurrent or metastatic cervical cancer. News release. Zai Lab Limited. March 12, 2025. Accessed March 13, 2025. https://ir.zailaboratory.com/news-releases/news-release-details/zai-lab-announces-acceptance-biologics-license-application
2. Zai Lab announces positive topline results for Tivdak in the China subpopulation of the global phase 3 innovaTV 301 trial in patients with recurrent or metastatic cervical cancer. News release. Zai Lab Limited. January 15, 2025. Accessed March 13, 2025. https://ir.zailaboratory.com/news-releases/news-release-details/zai-lab-announces-positive-topline-results-tivdak-china
3. Tisotumab vedotin vs chemotherapy in recurrent or metastatic cervical cancer (innovaTV 301). ClinicalTrials.gov. Updated March 12, 2025. Accessed March 13, 2025. https://clinicaltrials.gov/study/NCT04697628
4. FDA approves tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. FDA. April 29, 2024. Accessed March 13, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisotumab-vedotin-tftv-recurrent-or-metastatic-cervical-cancer