Zai Lab Reports Positive TIVDAK Results in China for Cervical Cancer
Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) has announced positive topline results from the China subpopulation of the global Phase 3 innovaTV 301 study, demonstrating that TIVDAK (tisotumab vedotin) significantly improves overall survival for patients with recurrent or metastatic cervical cancer who have previously been treated with standard systemic therapies, including anti-PD(L)1 treatment. These results mirror those seen in the global population of the study.
Zai Lab In the China subpopulation, TIVDAK reduced the risk of death by 45% compared to chemotherapy (Hazard Ratio: 0.55 [95% CI: 0.27-1.15]). The median overall survival (OS) for patients treated with TIVDAK was not reached, while chemotherapy treatment resulted in a median OS of 10.7 months (95% CI: 6.0-not reached), with a median follow-up of 11.5 months. Secondary endpoints, including progression-free survival (PFS) and objective response rate (ORR), also favored TIVDAK over chemotherapy.
The safety profile of TIVDAK in this subpopulation was manageable and aligned with the results from the global cohort. Dr. Rafael Amado, President and Head of Global Research and Development at Zai Lab, noted that recurrent or metastatic cervical cancer represents a significant challenge for patients, and there is a critical need for treatments that can extend survival after relapse. He emphasized that the promising results from the China subpopulation of the Phase 3 study reinforce TIVDAK’s potential as a novel therapy, the only antibody-drug conjugate (ADC) in this disease setting. If approved, TIVDAK could become an important addition to Zai Lab’s portfolio, alongside ZEJULA, further enhancing their commercial presence in women’s oncology.
Cervical cancer remains a significant health issue in China, with approximately 150,000 new cases reported annually. For patients whose cancer recurs or spreads after initial treatment, effective treatment options are severely limited. While immunotherapy has been recently adopted as a first-line treatment in China, patients who relapse still face a lack of effective options. Dr. Lingying Wu, a prominent expert in gynecologic oncology at the National Cancer Center / Cancer Hospital Chinese Academy of Medical Sciences, highlighted that the positive results from TIVDAK offer hope for addressing this unmet need, particularly for patients who have already received prior treatments, including anti-PD(L)1 therapies.
In April 2024, TIVDAK received full approval from the U.S. Food and Drug Administration (FDA) through a supplemental Biologics License Application (sBLA) for the treatment of recurrent or metastatic cervical cancer in patients whose disease has progressed after chemotherapy.
This approval was based on the results from the global Phase 3 innovaTV 301 study, which demonstrated a 30% reduction in the risk of death for patients treated with TIVDAK compared to chemotherapy (Hazard Ratio: 0.70 [95% CI: 0.54-0.89], p=0.0038). In the global trial, the median OS for TIVDAK patients was 11.5 months (95% CI: 9.8-14.9) compared to 9.5 months (95% CI: 7.9-10.7) for those receiving chemotherapy. Both PFS and ORR were also significantly improved in the TIVDAK group. The safety profile observed Zai Lab in this trial was consistent with its known profile, with no new safety signals.
Zai Lab plans to submit a New Drug Application (NDA) for TIVDAK to the National Medical Products Administration (NMPA) in China in the first quarter of 2025. The full data from the Zai Lab China subpopulation of the study will be presented at a future medical conference in 2025.
The Phase 3 innovaTV 301 trial (NCT04697628) is a global, randomized, open-label study evaluating TIVDAK versus investigator’s choice of chemotherapy in patients with recurrent or metastatic cervical cancer. The trial included patients with squamous cell carcinoma, adenocarcinoma, or adenosquamous histology whose disease had progressed during or after chemotherapy, with or without prior anti-PD-(L)1 treatment.Zai Lab The primary endpoint of the study was overall survival, and key secondary endpoints included 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, the European Network of Gynecological Oncological Trial Groups (ENGOT), and the Gynecologic Oncology Group (GOG) Foundation, among other global cooperative groups.
Cervical cancer continues to be one of the leading causes of cancer-related deaths among women in China and worldwide. With about 150,000 new cases reported annually in China, the disease remains a significant health burden. Current treatment options for patients with recurrent or metastatic cervical cancer are limited, particularly for those who have failed prior therapies. TIVDAK is poised to provide a new treatment option for these patients, potentially improving survival outcomes in a population with few therapeutic alternatives.
TIVDAK is an antibody-drug conjugate (ADC) that targets tissue factor (TF), which is expressed in various cancer cells, including cervical cancer cells. By linking a potent chemotherapy agent, monomethyl auristatin E (MMAE), to a monoclonal antibody targeting TF, TIVDAK can deliver targeted therapy directly to cancer cells, disrupting their microtubules and leading to cell death.
Zai Lab holds an exclusive license from Seagen (now part of Pfizer) to develop and commercialize TIVDAK in Greater China, including mainland China, Hong Kong, Macau, and Taiwan. The company is focused on developing innovative therapies to address unmet medical needs in oncology and other therapeutic areas.
