Tisotumab Vedotin Boosts Survival in Chinese Subpopulation With Previously Treated Cervical Cancer

Treatment with tisotumab vedotin-tftv (Tivdak) led to improved overall survival (OS) compared with chemotherapy in a Chinese subpopulation of patients with previously treated, recurrent or metastatic cervical cancer enrolled in the phase 3 innovaTV 301 study (NCT04697628).1

Data from the subpopulation proved to be consistent with what had been reported with the antibody-drug conjugate (ADC) in the global population. Tisotumab vedotin led to a 45% reduction in the risk of death vs chemotherapy (HR, 0.55; 95% CI, 0.27-1.15). At a median follow-up of 11.5 months, the median OS with the ADC was not yet reached (NR) vs 10.7 months (95% CI, 6.0-NR) with chemotherapy. Notably, this population had previously received standard systemic treatment, and more than half had prior exposure to an anti–PD-(L)1 therapy.

The ADC also led to improved progression-free survival (PFS) and confirmed objective response rate (ORR) vs chemotherapy in this subpopulation. Moreover, the safety profile of tisotumab vedotin proved manageable and consistent with what had been previously reported.

“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,” Lingying Wu, PhD, professor of the Department of Gynecologic Oncology of National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences, stated in a news release. “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.”

The randomized, open-label, phase 3 innovaTV 301 study enrolled patients with recurrent or metastatic cervical cancer who experienced disease progression on or following a chemotherapy doublet with or without bevacizumab (Avastin) and an anti–PD-(L)1 agent if eligible and available.2 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.

They (n = 502) were randomly assigned 1:1 to receive the ADC at a dose of 2.0 mg/kg intravenously every 3 weeks (n = 253) or investigator’s choice of chemotherapy (n = 249) in the form of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. Stratification factors included performance status (0 vs 1), prior receipt of bevacizumab (yes vs no), prior exposure to a PD-L1 or PD-1 agent (yes vs no), and geographic region (United States, Europe, or other). The primary end point of the study was OS, and important secondary end points included PFS, ORR, and safety.

Data from the global population were shared during the 2023 ESMO Congress. In that population, the median OS with tisotumab vedotin was 11.5 months (95% CI, 9.8-14.9) 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 with the ADC or chemotherapy were 48.7% and 35.3%, respectively.

Moreover, the median PFS with tisotumab vedotin was 4.2 months (95% CI, 4.0-4.4) vs 2.9 months (95% CI, 2.6-3.1) with chemotherapy (HR, 0.67; 95% CI, 0.54-0.82; log-rank P < .0001); the respective 6-month PFS rates were 30.4% and 18.9%. The ADC elicited an ORR of 17.8% (95% CI, 13.3%-23.1%) vs 5.2% (95% CI, 2.8%-8.8%) with chemotherapy (OR, 4.0; 95% CI, 2.1-7.6; P < .0001).

These data supported the FDA’s decision to grant a full approval to tisotumab vedotin for use in patients with recurrent or metastatic cervical cancer with disease progression or or after chemotherapy in April 2024.3 The ADC previously received accelerated approval from the regulatory agency in September 2021 for this indication based on findings from the phase 3 innovaTV 204 study (NCT03438396).4 Here, tisotumab vedotin elicited an ORR of 24% (95% CI, 15.9%-33.3%) by independent review committee assessment and RECIST v1.1 criteria.5

Prior safety data from innovaTV 301 showed that the most common treatment-related toxicities reported with tisotumab vedotin included conjunctivitis (30.4%), nausea (29.2%), peripheral sensory neuropathy (26.8%), alopecia (24.4%), epistaxis (22.8%), reduced appetite (18.0%), diarrhea (16.0%), keratitis (15.6%), anemia (12.8%), and neutropenia (6.4%).2

Based on the data reported in the Chinese subpopulation, Zai Lab Limited shared intentions to submit a new drug application for tisotumab vedotin to the National Medical Products Administration of China in the first quarter of this year.1 They also noted that the full data in this population is slated for presentation at a future medical meeting in 2025.

References

1. 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 January 15, 2025. https://ir.zailaboratory.com/news-releases/news-release-details/zai-lab-announces-positive-topline-results-tivdak-china
2. Vergote IB, Martin AG, Fujiwara K, et al. innovaTV 301/ENGOT-cx12/GOG-3057: a global, randomized, open-label, phase III study of tisotumab vedotin vs investigator’s choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer. Ann Oncol. 2024;34(suppl 2):S1276-S1277. doi:10.1016/j.annonc.2023.10.029
3. FDA approves tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. FDA. April 29, 2024. Accessed January 15, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisotumab-vedotin-tftv-recurrent-or-metastatic-cervical-cancer
4. Genmab and Seagen announce FDA accelerated approval for Tivdak (tisotumab vedotin-tftv) in previously treated recurrent or metastatic cervical cancer. News release. Genmab A/S and Seagen Inc. September 20, 2021. Accessed January 15, 2025. https://ir.genmab.com/news-releases/news-release-details/genmab-and-seagen-announce-fda-accelerated-approval-tivdaktm
5. Coleman RL, Lorusso D, Gennigens C, et al. Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer: results from the phase 2 innovaTV 204/GOG-3023/ENGOT-cx6 study. Ann Oncol. 2020;31(suppl 4):S1162-S1163. doi:10.1016/j.annonc.2020.08.2262