Tisotumab Vedotin Improves Survival in Cervical Cancer Subpopulation

"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," according to Lingying Wu, PhD, of the National Cancer Center / Cancer Hospital Chinese Academy of Medical Sciences.

Treatment with tisotumab vedotin-tftv (Tivdak) yielded a clinically meaningful overall survival (OS) improvement vs chemotherapy among patients with previously treated metastatic or recurrent cervical cancer, according to a press release on China subpopulation findings from the phase 3 innovaTV 301 trial (NCT04697628).¹

In the China subpopulation of the study, tisotumab vedotin reduced the risk of death by 45% vs chemotherapy (HR, 0.55; 95% CI, 0.27-1.15). After a median follow-up of 11.5 months, the median OS was not reached (NR) in the tisotumab vedotin arm and 10.7 months (95% CI, 6.0-NR) in the chemotherapy arm.

Outcomes related to the secondary end points of progression-free survival (PFS) and confirmed objective response rate (ORR) also appeared to improve with tisotumab vedotin vs chemotherapy. Additionally, the safety profile of tisotumab vedotin in the China subpopulation was manageable and comparable with prior reports from the global population.

Developers plan to submit a new drug application (NDA) to China’s National Medical Products Administration (NMPA) in the first quarter of 2025 based on findings from the China subpopulation of the trial. Investigators anticipate presenting full data from this subpopulation at a future medical meeting in 2025.

“There are approximately 150,000 new cases of cervical cancer annually in China, and patients [have] 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,” Lingying Wu, PhD, a professor in the Department of Gynecologic Oncology at the National Cancer Center / Cancer Hospital Chinese Academy of Medical Sciences, stated in the press release.¹ “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.”

In the international, open-label innovaTV 301 trial, 502 patients with recurrent or metastatic cervical cancer were randomly assigned 1:1 to receive tisotumab vedotin at 2.0 mg/kg every 3 weeks or investigator’s choice of chemotherapy.² Treatment options in the comparator arm included topotecan (Hycamtin), vinorelbine, gemcitabine, irinotecan, or pemetrexed.

The trial’s primary end point was OS. Secondary end points included PFS, ORR, time to response, duration of response, and treatment-emergent adverse effects.

Patients 18 years and older with recurrent or metastatic cervical cancer of squamous cell, adenocarcinoma, or adenosquamous histology and progressive disease on or after treatment with a standard-of-care systemic chemotherapy doublet or platinum-based regimen were eligible for enrollment on the trial. Other requirements for study entry included having received 1 or 2 prior lines of systemic therapy for recurrent and/or metastatic cervical cancer, measurable disease per RECIST v1.1 guidelines, an ECOG performance status of 0 or 1, and a life expectancy of at least 3 months.

The FDA previously approved tisotumab vedotin for patients with metastatic or recurrent cervical cancer following disease progression on chemotherapy in April 2024.³ The regulatory agency based its decision on findings from the innovaTV 301 trial.

“Recurrent or metastatic cervical cancer remains a significant challenge for patients, highlighting a critical unmet need for effective treatments that extend survival after relapse. The consistent and positive results in the China subpopulation of the global phase 3 study reinforce the potential for [tisotumab vedotin], the only [antibody drug conjugate] therapy in this disease setting, to increase options in this therapeutically unmet clinical setting,” Rafael Amado, MD, president and head of Global Research and Development at Zai Lab, concluded.¹

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 16, 2025. https://tinyurl.com/y2yyvjew
2. Tisotumab vedotin vs chemotherapy in recurrent or metastatic cervical cancer (innovaTV 301). ClinicalTrials.gov. Updated August 9, 2024. Accessed January 16, 2025. https://tinyurl.com/2s8a82xz
3. FDA approves tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. News release. FDA. April 29, 2024. Accessed January 16, 2025. https://tinyurl.com/ets4ma4b