Tisotumab Vedotin Gains Japanese Approval for Advanced Cervical Cancer

Tisotumab Vedotin in Cervical Cancer

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The Japanese Ministry of Health, Labour and Welfare has approved tisotumab vedotin-tftv (Tivdak) for the treatment of patients with advanced or recurrent cervical cancer that has progressed on or after chemotherapy.1 This marks the first approval of an antibody-drug conjugate (ADC) for the treatment of patients with cervical cancer in Japan.

The approval is supported by results from the global, randomized, open-label phase 3 innovaTV 301 trial (NCT04697628), which evaluated the efficacy and safety of tisotumab vedotin compared with standard chemotherapy in patients previously treated for advanced or recurrent cervical cancer. The study enrolled 502 patients, including 101 from Japan, and met its primary end point of overall survival (OS).

Treatment with tisotumab vedotin demonstrated a 30% reduction in the risk of death compared with chemotherapy (HR, 0.70; 95% CI, 0.54-0.89; two-sided P = .0038). Median OS was 11.5 months (95% CI, 9.8-14.9) in the tisotumab vedotin arm vs 9.5 months (95% CI, 7.9-10.7) in the chemotherapy arm.

Secondary end points of progression-free survival (PFS) and confirmed objective response rate (ORR) were also achieved, demonstrating a median PFS of 4.2 months (95% CI, 4.0-4.4) with tisotumab vedotin compared with 2.9 months (95% CI, 2.6-3.1) for chemotherapy (HR, 0.67; 95% CI, 0.54-0.82; P < .001).2 The confirmed ORR was 17.8% with tisotumab vedotin vs 5.2% with chemotherapy (OR, 4.0; 95% CI, 2.1-7.6; P < .001).

Adverse effects (AEs) were reported in 87.6% of patients (n = 219/250), including 50 Japanese patients.1 The most common AEs (≥20%) included conjunctivitis (30.4%), nausea (29.2%), peripheral sensory neuropathy (26.8%), alopecia (24.4%), and epistaxis (22.8%).

“Patients with advanced or recurrent cervical cancer, in general, have a poor prognosis. The advent of new treatment options, especially for second-line or later treatment, is much needed,” Aikou Okamoto, MD, PhD, chief professor, Department of Obstetrics and Gynecology at The Jikei University School of Medicine, stated in a news release. “Cervical cancer treatment has advanced in recent years, but it is very meaningful that the approval of tisotumab vedotin as an ADC has increased the number of treatment options with a new mechanism of action that is expected to prolong OS. This is good news for patients and health care professionals,” Okamoto added.

InnovaTV 301 Trial Design and Patient Population

The innovaTV 301 trial is a global, randomized, open-label phase 3 study designed to evaluate the efficacy and safety of tisotumab vedotin compared with investigator’s choice of chemotherapy in patients with recurrent or metastatic cervical cancer. A total of 502 patients were enrolled and randomized in a 1:1 ratio to receive either tisotumab vedotin monotherapy or one of five single-agent chemotherapy options selected by the investigator: topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.

Eligible patients included those with squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix, and evidence of disease progression following one or two prior systemic regimens in the recurrent or metastatic setting.3 Prior therapies could include a platinum-based chemotherapy doublet with or without bevacizumab (Avastin), and an anti–PD-L1 agent if clinically indicated.2

Patients in the experimental arm received tisotumab vedotin at a dose of 2.0 mg/kg administered intravenously (IV) once every 3 weeks.3 In the control arm, patients received their assigned chemotherapy per standard dosing schedules: topotecan IV on days 1 to 5 every 21 days, vinorelbine IV on days 1 and 8 every 21 days, gemcitabine IV on days 1 and 8 every 21 days, irinotecan IV weekly for 28 days every 42 days, or pemetrexed IV on day 1 every 21 days.

The primary end point of the trial was OS, defined as the time from randomization to death from any cause. In the absence of confirmed death, OS was censored at the last date the patient was known to be alive, with a maximum follow-up period of 25 months. Secondary end points included PFS and confirmed ORR.

“As a company, we understand the urgent need for patients with advanced cervical cancer whose disease has progressed,” Judith Klimovsky, MD, executive vice president and chief development officer of Genmab, added in a news release.1 “This approval marks an important step forward in transforming the treatment paradigm in Japan, ultimately bringing new hope and possibility to patients and their loved ones,” she concluded.

References

1. TIVDAK (tisotumab vedotin) approved by Japan Ministry of Health, Labour and Welfare for the treatment of advanced or recurrent cervical cancer that has progressed on or after chemotherapy. News release. March 27, 2025. Accessed March 27, 2025. https://ir.genmab.com/news-releases/news-release-details/tivdakr-tisotumab-vedotin-approved-japan-ministry-health-labour
2. Ignace V, González-Martín A, Fujiwara K, et al. Tisotumab vedotin as second- or third-line therapy for recurrent cervical cancer. N Engl J Med. 2024;391(1):44-55. doi:10.1056/NEJMoa2313811
3. Tisotumab vedotin vs chemotherapy in recurrent or metastatic cervical cancer (innovaTV 301). ClinicalTrials.gov. Updated March 25, 2025. Accessed March 27, 2025. https://clinicaltrials.gov/study/NCT04697628