Tisotumab Vedotin Approved in Hong Kong for Recurrent or Metastatic Cervical Cancer

The Hong Kong Department of Health has approved tisotumab vedotin-tftv (Tivdak) for use in adult patients with recurrent or metastatic cervical cancer that has progressed on or following chemotherapy, according to an announcement from Zai Lab Limited.¹

Data from the phase 3 innovaTV 301 trial (NCT04697628) showed that treatment with the antibody-drug conjugate (ADC; n = 253) led to a median overall survival (OS) of 11.5 months (95% CI, 9.8-14.9) vs 9.5 months (95% CI, 7.9-10.7) with chemotherapy (n = 249), translating to a 30% reduction in the risk of death (HR, 0.70; 95% CI, 0.54-0.89; P = .0038).² The median progression-free survival (PFS) in the respective arms was 4.2 months (95% CI, 4.0-4.4) and 2.9 months (95% CI, 2.6-3.1; HR, 0.67; 95% CI, 0.54-0.82; P < .0001). Tisotumab vedotin elicited a confirmed objective response rate (ORR) of 17.8% (95% CI, 13.3%-23.1%) vs 5.2% (95% CI, 2.8%-8.8%) with chemotherapy (P < .0001).

“[The] approval of Tivdak marks an important milestone for Zai Lab, further strengthening our Women’s franchise in Greater China,” Andrew Zhu, chief commercial officer, Greater China at Zai Lab, stated in a news release.¹ “Treatment options for patients with recurrent or metastatic cervical cancer after initial therapy are limited. Tivdak, the first ADC therapy in cervical cancer, delivers a clinically meaningful survival benefit to patients. With our established commercial infrastructure for Zejula in Hong Kong, we are uniquely positioned to ensure Tivdak reaches patients without delay.”

What is the trial design of innovaTV 301 examining tisotumab vedotin, and what patients with cervical cancer were included?

The open-label, active-controlled, multicenter, randomized trial enrolled a total of 502 patients who had recurrent or metastatic cervical cancer.² These patients previously receive 1 or 2 systemic therapy regimens in the recurrent or metastatic setting, which included chemotherapy plus or minus bevacizumab (Avastin) and/or an anti–PD-(L)1 therapy.

Participants were randomized in a 1:1 fashion to receive 2 mg/kg of intravenous tisotumab vedotin every 3 weeks or investigator’s choice of chemotherapy, which could have comprised topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. They were stratified based on prior bevacizumab exposure (yes vs no), prior anti–PD-(L)1 exposure (yes vs no), region (US vs Europe vs other), and ECOG performance status (0 vs 1). Treatment continued until intolerable toxicity or progressive disease. OS served as the trial’s primary end point, and other key end points included PFS and confirmed ORR.

The median patient age was 50 years (range, 26-80) and about half were White (49%) and had an ECOG performance status of 0 (54%). Histologies included squamous cell carcinoma (63%), adenocarcinoma (32%), and adenosquamous (5%). Most patients had extrapelvic disease (90%). With regard to prior treatment, 61% received 1 previous line of systemic therapy and 38% had received 2 prior lines. All had previously received chemotherapy, and more than half (64%) had prior exposure to bevacizumab. Just under one-third (27%) of patients had prior anti–PD-(L)1 therapy. Moreover, most patients on the control arm received gemcitabine (44%), followed by pemetrexed (32%), topotecan (8%), vinorelbine (7%), and irinotecan (6%).

What was learned about the safety profile of tisotumab vedotin ininnovaTV 301?

Thirty-three percent of patients experienced serious adverse effects (AEs) with the ADC. AEs led to dose interruption or reduction for 39% and 30% of patients, respectively; they led to permanent treatment discontinuation for 15% of patients.

The most common all-grade AEs experienced by at least 10% of patients who received tisotumab vedotin (n = 250) vs chemotherapy (n = 239) on the trial included peripheral neuropathy (38%, ADC; 4.2%, chemotherapy), conjunctival adverse reactions (37%; 1.7%), nausea (33%; 40%), fatigue (28%; 32%), epistaxis (26%; 2.5%), constipation (25%; 16%), decreased appetite (24%; 18%), alopecia (24%; 2.9%), diarrhea (22%; 15%), corneal adverse reactions (21%; 0%), dry eye (21%; 1.7%), hemorrhage (21%; 11%), abdominal pain (18%; 15%), vomiting (18%; 18%), pyrexia (17%; 21%), rash (17%; 16%), urinary tract infection (16%; 18%), pruritus (10%; 2.9%), and decreased weight (10%; 5%).

The most common grade 3 or higher AEs in the ADC arm were peripheral neuropathy (6%), fatigue (6%), and urinary tract infection (5%). In the chemotherapy arm, they were urinary tract infection (8%), abdominal pain (2.5%), and hemorrhage (2.5%).

Has tisotumab vedotin been approved for this indication in other countries?

In April 2024, the FDA granted full approval to tisotumab vedotin for this indication based on findings from innovaTV 301.³ In a past interview with OncLive®, Keiichi Fujiwara, MD, PhD, of Saitama Medical University International Medical Center, discussed the significance of the decision for patients with recurrent or metastatic disease.⁴

Subsequently, in March 2025, the Japanese Ministry of Health, Labour, and Welfare also approved the agent for advanced or recurrent cervical cancer that has progressed on or following chemotherapy, signaling the first approval of an ADC for cervical cancer in Japan.⁵ In April 2025, the European Commission also cleared the ADC for use as a monotherapy in this population.⁶

The biologics license application seeking the approval of tisotumab vedotin is currently being reviewed by the National Medical Products Administration of China.¹

References

1. Zai Lab announces approval of Tivdak for patients with recurrent or metastatic cervical cancer in Hong Kong. News release. Zai Lab Limited. September 1, 2025. Accessed September 3, 2025. https://ir.zailaboratory.com/news-releases/news-release-details/zai-lab-announces-approval-tivdakr-patients-recurrent-or
2. Tivdak. Prescribing information. Seagen, Inc; 2024. Accessed September 3, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761208s007lbl.pdf
3. FDA approves tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. FDA. April 29, 2024. Accessed September 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisotumab-vedotin-tftv-recurrent-or-metastatic-cervical-cancer
4. Fujiwara K. Dr Fujiwara on the FDA approval of tisotumab vedotin for recurrent cervical cancer. April 29, 2024. Accessed September 3, 2025. https://www.onclive.com/view/dr-fujiwara-on-the-fda-approval-of-tisotumab-vedotin-for-recurrent-cervical-cancer.
5. 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 September 3, 2025. https://ir.genmab.com/news-releases/news-release-details/tivdakr-tisotumab-vedotin-approved-japan-ministry-health-labour
6. Tivdak (tisotumab vedotin) approved by European Commission for previously treated recurrent or metastatic cervical cancer. News release. Genmab. March 31, 2025. Accessed September 3, 2025. https://ir.genmab.com/news-releases/news-release-details/tivdakr-tisotumab-vedotin-approved-european-commission