FDA Approves Tisotumab Vedotin for Recurrent/Metastatic Cervical Cancer


Tisotumab vedotin-tftv may now be given to patients with recurrent or metastatic cervical cancer, according to the FDA.

Tisotumabvedotin-tftvmay now be given to patients with recurrent or metastatic cervical cancer, according to the FDA.

Tisotumabvedotin-tftvmay now be given to patients with recurrent or metastatic cervical cancer, according to the FDA.

The FDA has approved tisotumab vedotin-tftv (Tivdak) for patients with recurrent or metastatic cervical cancer that has progressed following prior chemotherapy, according to a press release from the agency.


Support for the approval came from data from the phase 3 innovaTV 301 trial (NCT04697628). These data, which were presented at the 2023 Annual Global Meeting of the International Gynecologic Cancer Society (IGCS), showed a median overall survival (OS) of 11.5 months (95% CI, 9.8-14.9) in patients treated with tisotumab vedotin compared with 9.5 months (95% CI, 7.9-10.7) in patients treated with chemotherapy (HR, 0.70; 95% CI, 0.54-0.89; P = .0038).2 At 12-months, the OS rate was 48.7% vs 35.3% in each respective arm. The median follow-up was 10.8 months (95% CI, 10.3-11.6).


Additionally, the median progression-free survival (PFS) in the tisotumab vedotin and chemotherapy 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), respectively. The 6-month PFS rate in each respective arm was 30.4% vs 18.9%.

Investigators also reported an overall response rate (ORR) of 17.8% (95% CI, 13.3%-23.1%) in the treatment arm and 5.2% (95% CI, 2.8%-8.8%) in the chemotherapy arm. The disease control rate in each respective arm was 75.9% (95% CI, 70.1%-81.0%) compared with 58.2% (95% CI, 51.8%-64.4%).

In this international, open-label trial, a total of 502 patients with recurrent or metastatic cervical cancer were randomly assigned 1:1 to receive either tisotumab vedotin at 2.0 mg/kg intravenously every 3 weeks (n = 253) or investigator’s choice of chemotherapy (n = 249), which included topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed.


Most patients enrolled on in the experimental and chemotherapy arms, respectively, had extra pelvic metastases (89.3% vs 90.4%), 1 prior systemic regimen (62.8% vs 59.8%), previous treatment with bevacizumab (64.8% vs 63.1%), and underwent prior cervical cancer radiotherapy (81.0% vs 81.5%). In patients who had an evaluable biopsy, most (92.4% vs 94.3%) had positive membrane tissue factor expression.

The trial’s primary end point was OS, and the secondary end points were PFS, ORR, time to response, duration of response, and safety. Eligibility for enrollment on the trial included having metastatic or recurrent cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology as well as disease progression on or following prior chemotherapy with or without bevacizumab (Avastin) and an anti–PD-L1 agent.

Most treatment-related adverse effects (TEAEs) reported in patients were low-grade. A total of 87.6% of patients in the experimental arm and 85.4% of patients in the chemotherapy arm reported any grade TEAEs, with 29.2% and 45.2% in each arm reporting a high-grade TEAE. AEs of special interest included ocular and peripheral neuropathy and bleeding events, and the most common any-grade TEAEs included anemia (12.8% vs 43.9%) and neutropenia (6.4% vs 21.8%).


Prior to the full approval, tisotumab vedotin received accelerated approval from the FDA in September 2021.3 The agency then granted priority review to a supplemental biologics license application in January 2024.4 



  1. FDA approves tisotumab vedotin-tftv for recurrent or metastatic cervical cancer. News release. FDA. April 29, 2024. Accessed April 29, 2024. https://tinyurl.com/ets4ma4b
  2. Slomovitz BM, Martin AG, Fujiwara K, et al. innovaTV 301/ENGOT-cx12/GOG-3057: a global, randomized, open-label, phase 3 study of tisotumab vedotin vs investigator's choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer. Presented at 2023 Annual Global Meeting of the International Gynecologic Cancer Society; November 5-7, 2023; Seoul, Korea; abstract SE006/1616
  3. Seagen and Genmab announce FDA accelerated approval for TIVDAK™ (tisotumab vedotin-tftv) in previously treated recurrent or metastatic cervical cancer. News release. Seagen Inc. and Genmab A/S. September 20, 2021. Accessed January 9, 2024. https://bwnews.pr/2XJLowv
  4. TIVDAK® supplemental biologics license application accepted for priority review by FDA for patients with recurrent or metastatic cervical cancer. News release. Pfizer Inc. January 9, 2024. Accessed January 9, 2024. https://rb.gy/8b2e8l
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