Tisotumab Vedotin in Recurrent or Metastatic Cervical Cancer

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In a phase II study (innovaTV 204/GOG-3023/ENGOT-cx6) reported in The Lancet Oncology, Robert L. Coleman, MD, and colleagues found that the tissue factor–directed antibody-drug conjugate tisotumab vedotin produced durable responses in previously treated patients with recurrent or metastatic cervical cancer.

Robert L. Coleman, MD

Robert L. Coleman, MD

Study Details

In the trial, 101 patients with measurable disease from sites in Europe and the United States were enrolled between June 2018 and April 2019. Patients had recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer; disease progression on or after doublet chemotherapy with bevacizumab (if eligible by local standards); and had received two or fewer previous systemic regimens for recurrent or metastatic disease. Treatment consisted of tisotumab vedotin given intravenously at 2.0 mg/kg (up to a maximum of 200 mg) once every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate on Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by an independent review committee.


Median follow-up at the time of analysis was 10.0 months (interquartile range = 6.1–13.0 months).

Objective response was observed in 24 patients (24%, 95% confidence interval [CI] = 16%–33%), including complete response in 7 (7%). An additional 49 patients (49%) had stable disease, yielding a disease control rate of 72%. Median duration of response was 8.3 months (95% CI = 4.2 months–not reached), with 62% of responders having an ongoing response at ≥ 6 months. Median time to response was 1.4 months. Responses were observed irrespective of membrane tissue factor expression level.

Median progression-free survival was 4.2 months, with a 6-month rate of 30%; median overall survival was 12.1 months, with 6- and 12-month rates of 79% and 51%.


  • Objective response was observed in 24% of patients.
  • Median response duration was 8.3 months, with 62% of responders having an ongoing response at ≥ 6 months.

Adverse Events

The most common treatment-related adverse events of any grade included alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%).

Grade ≥ 3 treatment-related adverse events were reported in 28% of patients, with the most common being neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2% each with sensory, motor, sensorimotor, and neuropathy-peripheral). Serious treatment-related adverse events occurred in 13% of patients, with the most common being peripheral sensorimotor neuropathy (2%) and pyrexia (2%). Treatment was discontinued due to adverse events in 12% of patients. One death, due to septic shock, was considered to be related to treatment.

The investigators concluded, “Tisotumab vedotin showed clinically meaningful and durable antitumor activity with a manageable and tolerable safety profile in women with previously treated recurrent or metastatic cervical cancer. Given the poor prognosis for this patient population and the low activity of current therapies in this setting, tisotumab vedotin, if approved, would represent a new treatment for women with recurrent or metastatic cervical cancer.”

Dr. Coleman, of US Oncology Research, The Woodlands, TX, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Genmab, Seagen, Gynaecologic Oncology Group, and European Network of Gynaecological Oncological Trial Groups. For full disclosures of the study authors, visit

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