Treatment of recurrent or metastatic cervical cancer with tisotumab vedotin had durable antitumor activity that was clinically meaningful and well-tolerated with a manageable safety profile, according to the results of a study published in The Lancet Oncology.

The study authors reported that “…tisotumab vedotin has the potential to change the treatment landscape for this disease regardless of [tissue factor] expression, histology, or previous treatment with doublet chemotherapy plus bevacizumab.”

Tisotumab vedotin is an investigational antibody-drug conjugate directed against tissue factor (TF), a protein commonly found in cervical cancer and many other solid tumors. Tisotumab vedotin binds to TF on target cells and induces cell cycle arrest and apoptotic cell death.

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The innovaTV 204 phase 2 multicenter trial ( Identifier: NCT03438396) was conducted across 35 academic centers, hospitals, and community practices in Europe and the United States with the aim of evaluating the efficacy and safety of tisotumab vedotin in women with previously treated recurrent or metastatic cervical cancer. The study included patients aged 18 years or older who had recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer; disease progression on first-line treatment; previously received 2 or fewer systemic regimens for recurrent or metastatic disease; measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1; and an Eastern Cooperative Oncology Group performance status of 0 or 1.

Patients received 2.0 mg/kg (up to a maximum of 200 mg) tisotumab vedotin intravenously every 3 weeks until disease progression as determined by the independent review committee (IRC), or unacceptable toxicity. The primary endpoint was confirmed objective response rate based on RECIST version 1.1, as assessed by the IRC. Secondary endpoints included duration of response, time to response, and progression-free survival (PFS).

Antitumor activity and safety analyses were performed in 101 patients who received at least one dose of tisotumab vedotin during a median follow-up of 10.0 months (interquartile range 6.1-13·0). Treatment with tisotumab vedotin had an objective response rate of 24% (95% CI, 16-33) that included 7% complete responses, 17% partial responses, and a median duration of response of 8.3 months. The median PFS was 4.2 months, and overall survival was 12.1 months. Tumors responded rapidly to tisotumab vedotin, with a median time to response of 1.4 months. The majority of patients (79%) showed reductions in the target lesion size from baseline after treatment with tisotumab vedotin and a 72% disease control rate.

Treatment-emergent adverse events (TEAEs) with tisotumab vedotin were mild to moderate and could be resolved. The most common TEAEs were alopecia (38%), epistaxis (30%), nausea (27%), conjunctivitis (26%), fatigue (26%), and dry eye (23%). Grade 3 or worse TEAEs that occurred in 28% of the study participants were neutropenia (3%), fatigue (2%), ulcerative keratitis (2%), and peripheral neuropathies (2%). Of the serious TEAEs (13%), the most common included peripheral sensorimotor neuropathy (2%) and pyrexia (2%). One death from septic shock was treatment-related and 3 deaths were unrelated to treatment.

 “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,” the authors concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original article for a full list of authors’ affiliations.


Coleman R, Lorusso D, Gennigens C, et al. Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021;22(5):609-619. doi:10.1016/ S1470-2045(21)00056-5