A review of the novel tissue factor antibody–drug conjugate: Tisotumab vedotin

Abstract

Objective To review and compare the pharmacology, efficacy, and safety of the novel tissue factor antibody–drug conjugate, tisotumab vedotin Data sources Literature search was performed through PubMed MEDLINE, Google Scholar, ClinicalTrials.gov, and the Food and Drug Administration. Data summary Tisotumab vedotin, a novel tissue factor antibody–drug conjugate, was granted accelerated approval by the US FDA on 20 September 2021 for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. Tisotumab vedotin demonstrated clinical efficacy in a number of solid tumors in innovaTV 201 and more specifically in cervical cancer in the pivotal phase 2 innovaTV 204. In the single-arm innovaTV 204 study, 101 patients with recurrent or metastatic cervical cancer received intravenous tisotumab vedotin at the recommended dose of 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The independent review committee confirmed an objective response rate of 24% with 7% complete responses and 17% partial responses. Tisotumab vedotin is associated with several notable adverse events with data from innovaTV 204 including ocular toxicity, hemorrhage, and peripheral neuropathy. Ninety-two percent of patients experienced treatment-related adverse events with 28% experiencing an adverse event of grade 3 or higher. Conclusions Metastatic cervical cancer has a high risk of relapse with few effective second-line therapeutic options. Current guidelines recommend single agent tisotumab vedotin as a possible option. Ongoing trials will further define its place in therapy.

Therapeutic Potential of Tisotumab Vedotin in the Treatment of Recurrent or Metastatic Cervical Cancer: A Short Report on the Emerging Data

“…These results encouraged the continuation of the clinical research of TV in the treatment of TF-expressing solid tumours. 26 …”

“…14,28 Moreover, the frequency of ocular events, including conjunctivitis, was further reduced after the implementation of mitigation measures. 26 The interim analysis of the phase I/II InnovaTV 205 study showed promising activity when TV was used in combination with platinum and pembrolizumab with manageable and non overlapping toxicity profiles 31,32 ORR was 54.5%, 40.6% and 38.3% in patients treated with first line TV + carboplatin, first line TV + pembrolizumab and second/ third line TV + pembrolizumab, respectively. 31 In the last year, the results of KEYNOTE-826 changed the paradigm of first line treatment of advanced/recurrent cervical cancer and pembrolizumab has been approved for patients with CPS ≥ 1 in combination with carboplatinpaclitaxel ± bevacizumab for advanced or recurrent, chemo-naïve, cervical cancer patients.…”

“… 14 , 28 Moreover, the frequency of ocular events, including conjunctivitis, was further reduced after the implementation of mitigation measures. 26 …”

“…14 These results encouraged the continuation of the clinical research of TV in the treatment of TF-expressing solid tumours. 26 ENGOT-cx6/GOG-3023/innovaTV 204 is an open-label, multicentre, single-arm, phase-2 trial 27 (NCT03438396) which enrolled 101 patients with recurrent or advanced cervical cancer (squamous cell, adenocarcinoma, or adenosquamous histology) who had a disease progressing after platinum based chemotherapy plus or minus bevacizumab, and had received no more than 2 previous systemic regimens for recurrent or metastatic disease. 28 The primary endpoint of the study was confirmed ORR by RECIST (version 1.1).…”