Tisotumab Vedotin in Combination with Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results from the innovaTV 205/GOG-3024/ENGOT-cx8 Study

Ignace Vergote*, Els Van Nieuwenhuysen, Roisin E. O'Cearbhaill, Anneke Westermann, Domenica Lorusso, Sharad Ghamande, Dearbhaile C. Collins, Susana Banerjee, Cara A. Mathews, Christine Gennigens, David Cibula, Krishnansu S. Tewari, Kristine Madsen, Fatih Köse, Amanda L. Jackson, Ingrid A. Boere, Giovanni Scambia, Leslie M. Randall, Azmat Sadozye, Jean François BaurainEelke Gort, Michal Zikán, Hannelore G. Denys, Nelleke Ottevanger, Frédéric Forget, Camilla Mondrup Andreassen, Lamar Eaton, Michael J. Chisamore, Leonardo Viana Nicacio, Ibrahima Soumaoro, Bradley J. Monk

*Corresponding author for this work

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Abstract

PURPOSE Tissue factor is highly expressed in cervical carcinoma and can be targeted by tisotumab vedotin (TV), an antibody-drug conjugate. This phase Ib/II study evaluated TV in combination with bevacizumab, pembrolizumab, or carboplatin for recurrent or metastatic cervical cancer (r/mCC). 

METHODS This open-label, multicenter study (ClinicalTrials.gov identifier: NCT03786081) included dose-escalation arms that assessed dose-limiting toxicities (DLTs) and identified the recommended phase II dose (RP2D) of TV in combination with bevacizumab (arm A), pembrolizumab (arm B), or carboplatin (arm C). The dose-expansion arms evaluated TV antitumor activity and safety at RP2D in combination with carboplatin as first-line (1L) treatment (arm D) or with pembrolizumab as 1L (arm E) or second-/third-line (2L/3L) treatment (arm F). The primary end point of dose expansion was objective response rate (ORR). 

RESULTS A total of 142 patients were enrolled. In dose escalation (n = 41), no DLTs were observed; the RP2D was TV 2 mg/kg plus bevacizumab 15 mg/kg on day 1 once every 3 weeks, pembrolizumab 200 mg on day 1 once every 3 weeks, or carboplatin AUC 5 on day 1 once every 3 weeks. In dose expansion (n = 101), the ORR was 54.5% (n/N, 18/33; 95% CI, 36.4 to 71.9) with 1L TV + carboplatin (arm D), 40.6% (n/N, 13/32; 95% CI, 23.7 to 59.4) with 1L TV + pembrolizumab (arm E), and 35.3% (12/34; 19.7 to 53.5) with 2L/3L TV + pembrolizumab (arm F). The median duration of response was 8.6 months, not reached, and 14.1 months, in arms D, E, and F, respectively. Grade ≥3 adverse events (≥15%) were anemia, diarrhea, nausea, and thrombocytopenia in arm D and anemia in arm F (none ≥15%, arm E).

CONCLUSION TV in combination with bevacizumab, carboplatin, or pembrolizumab demonstrated manageable safety and encouraging antitumor activity in treatment-naive and previously treated r/mCC.

Original languageEnglish
Pages (from-to)5536-5549
Number of pages14
JournalJournal of Clinical Oncology
Volume41
Issue number36
DOIs
Publication statusPublished - 20 Dec 2023

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Publisher Copyright: © American Society of Clinical Oncology.

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