Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Journal of clinical oncology, 2023-12, Vol.41 (36), p.5536-5549

Ort / Verlag

United States

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

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