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.
Date
2023-12-20ICR Author
Author
Vergote, I
Van Nieuwenhuysen, E
O'Cearbhaill, RE
Westermann, A
Lorusso, D
Ghamande, S
Collins, DC
Banerjee, S
Mathews, CA
Gennigens, C
Cibula, D
Tewari, KS
Madsen, K
Köse, F
Jackson, AL
Boere, IA
Scambia, G
Randall, LM
Sadozye, A
Baurain, J-F
Gort, E
Zikán, M
Denys, HG
Ottevanger, N
Forget, F
Mondrup Andreassen, C
Eaton, L
Chisamore, MJ
Viana Nicacio, L
Soumaoro, I
Monk, BJ
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Language
eng
Date accepted
2023-07-12
License start date
2023-08-31
Citation
Journal of Clinical Oncology, 2023, pp. JCO2300720 -
Publisher
LIPPINCOTT WILLIAMS & WILKINS