TY - JOUR
T1 - Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer
T2 - Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study
AU - Vergote, Ignace
AU - Van Nieuwenhuysen, Els
AU - O'Cearbhaill, Roisin E
AU - Westermann, Anneke
AU - Lorusso, Domenica
AU - Ghamande, Sharad
AU - Collins, Dearbhaile C
AU - Banerjee, Susana
AU - Mathews, Cara A
AU - Gennigens, Christine
AU - Cibula, David
AU - Tewari, Krishnansu S
AU - Madsen, Kristine
AU - Köse, Fatih
AU - Jackson, Amanda L
AU - Boere, Ingrid A
AU - Scambia, Giovanni
AU - Randall, Leslie M
AU - Sadozye, Azmat
AU - Baurain, Jean-François
AU - Gort, Eelke
AU - Zikán, Michal
AU - Denys, Hannelore G
AU - Ottevanger, Nelleke
AU - Forget, Frédéric
AU - Mondrup Andreassen, Camilla
AU - Eaton, Lamar
AU - Chisamore, Michael J
AU - Viana Nicacio, Leonardo
AU - Soumaoro, Ibrahima
AU - Monk, Bradley J
PY - 2023/12/20
Y1 - 2023/12/20
N2 - 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.
AB - 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.
KW - Female
KW - Humans
KW - Bevacizumab/adverse effects
KW - Carboplatin/adverse effects
KW - Uterine Cervical Neoplasms/drug therapy
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Neoplasm Recurrence, Local/etiology
KW - Lung Neoplasms/drug therapy
KW - Anemia/drug therapy
U2 - https://doi.org/10.1200/JCO.23.00720
DO - https://doi.org/10.1200/JCO.23.00720
M3 - Article
C2 - 37651655
SN - 0732-183X
VL - 41
SP - 5536
EP - 5549
JO - Journal of clinical oncology
JF - Journal of clinical oncology
IS - 36
ER -