TY - JOUR
T1 - Tisotumab vedotin in previously treated recurrent or metastatic cervical cancer
AU - Hong, David S.
AU - Concin, Nicole
AU - Vergote, Ignace
AU - de Bono, Johann S.
AU - Slomovitz, Brian M.
AU - Drew, Yvette
AU - Arkenau, Hendrik Tobias
AU - Machiels, Jean Pascal
AU - Spicer, James F.
AU - Jones, Robert
AU - Forster, Martin D.
AU - Cornez, Nathalie
AU - Gennigens, Christine
AU - Johnson, Melissa L.
AU - Thistlethwaite, Fiona C.
AU - Rangwala, Reshma A.
AU - Ghatta, Srinivas
AU - Windfeld, Kristian
AU - Harris, Jeffrey R.
AU - Lassen, Ulrik Niels
AU - Coleman, Robert L.
N1 - Funding Information:
D.S. Hong is a paid consultant for Alpha Insights, Amgen, Axiom, Adaptimmune, Baxter, Bayer, Genentech, GLG, Group H, Guidepoint, Infinity, Janssen, Merrimack, Medscape, Numab, Pfizer, Prime Oncology, Seattle Genetics, Takeda, Trieza Therapeutics, and WebMD; reports receiving commercial research grants from AbbVie, Adaptimmune, Aldi-Norte, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, Fate Therapeutics, Genentech, Genmab, Ignyta, Infinity, Kite, Kyowa, Lilly, LOXO, Merck, Medimmune, Mirati, MiRNA, Molecular Templates, Mologen, Novartis, Pfizer, Seattle Genetics, Takeda, and Turning Point; holds ownership interest (including patents) in Molecular Match, OncoResponse, and Presagia; and reports receiving other remuneration from Genmab, AACR, ASCO, and SITC. I. Vergote is a paid consultant for Roche NV and Genmab. J.S. de Bono reports receiving speakers bureau honoraria from Seattle Genetics and Genmab, and reports receiving other remuneration from AstraZeneca, SanofiAventis, Merck Serono, Bayer, MSD, Pfizer Oncology, Roche/Genentech, Janssen, Astellas, and Daiichi Sankyo. B.M. Slomovitz is a paid consultant for Genmab, GlaxoSmithKline, Clovis, AstraZeneca, and Genentech. Y. Drew reports receiving honoraria for participating in advisory board speakers meeting held at ASCO 2018. H.-T. Arkenau is an employee of HCAHealthcare UK/Sarah Cannon and reports receiving speakers bureau honoraria from Pierre Fabre, Guardant, BeiGene, and Roche. J.-P. Machiels is a paid advisory board member for Pfizer, Roche, AstraZeneca, Bayer, Innate, Merck Serono, Bristol-Myers Squibb, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology, Debio, and Nanbiotix; is an unpaid consultant/advisory board member for MSD; and reports receiving other remuneration from Amgen. R. Jones reports receiving commercial research grants from Merck and reports receiving speakers bureau honoraria from Roche. M.L. Johnson reports receiving commercial research grants from BerGenBio, Lilly, EMD Serono, Mirati Therapeutics, Genmab, Janssen, Pfizer, AstraZeneca, Genentech/Roche, Stemcentrx, Novartis, Checkpoint Therapeutics, Array Bio-pharma, Regeneron, Apexigen, AbbVie, Tarveda, Adaptimmune, Syndax, Neovia, Boehringer Ingelheim, Sanofi, Hengrui Therapeutics, Merck, Daiichi-Sankyo, Lycera, G1 Therapeutics, Dynavax, LOXO, CytomX, BeiGene, Birdie, Corvus, Incyte, Geno-cea, Gritstone, Amgen, Bristol-Myers Squibb, Kadmon, Clovis, Acerta, OncoMed, Guardant Health, Takeda, Shattuck Labs, and GlaxoSmithKline; is an unpaid consultant/advisory board member for Genentech/Roche, Celgene, Boehringer Ingel-heim, Sanofi, Mirati, LOXO, Calithera, AstraZeneca, Merck, Araxes Pharma, Mersana Therapeutics, BeiGene, Incyte, Pfizer, Guardant Health, Bristol-Myers Squibb, and Ribon Therapeutics; and reports receiving other remuneration from AbbVie, Astellas, AstraZeneca, Boehringer Ingelheim, Clovis, Daiichi Sankyo, EMD Serono, Bristol-Myers Squibb, Exelixis, Genentech, Incyte, Merck, Pfizer, Sysmex Inostics, and Vapotherm. F.C. Thistlewaite is a paid consultant for Novartis, GlaxoSmithKline,
Funding Information:
The authors thank the patients and their families and caregivers for participating in this study as well as all site personnel. The authors thank Freddy de Bree at Genmab for his contribution to biomarker data analysis. This study was funded by Genmab A/ S. Tisotumab vedotin is being developed in collaboration with Seattle Genetics, Inc. Medical writing assistance was provided by Emily C. Casey, PhD, of the ApotheCom Genmab Team (San Francisco) and was funded by Genmab A/S.
PY - 2020/3/15
Y1 - 2020/3/15
N2 - Purpose: Tissue factor (TF) is a potential target in cervical cancer, as it is frequently highly expressed and associated with poor prognosis. Tisotumab vedotin, a first-in-class investigational antibody-drug conjugate targeting TF, has demonstrated encouraging activity in solid tumors. Here we report data from the cervical cancer cohort of innovaTV 201 phase I/II study (NCT02001623). Patients and Methods: Patients with recurrent or metastatic cervical cancer received tisotumab vedotin 2.0 mg/kg every 3 weeks until progressive disease, unacceptable toxicity, or consent withdrawal. The primary objective was safety and tolerability. Secondary objectives included antitumor activity. Results: Of the 55 patients, 51% had received ≽2 prior lines of treatment in the recurrent or metastatic setting; 67% had prior bevacizumab þ doublet chemotherapy. Fifty-one percent of patients had squamous cell carcinoma. The most common grade 3/4 treatment-emergent adverse events (AEs) were anemia (11%), fatigue (9%), and vomiting (7%). No grade 5 treatment-related AEs occurred. Investigator-assessed confirmed objective response rate (ORR) was 24% [95% confidence interval (CI): 13%-37%]. Median duration of response (DOR) was 4.2 months (range: 1.0þ -9.7); four patients responded for >8 months. The 6-month progression-free survival (PFS) rate was 29% (95% CI: 17%-43%). Independent review outcomes were comparable, with confirmed ORR of 22% (95% CI: 12%-35%), median DOR of 6.0 months (range: 1.0þ-9.7), and 6-month PFS rate of 40% (95% CI: 24%-55%). Tissue factor expression was confirmed in most patients; no significant association with response was observed. Conclusions: Tisotumab vedotin demonstrated a manageable safety profile and encouraging antitumor activity in patients with previously treated recurrent or metastatic cervical cancer.
AB - Purpose: Tissue factor (TF) is a potential target in cervical cancer, as it is frequently highly expressed and associated with poor prognosis. Tisotumab vedotin, a first-in-class investigational antibody-drug conjugate targeting TF, has demonstrated encouraging activity in solid tumors. Here we report data from the cervical cancer cohort of innovaTV 201 phase I/II study (NCT02001623). Patients and Methods: Patients with recurrent or metastatic cervical cancer received tisotumab vedotin 2.0 mg/kg every 3 weeks until progressive disease, unacceptable toxicity, or consent withdrawal. The primary objective was safety and tolerability. Secondary objectives included antitumor activity. Results: Of the 55 patients, 51% had received ≽2 prior lines of treatment in the recurrent or metastatic setting; 67% had prior bevacizumab þ doublet chemotherapy. Fifty-one percent of patients had squamous cell carcinoma. The most common grade 3/4 treatment-emergent adverse events (AEs) were anemia (11%), fatigue (9%), and vomiting (7%). No grade 5 treatment-related AEs occurred. Investigator-assessed confirmed objective response rate (ORR) was 24% [95% confidence interval (CI): 13%-37%]. Median duration of response (DOR) was 4.2 months (range: 1.0þ -9.7); four patients responded for >8 months. The 6-month progression-free survival (PFS) rate was 29% (95% CI: 17%-43%). Independent review outcomes were comparable, with confirmed ORR of 22% (95% CI: 12%-35%), median DOR of 6.0 months (range: 1.0þ-9.7), and 6-month PFS rate of 40% (95% CI: 24%-55%). Tissue factor expression was confirmed in most patients; no significant association with response was observed. Conclusions: Tisotumab vedotin demonstrated a manageable safety profile and encouraging antitumor activity in patients with previously treated recurrent or metastatic cervical cancer.
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UR - http://www.scopus.com/inward/citedby.url?scp=85081944568&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-19-2962
DO - 10.1158/1078-0432.CCR-19-2962
M3 - Article
C2 - 31796521
AN - SCOPUS:85081944568
VL - 26
SP - 1220
EP - 1228
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 6
ER -