PMID- 31796521
OWN - NLM
STAT- MEDLINE
DCOM- 20210114
LR  - 20240210
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 26
IP  - 6
DP  - 2020 Mar 15
TI  - Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer.
PG  - 1220-1228
LID - 10.1158/1078-0432.CCR-19-2962 [doi]
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 + 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: 1.0(+)-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: 1.0(+)-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.
CI  - (c)2019 American Association for Cancer Research.
FAU - Hong, David S
AU  - Hong DS
AUID- ORCID: 0000-0001-8721-1609
AD  - Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, 
      The University of Texas MD Anderson Cancer Center, Houston, Texas. 
      dshong@mdanderson.org.
FAU - Concin, Nicole
AU  - Concin N
AD  - Oncology, University Hospitals Leuven, Leuven, Belgium.
FAU - Vergote, Ignace
AU  - Vergote I
AUID- ORCID: 0000-0002-7589-8981
AD  - Oncology, University Hospitals Leuven, Leuven, Belgium.
FAU - de Bono, Johann S
AU  - de Bono JS
AD  - Division of Clinical Studies, The Institute of Cancer Research and Royal Marsden 
      NHS Foundation Trust, London, United Kingdom.
FAU - Slomovitz, Brian M
AU  - Slomovitz BM
AD  - Gynecologic Oncology, Sylvester Comprehensive Cancer Center, University of Miami, 
      Miami, Florida.
FAU - Drew, Yvette
AU  - Drew Y
AUID- ORCID: 0000-0001-6676-9224
AD  - Medical Oncology, Northern Centre for Cancer Care, The Newcastle-upon-Tyne 
      Hospitals NHS Foundation Trust and Northern Institute for Cancer Research, 
      Newcastle University, Newcastle-upon-Tyne, United Kingdom.
FAU - Arkenau, Hendrik-Tobias
AU  - Arkenau HT
AD  - Oncology, Sarah Cannon Research Institute, London, United Kingdom.
FAU - Machiels, Jean-Pascal
AU  - Machiels JP
AD  - Service d'Oncologie Medicale, Institut Roi Albert II, Cliniques Universitaires 
      Saint-Luc and Institut de Recherche Clinique et Experimentale, UCLouvain, 
      Brussels, Belgium.
FAU - Spicer, James F
AU  - Spicer JF
AD  - Comprehensive Cancer Centre, King's College London, Guy's Hospital, London, 
      United Kingdom.
FAU - Jones, Robert
AU  - Jones R
AD  - Biosciences, Cardiff University and Velindre NHS Trust, Cardiff, United Kingdom.
FAU - Forster, Martin D
AU  - Forster MD
AD  - Department of Oncology, University College London Cancer Institute, University 
      College London Hospitals, London, United Kingdom.
FAU - Cornez, Nathalie
AU  - Cornez N
AD  - Oncology, Centre Hospitalier Universitaire Ambroise Pare, Mons, Belgium.
FAU - Gennigens, Christine
AU  - Gennigens C
AD  - Department of Medical Oncology, Centre Hospitalier Universitaire de Liege, Liege, 
      Belgium.
FAU - Johnson, Melissa L
AU  - Johnson ML
AD  - Medical Oncology, Sarah Cannon Research Institute, Nashville, Tennessee.
FAU - Thistlethwaite, Fiona C
AU  - Thistlethwaite FC
AD  - Medical Oncology, The Christie NHS Foundation Trust, The University of 
      Manchester, Manchester, United Kingdom.
FAU - Rangwala, Reshma A
AU  - Rangwala RA
AD  - Medical, Genmab US, Inc., Princeton, New Jersey.
FAU - Ghatta, Srinivas
AU  - Ghatta S
AD  - Clinical Science, Genmab US, Inc., Princeton, New Jersey.
FAU - Windfeld, Kristian
AU  - Windfeld K
AD  - Biostatistics, Genmab, Copenhagen, Denmark.
FAU - Harris, Jeffrey R
AU  - Harris JR
AD  - Translational Research, Genmab US, Inc., Princeton, New Jersey.
FAU - Lassen, Ulrik Niels
AU  - Lassen UN
AD  - Clinical Oncology, Rigshospitalet, Copenhagen, Denmark.
FAU - Coleman, Robert L
AU  - Coleman RL
AUID- ORCID: 0000-0001-9343-8754
AD  - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer 
      Center, Houston, Texas.
LA  - eng
SI  - ClinicalTrials.gov/NCT02001623
GR  - 18887/CRUK_/Cancer Research UK/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20191203
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (Immunoconjugates)
RN  - 0 (Oligopeptides)
RN  - T41737F88A (tisotumab vedotin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*therapeutic use
MH  - Antineoplastic Agents, Immunological/*therapeutic use
MH  - Carcinoma, Squamous Cell/*drug therapy/secondary
MH  - *Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Immunoconjugates/therapeutic use
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Neoplasm Recurrence, Local/*drug therapy/pathology
MH  - Oligopeptides/*therapeutic use
MH  - Patient Safety
MH  - Progression-Free Survival
MH  - Treatment Outcome
MH  - Uterine Cervical Neoplasms/*drug therapy/pathology
MH  - Young Adult
EDAT- 2019/12/05 06:00
MHDA- 2021/01/15 06:00
CRDT- 2019/12/05 06:00
PHST- 2019/09/10 00:00 [received]
PHST- 2019/11/05 00:00 [revised]
PHST- 2019/11/26 00:00 [accepted]
PHST- 2019/12/05 06:00 [pubmed]
PHST- 2021/01/15 06:00 [medline]
PHST- 2019/12/05 06:00 [entrez]
AID - 1078-0432.CCR-19-2962 [pii]
AID - 10.1158/1078-0432.CCR-19-2962 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2020 Mar 15;26(6):1220-1228. doi: 10.1158/1078-0432.CCR-19-2962. 
      Epub 2019 Dec 3.