931O - A Phase IIa Study of Tisotumab Vedotin (HuMax®-TF-ADC) in Patients With Relapsed, Recurrent and/or Metastatic Cervical Cancer

Date 08 September 2017
Event ESMO 2017 Congress
Session Gynaecological cancers
Topics Anti-Cancer Agents & Biologic Therapy
Drug Development
Cervical Cancer
Gynaecologic Malignancies
Presenter Ignace Vergote
Citation Annals of Oncology (2017) 28 (suppl_5): v330-v354. 10.1093/annonc/mdx372
Authors I. Vergote1, E. Dean2, U. Lassen3, J. de Bono4, Y. Drew5, J. Machiels6, D. Nielsen7, H. Arkenau8, M. Forster9, R. Jones10, B. Slomovitz11, J. Spicer12, M. Johnson13, N. Cornez14, C. Gennigens15, B. Fulton16, S. Lisby17, L. Basse18, R. Coleman19, D.S. Hong20
  • 1Gynaecologie-verloskunde, University Hospital Leuven, 3000 - Leuven/BE
  • 2Clinical Trials Unit, The Christie NHS Foundation Trust, M20 4BX - Manchester/GB
  • 3Dept. Of Oncology, Phase 1 Unit, Rigshospitalet, 2100   - Copenhagen/DK
  • 4Section Of Medicine, Institute of Cancer Research Royal Marsden Hospital, SM2 5PT - Sutton/GB
  • 5Freeman Hospital, Newcastle General Hospital Northern Centre for Cancer Treatment, NE4 6BE - Newcastle upon Tyne/GB
  • 6Oncology, Roi Albert II, 1200 - Brussels/BE
  • 7Department Of Oncology, Herlev and Gentofte Hospital, 2730 - Herlev/DK
  • 8Oncology, Sarah Cannon Research Institute SCRI UK, W1G 6AD - London/GB
  • 9Oncology, University College London Cancer Institute, WC1E6BT - London/GB
  • 10Oncology, Velindre Cancer Centre Velindre Hospital, CF14 2TL - Cardiff/GB
  • 11Miller School Of Medicine, University of Miami, 33146 - Miami/US
  • 12Oncology, King's College London Guy's Hospital, SE1 9RT - London/GB
  • 13Oncology, Sarah Cannon Research Institute, 37203 - Nashville/US
  • 14Oncology, Centre Hospitalier Universitaire et Psychiatrique de Mons-Borinage, 7000 - Mons/BE
  • 15Oncology, Centre Hospitalier Uuniversitaire Sart Tilman, 4000 - Liège/BE
  • 16Oncology, Beatson West of Scotland Cancer Centre, 1000 - Glasgow/GB
  • 17Medical Department, Genmab A/S, Copenhagen/DK
  • 18Medical Department, Genmab, 1260 - Copenhagen/DK
  • 19Oncology, MD Anderson Cancer Center, 77030-3721 - Houston/US
  • 20Phase I Unit, The University of Texas M. D. Anderson Cancer Center, 77035 - Houston/US

Abstract

Background

There are limited therapeutic options available for patients (pts) with relapsed, recurrent, and/or metastatic cervical cancer. Historic data indicate dismal outcome with ORR of 0-15% and a median OS of 6-8 months (Mo). Tisotumab vedotin (Tv) is an antibody-drug conjugate (ADC) composed of a Tissue Factor specific human IgG1 monoclonal antibody conjugated to a microtubule disrupting agent Monomethyl Auristatin E (MMAE) and is being tested in an ongoing Ph I/IIa dose-escalation study (NCT02001623) in pts with locally advanced and/or metastatic solid tumors. Here, we present initial data on the pre-planned 30 pt expansion cohort in relapsed, recurrent, or metastatic cervical cancer.

Methods

Key eligibility criteria included recurrent or metastatic cervical cancer with at least 1 prior line of therapy, adequate liver and kidney function and ECOG 0-1. Tv was given as 2 mg/kg q3w until progression. Efficacy and toxicity were assessed according to RECIST 1.1 and CTCAE 4.03.

Results

Thirty pts were enrolled. Median age was 43 (21-73), median prior lines 2 (1-5). Twenty-nine pts had previously received cisplatin, 28 a taxane and 19 also bevacizumab. Preliminary efficacy data for 19 pts were available at time of submission. Ten pts (33%) experienced Gr 3 TEAE(s) related to GI (2 pts), anemia (2 pts), infections (1 pt), neuropathy (1 pt), bleeding (1 pt), other (7 pts). No Gr 4 or 5 AEs were reported. The toxicity profile appeared to be consistent with MMAE-based ADCs, including peripheral neuropathy and neutropenia with an identified compound-specific toxicity of conjunctivitis for which prophylactic management was introduced. Seven of the 19 pts (37%) evaluable for efficacy obtained a clinical response; hereof, 6 were confirmed at time of submission. With a mean follow-up of 5.5 Mo for the 7 responders, 5 remain on trial with none of the responders having relapsed. Full efficacy data for all 30 pts will be available at time of presentation.

Conclusions

Preliminary data demonstrated a manageable safety profile and encouraging efficacy (ORR 37%) in relapsed, recurrent or metastatic cervical cancer. Our findings in a high unmet medical need population warrant further investigation.

Clinical trial identification

NCT02001623, released November 14, 2013

Legal entity responsible for the study

Genmab A/S

Funding

Genmab A/S

Disclosure

E. Dean: Employee of The Christie NHS Foundation Trust and The University of Manchester during this research but currently employed by AstraZeneca. The Christie NHS Foundation Trust received institutional commercial income for the conduct of the research. J. de Bono: Employed by The institute of Cancer Research, have served on Genmab Advisory Board, have served as advisor on advisory boards for multiple industry partners incl. AstraZeneca, Daiichi-Sankyo, Genentech, GSK, Merck, Pfizer, Sanofi, Taiho a.o. M. Johnson: Lilly Serono Kadmon Janssen Mirati Therapeutics Genmab Pfizer AstraZeneca Genentech/Roche Novartis Checkpoint Therapeutics Array BioPharma Regeneron Abbvie Merrimack Tarveda Astellas, Otsuka, Genentech/Roche, Boehringer-Ingelheim. S. Lisby, L. Basse: Employed by Genmab and hold shares in the company. R. Coleman: Member of Genmab\'s Advisory Board for Tisotumab vedotin. D.S. Hong: Research/Grant Funding: Bayer, Lilly, Genentech, LOXO, Pfizer, Amgen, Mirati, Ignyta, Merck, Daichi-Sanko, Eisai; Travel, Accommodations, Expenses: MiRNA, LOXO; Consulting Role: Bayer, Baxter, Guidepoint Global Other: Oncoreseponse (founder). All other authors have declared no conflicts of interest.