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.
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.
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.
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
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.