4621 - A Phase IIa study of tisotumab vedotin in patients with previously treated recurrent or metastatic cervical cancer: updated analysis of full cervical expansion cohort

Background

Treatment options for recurrent or metastatic cervical cancer are limited, with no standard of care beyond 1L treatment and 2L response rates of ∼13%. Tisotumab vedotin (TV) is an antibody-drug conjugate comprised of a fully human monoclonal antibody specific for tissue factor (TF) conjugated to the microtubule disrupting-agent monomethyl auristatin E (MMAE) via a protease cleavable linker. TV is being evaluated in GEN701 (innovaTV 201), a Phase I/IIa dose-escalation and expansion study in patients (pts) with previously treated recurrent locally advanced or metastatic solid tumours. A previous report of the preliminary expansion cohort for cervical cancer (n = 34) showed an investigator (INV)-assessed response rate of 32% (26% confirmed) (Vergote et al., ESMO 2017 abstract #931O). INV response for the full cervical expansion cohort (N = 55) and response by independent imaging review (IIR) (n = 34) are presented here.

Methods

Key eligibility criteria included recurrent or metastatic cervical cancer that progressed on standard therapy, adequate organ function and ECOG 0-1. TV 2 mg/kg Q3W was given until progression, toxicity or withdrawal. Activity and safety were assessed by RECIST 1.1 and CTCAE 4.03, respectively. Enrollment started in November 2015 and continued through May 2018.

Results

The full cohort has 55 pts (median age was 47 y [21-74]). Updated efficacy by INV review, safety data, and response by TF expression will be presented. Median age in the first 34 pts was 44 y (21-74) and pts received a median of 2 prior lines for recurrent or metastatic disease. ORR by IIR of 41% (95% CI: 25%-59%), including 1 CR and 13 PR. 8 (1 CR, 7 PRs) were confirmed (24%; 95% CI: 11%-41%). Confirmed response rate was concordant between INV and IIR (26% and 24%). Median duration of response was 4.9 months and median PFS was 4.2 months by IIR.

Conclusions

These data demonstrate that TV has encouraging activity in previously treated recurrent or metastatic cervical cancer, an underserved population with a high unmet need, and that responses observed with TV are numerically higher than those achieved by historical controls. These data support the continued investigation of TV in this population.

Clinical trial identification

NCT02001623.

Legal entity responsible for the study

Genmab A/S and Seattle Genetics, Inc.

Funding

Genmab A/S and Seattle Genetics, Inc.

Editorial Acknowledgement

Medical writing and editorial support provided by Ogilvy CommonHealth, during the development of this abstract, under the guidance of the primary author Dr. Nicole Concin, and funded by Genmab A/S and Seattle Genetics, Inc.

Disclosure

I.B. Vergote: Consulting/Advisory board: Roche NV, Genmab A/S, Advaxis Inc, Morphotek Inc, F. Hoffmann-La Roche Ltd, Cerulean Pharma Inc, Novocure GMBH, AstraZeneca, Mateon Therapeutics Inc, Immunogen Inc, Eli Lilly Benelux NV, Amgen Inc, Theradex Europe Limited, Pfizer Inc, Debiopharma International SA, Vifor Pharma Belgi€e NV, Novartis Pharma AG, MSD Belgium BVBA, Janssen-Cilag, Bayer Pharma AG, Clovis Oncology, Takeda, PharmaMar, Oncoinvent; Contracted research: Morphotek; Grants/corporate sponsored research: Amgen, Roche; Accommodations/travel expenses: Tesaro, Clovis Oncology, Takeda, PharmaMar, Roche, Genmab, Oncoinvent. M.L. Johnson: Research funding: BerGenBio, Lilly, EMD Serono, Janssen, Mirati Therapeutics, Genmab, Pfizer, AstraZeneca, Genentech/Roche, Stemcentrix, Novartis, Checkpoint Therapeutics, Array BioPharma, Regeneron, Apexigen, Abbvie, Tarveda, Adaptimmune, Syndax, Neovia, Boehringer Ingelheim, Sanofi, Hengrui Therapeutics, INC, Merck, Daiichi-Sankyo, Lycera, G1 Therapeutics, Dynavax; Consulting/advisory: Genentech/Roche, Celgene, Boehringer Ingelheim, Sanofi, Mirati, LOXO; Contract lobbyist: Astellas, Otsuka Pharmaceuticals. R.L. Coleman: Grant funding and Scientific Steering Committee roles: Janssen, AstraZeneca, Clovis, Merck, Abbvie, Gamamab, Genmab, Samumed, Roche/Genentech. K. Windfeld: Employee of Genmab; Stock ownership Genmab. S. Ghatta, R.A. Rangwala: Employee of Genmab. D.S. Hong: Research/Grant funding: Adapitmmune, Abbvie, Amgen, AstraZeneca, Bayer, BMS, Daiichi-Sanko, Eisai, Genentech, Genmab, Ignyta, Infinity, Kite Kyowa, Lilly, LOXO, Mirati, Merck, Medimmune, Molecular Template, Novartis, Pfizer, Takeda; Travel, Accommodations, Expenses: Loxo, MiRNA; Consulting or Advisory role: Baxter, Bayer, Guidepoint Global, Janssen; Other ownership interests: Molecular Match (Advisor), Oncoresponse (founder). All other authors have declared no conflicts of interest.