LBA9 - innovaTV 301/ENGOT-cx12/GOG-3057: A global, randomized, open-label, phase III study of tisotumab vedotin vs investigator’s choice of chemotherapy in 2L or 3L recurrent or metastatic cervical cancer

Background

Tisotumab vedotin (TV) is an investigational antibody-drug conjugate composed of a tissue factor-directed human monoclonal antibody covalently linked to cytotoxic MMAE. In the US, TV monotherapy received accelerated approval for the treatment of adult pts with recurrent or metastatic cervical cancer (r/mCC) with disease progression on or after chemotherapy. Here, innovaTV 301 (NCT04697628) study results of TV vs investigator’s choice of chemotherapy in pts with r/mCC following 1L therapy are presented.

Methods

Eligible pts had r/mCC with disease progression on/after treatment with standard of care chemotherapy doublet ± bevacizumab ± anti-PD-(L)1 therapy, measurable disease per RECIST v1.1, and ECOG PS 0-1. Pts were randomized 1:1 to TV monotherapy or investigator's choice of topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed. The primary endpoint was OS. Key secondary endpoints included PFS and confirmed ORR by investigator.

Results

502 pts were randomized (TV: 253; chemotherapy: 249); median survival follow-up was 10.8 mo (95% CI, 10.3-11.6). Overall, median age was 50 yrs (range: 26-80); arms were balanced for demographics and disease characteristics. 63.9% and 27.5% of pts had prior bevacizumab and prior anti-PD-(L)1 therapy, respectively. The TV arm had a 30% reduction in risk of death vs chemotherapy (HR 0.70; 95% CI 0.54-0.89; P=0.0038), with significantly longer median OS (11.5 mo [95% CI 9.8-14.9] vs 9.5 mo [95% CI 7.9-10.7]). PFS was superior in the TV vs chemotherapy arm (HR: 0.67 [95% CI, 0.54-0.82]; P<0.0001). Confirmed ORR was 17.8% and 5.2% in the TV and chemotherapy arms, respectively (odds ratio: 4.0; 95% CI, 2.1-7.6; P<0.0001). Most pts experienced at least 1 treatment-related adverse event (TV: 87.6% [grade ≥3: 29.2%] vs chemotherapy: 85.4% [grade ≥3: 45.2%]). AEs were consistent with the known TV safety profile, including for ocular, peripheral neuropathy, and bleeding AEs.

Conclusions

In the phase 3 innovaTV 301 study, TV showed a statistically significant and clinically meaningful improvement in OS, PFS, and ORR vs chemotherapy, with a manageable and tolerable safety profile in pts with 2L/3L r/mCC.

Clinical trial identification

SGNTV-003; Amendment 3 (6 April 2022), NCT04697628.

Editorial acknowledgement

The authors thank Jennifer Yang, PhD, of Seagen Inc., who provided medical writing and editorial support in accordance with Good Publication Practices.

Legal entity responsible for the study

Seagen Inc.

Funding

This study was funded by Genmab (Copenhagen, Denmark), Seagen Inc. (Bothell, WA, USA), the Gynecologic Oncology Group (GOG), and the European Network of Gynaecological Oncological Trial Groups (ENGOT). Tisotumab vedotin is being co-developed by Genmab and Seagen.

Disclosure

I.B. Vergote: Financial Interests, Personal, Advisory Board, Consulting: Agenus (2021), Aksebio China (2021), AstraZeneca (2021-2022), Bristol Myers Squibb (2021), Deciphera Pharmaceuticals (2021), Eisai (2021), F. Hoffmann-La Roche Ltd (2021), Genmab (2021), GSK (2021), Immunogen Inc. (2021-2022), Jazzpharma (2021-2022), Karyopharm (2021), MSD (2021-2022), Novocure (2020-2022), Novartis (2021), Oncoinvent AS (2021-2022), Seagen (2021), Sotio a.s. (2021-2022); Financial Interests, Institutional, Advisory Board, Consulting: AstraZeneca (2019-2020), Deciphera Pharmaceuticals (2020), Elevar Therapeutics (2020), F. Hoffmann-La Roche Ltd (2019-2020), Genmab (2019-2020), GSK (2019-2020), Mersana (2020), MSD (2019-2020), Oncoinvent AS (2019-2020), Sotio a.s. (2019-2020), Verastem Oncology (2020), Zentalis (2020), Amgen (Europe) 2019, Clovis Oncology Inc (2019), Carrick Therapeutics (2019), Millennium Pharmaceuticals (2019); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Oncoinvent AS (2019-2020); Financial Interests, Institutional, Research Grant, Contracted Research (via KU Leuven): Genmab (2019); Financial Interests, Institutional, Research Grant, Corporate sponsored research: Amgen (2019-2020), Roche (2019-2020). A. Gonzalez Martin: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Clovis, GSK, GENMAB, Alkermes, Sutro, Roche, Sotio, PharmaMar, ONCOINVENT, Novartis, Mersana, MSD, Macrogenics, Eisai, Inmunogen, Regeneron, HederaDx, Illumina, Tubulis; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, CLOVIS, Roche, Novocure, MSD, Takeda, Zaylab; Financial Interests, Institutional, Coordinating PI, PI of ANITA trial: GSK, Roche; Financial Interests, Personal, Steering Committee Member, Member of ENGOT ov43-SC: MSD; Financial Interests, Institutional, Coordinating PI, ENGOT PI of EPIK-O trial: Novartis; Financial Interests, Institutional, Coordinating PI, ENGOT PI of AVB-500 phase III trial: Aravive. K. Fujiwara: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Takeda; Financial Interests, Personal, Advisory Board: MSD, Eisai, Genmab, Nano Carrier, Daiichi Sankyo, Seagen; Financial Interests, Personal, Other, Travel Expense: Clovis; Financial Interests, Institutional, Funding: Regenerone; Financial Interests, Institutional, Research Grant: MSD, Ono, Zeria, Genmab; Financial Interests, Personal and Institutional, Coordinating PI: AstraZeneca; Non-Financial Interests, Leadership Role: GOTIC. E. Kalbacher: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, GSK, Sanofi, Roche, GSK Tesaro, Seagen Inc; Financial Interests, Personal, Other, Travel: GSK Tesaro, Seagen Inc. S. Ghamande: Financial Interests, Personal, Invited Speaker: Esai; Financial Interests, Personal, Advisory Board, also invited speaker: GSK; Financial Interests, Institutional, Coordinating PI, Clinical trial payments: GSK, Jounce; Financial Interests, Institutional, Coordinating PI, Clinical trial payment: Merck, Esai; Financial Interests, Institutional, Coordinating PI, clinical trial payments: Mersana, AstraZeneca; Non-Financial Interests, Advisory Role: GOG foundation. J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; Financial Interests, Personal and Institutional, Local PI: Beigene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: ONO, Takeda. S. Banerjee: Financial Interests, Personal, Advisory Board: Amgen, Immunogen, Mersana, MSD, Roche, AstraZeneca, GSK, Oncxerna, Shattuck Labs, Novartis, Epsilogen, Seagen, Eisai, Regeneron, Verastem; Financial Interests, Personal, Invited Speaker: Clovis, Pfizer, AstraZeneca, GSK, Takeda, Amgen, Medscape, Research to Practice, Peerview, Novacure; Financial Interests, Personal, Stocks/Shares: PerciHealth; Financial Interests, Institutional, Research Grant: AstraZeneca, GSK; Non-Financial Interests, Principal Investigator, Phase II clinical trial Global lead, ENGOTov60/GOG3052/RAMP201: Verastem; Non-Financial Interests, Principal Investigator, ENGOT-GYN1/ATARI phase II international trial (academic sponsored): AstraZeneca; Non-Financial Interests, Principal Investigator, Academic sponsored trial PI (MONITOR-UK): GSK; Non-Financial Interests, Advisory Role, Medical advisor to UK ovarian cancer charity: Ovacome Charity; Non-Financial Interests, Leadership Role, Board Member: International Cancer Foundation (ICF). F.C. Maluf: Financial Interests, Personal, Advisory Board: MSD, BMS, AstraZeneca, Astellas, Janssen, Novartis, Roche, Pfizer, Sanofi Aventis; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, BMS, AstraZeneca, Astellas, Janssen, Novartis, Roche, Pfizer, Sanofi Aventis; Financial Interests, Personal, Other, Corporate board member: Janssen; Financial Interests, Personal, Research Funding: Janssen, MSD, BMS, AstraZeneca, Astellas, Roche, Sanofi Aventis, Regeneron. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, Immunogen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, Roche, Incyte; Non-Financial Interests, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK; Non-Financial Interests, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Member, Board of Directors: GCIG. K. Yonemori: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, Sanofi, Genmab, Gliad, OncoXerna, Takeda, Novartis, MSD; Financial Interests, Personal, Invited Speaker: Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR Pharma, MSD, Ono, BMS, Boehringer Ingelheim, Daiichi Sankyo, Bayer, Jansen, Sanofi; Financial Interests, Institutional, Local PI: MSD, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seagen, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirrin, Nihon Kayaku, Haihe. E. Van Nieuwenhuysen: Financial Interests, Institutional, Advisory Board: Regeneron, Oncoinvent; Financial Interests, Institutional, Local PI: Regeneron, Oncoinvent, Roche, Seagen, Merck, Novartis; Financial Interests, Institutional, Steering Committee Member: AstraZeneca; Financial Interests, Institutional, Coordinating PI: AstraZeneca. L.M. Manso Sanchez: Financial Interests, Personal, Full or part-time Employment: Univ Hospital 12 Octubre, Madrid; Financial Interests, Personal, Speaker’s Bureau: GSK, AstraZeneca, Novartis, Pfizer, Daiichi Sankyo, Roche; Financial Interests, Personal, Other, Travel: GSK, AstraZeneca, Roche. L. Woelber: Financial Interests, Personal, Advisory Board: GSK, Roche, MSD, Eisai, Seagen; Financial Interests, Personal, Invited Speaker: Pfizer, Roche, MSD, Seagen; Financial Interests, Personal, Other, scientific board: med update GmbH; Financial Interests, Personal, Other, speaker: med publico GmbH; Financial Interests, Institutional, Coordinating PI: Seagen, Medac Oncology; Financial Interests, Institutional, Local PI: MSD, Vaccibody AS, Roche. A. Covens: Financial Interests, Personal, Other, Honoraria: GSK; Financial Interests, Personal, Research Funding: GSK, Merck. E. Whalley: Financial Interests, Personal, Full or part-time Employment: Seagen Inc; Financial Interests, Personal, Stocks or ownership: Seagen Inc. M.S.L. Teng: Financial Interests, Personal, Full or part-time Employment: Seagen Inc; Financial Interests, Personal, Stocks or ownership: Seagen Inc. I. Soumaoro: Financial Interests, Personal, Full or part-time Employment: Genmab; Financial Interests, Personal, Stocks/Shares: Genmab. B.M. Slomovitz: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis, Eisai, GSK, Genentech, Merck, Immunogen, Novocure; Financial Interests, Personal, Other, consultant: GOG Foundation; Non-Financial Interests, Member of Board of Directors: GOG Foundation. All other authors have declared no conflicts of interest.