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Found 5 Presentations For Request "tisotumab vedotin"
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
- Ignace B. Vergote (Leuven, Belgium)
Abstract
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.
660MO - First-in-human study of SGN-B7H4V, a B7-H4-directed vedotin ADC, in patients with advanced solid tumors: Preliminary results of a phase I study (SGNB7H4V-001)
- Cesar A. Perez (Fort Myers, United States of America)
Abstract
Background
B7-H4 is a B7 immune checkpoint ligand expressed at low levels in normal tissue and is upregulated in solid tumors, including breast, ovarian, and endometrial cancers. SGN-B7H4V is an investigational vedotin ADC comprising a B7-H4-directed monoclonal antibody conjugated to monomethyl auristatin E via a protease-cleavable linker. We report first results from dose escalation (Part A) of this ongoing phase 1 study.
Methods
SGNB7H4V-001 is a first-in-human, multicenter study evaluating the safety, tolerability, pharmacokinetics, and antitumor activity (objective response rate per RECIST v1.1) of SGN-B7H4V in patients with advanced solid tumors. Part A enrolled patients with histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors irrespective of B7-H4 expression. Patients received SGN-B7H4V on Days 1 and 8 of a 21-day cycle (2Q3W, 0.75, 1.0, 1.25, or 1.5 mg/kg), or on Days 1 and 15 of a 28-day cycle (2Q4W, 1.25, 1.5, 1.75, or 2.0 mg/kg).
Results
As of 10 March 2023, 75 patients were enrolled and received SGN-B7H4V. In 2Q3W (n=35), 3 patients (8.6%) had dose-limiting toxicities (DLTs) of hyperglycemia (1.25 mg/kg), arterial embolism (1.5 mg/kg), and neutropenia (1.5 mg/kg). The most common TEAEs across doses were fatigue (20.0%), peripheral sensory neuropathy (20.0%), and neutropenia (17.1%). The most common grade ≥3 TEAE was neutropenia (14.3%). In 2Q4W (n=40), 2 of 39 DLT-evaluable patients (5.1%) had DLTs of peripheral sensory neuropathy (1.5 mg/kg) and transaminitis (2.0 mg/kg). The most common TEAEs were fatigue (27.5%), peripheral sensory neuropathy (27.5%), and nausea (22.5%). The most common grade ≥3 TEAEs were anemia, dyspnea, hypotension, and pneumonia (5.0% each). Confirmed objective responses (starting at 0.75 mg/kg) were observed in evaluable patients with breast (7/25 patients), ovarian (2/15 patients), endometrial (1 [complete response]/16 patients), and biliary tract cancers (2/9 patients).
Conclusions
SGN-B7H4V showed a manageable safety profile in patients with advanced solid tumors. Responses were observed at all tested dose levels and across various tumor types. Dose expansion in select tumor types is planned.
Clinical trial identification
EudraCT 2021-002107-35, NCT05194072; Release date: 03 April 2023.
Editorial acknowledgement
Irina Mordukhovich, PhD (MMS Holdings, Canton, MI), provided medical writing.
Legal entity responsible for the study
Seagen Inc.
Funding
Study funding was provided by Seagen Inc., Bothell, WA, USA.
Disclosure
C.A. Perez: Financial Interests, Institutional, Principal Investigator: Accutar Biotech, Dracen Pharmaceuticals, Elpiscience Biopharmaceuticals, Elucida Oncology, Genentech Inc., Hyamab Inc., Jazz Pharmaceuticals, Kinnate Biopharma, Kura Oncology, Mirati Therpeutics, Relay Therapeutics, Ribbon Therapeutics, Seagen Inc., Tallac Therapeutics, Xilio Therapeutics, Zhuhai Yufan Biotechnologies Co. J.T. Henry: Financial Interests, Personal, Full or part-time Employment, Associate Director/Oncologist: Sarah Cannon Research Institute; Financial Interests, Personal, Stocks/Shares: HCA; Financial Interests, Institutional, Invited Speaker: Abbiscko Therapeutics, ABl bio, Accutar biotech ADC therapeutics, Agenus, Aileron Therapeutics, Amgen Inc., Artios, Astrazenaca, Bicycle therapeutics, BioAlta, BioInvent pharma, Biosplice therapeutics, Black diamond therapeutics, Boehringer, Ingelheim, Cyteir, Daiichi Sankyo, Eli Lilly, Epizyme, Erasca, Exelixis, FujiFilm, GSK, Hutchison MediPharma, ICON plc, IGM Biosciences, Immunogen, Jacobio pharmaceuticals, Jounce pharma, Jubilant therapeutics, Loxo Oncology, Merck& CO, Metabomed, Molecular templates, Navire Pharma, Nikang pharmaceuticals, Oncorus, Prelude therapeutics, Poseida, PureTech, Pyramid, Rascal Therapeutics, Regeneron, Relay Therapeutics, Rgenix Inc., Ribon therapeutics, Sapience, Sarah Cannon Development Innovations, Sarah Cannon Research Institute, Seagen, Simcha Therapeutics, Siranomics, Stingthera, Synthorx Inc., Teneothree, Takeda pharmaceuticals, Tallac therapeutics, Tarveda, Tesaro, Turning point pharma, Xencor. N. Lakhani: Financial Interests, Personal, Advisory Board: Innovent Biologics; Financial Interests, Personal, Advisory Board, Participation in Ad Board: Ikena, SK Life Sciences; Financial Interests, Institutional, Invited Speaker: ALX Therapeutics, Ascentage, Constellation Pharma, Alpine Biosciences, Forty Seven, Merck, Pfizer, Regeneron, Symphogen, InhibRx, Seagen, Sapience Therapeutics, Jounce, Northern Biologics, Odonate, Loxo/Lilly, Ikena, Mersana Therapeutics, Astellas, Celgene, Helsinn, Shattuck Labs, Samumed, GSK, Alkermes, Servier, Samumed, Tizona Therapeutics, Gilead, Repare Therapeutics, Alkermes, InhibRx, Janssen, cytomX, KSQ Therapeutics, Repare Therapeutics. E.P. Hamilton: Financial Interests, Institutional, Other, Consulting/Advisory Role: Genentech/Roche, Novartis, Lilly, Pfizer, Mersana, iTeos, Janssen, Loxo, Relay Therapeutics, Olema Pharmaceuticals, Orum Therapeutics, Stemline Therapeutics, Arcus, AstraZeneca, Daiichi Sankyo, Seagen, Ellipses Pharma, Greenwich LifeSciences, Tubulis, Verascity Science, Theratechnologies; Financial Interests, Institutional, Research Grant: Oncomed, Genentech/Roche, Zymeworks, Rgenix, Arqule, Clovis, Millennium, Acerta Pharma, Sermonix Pharmaceuticals, Black Diamond, Karyopharm, Curis, Syndax, Novartis, Boehringer Ingelheim, Immunomedics, FujiFilm, Taiho, Deciphera, Molecular Templates, Onconova Therapeutics, Dana Farber Cancer Hospital, Hutchinson MediPharma, MedImmune, Seagen, Compugen, TapImmune, Lilly, Pfizer, H3 Biomedicine, Merus, Regeneron, Arvinas, StemCentRx, Verastem, eFFECTOR Therapeutics, CytomX, InventisBio, Lycera, Mersana, Radius Health, AbbVie, Nucana, Leap Therapeutics, Zenith Epigenetics, Harpoon, Orinove, EMD Serono, AstraZeneca, Tesaro, Macrogenics, Daiichi Sankyo, Syros, Sutro, G1 Therapeutics, PharmaMar, Olema, Immunogen, Plexxicon, Amgen, Akesobio Australia, Shattuck Labs, ADC Therapeutics, Aravive, Atlas MedX, Ellipses, Incyte, Jacobio, Mabspace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pionyr Immunotherapeutics, Repertoire Immune Medicine, Treadwell Therapeutics, Accutar Biotechnology, Cascadian Therapeutics, Artios, BeiGene; Financial Interests, Institutional, : Bliss BioPharmaceuticals. G. Colon-Otero: Financial Interests, Institutional, Full or part-time Employment, employed full time by the Mayo Clinic: Mayo Clinic; Financial Interests, Institutional, Invited Speaker, NIH grant 2022-2027: NIH; Financial Interests, Institutional, Invited Speaker, Co-Investigator for U54 grant with FAMU: National Institute of Minority Health; Financial Interests, Institutional, Invited Speaker, Research grant for clinical trial Y40482: A phase 1b study of cobimetinib in combination with niraparib 2019- August 2023: Hoffmann-LaRoche; Financial Interests, Institutional, Invited Speaker, Research funding for phase 1b/2trial of TG4001 and avelumab in patients with HV-16 positive recurrent or metastatic malignancies 11/21- 12/23: Transgene SA; Financial Interests, Institutional, Invited Speaker, A Phase 1 Study of SGN-B7H4V in Advanced Solid Tumors.Funded by Seagen. (SGNB7H4V-001) August 2022- July 2026: Seagen; Financial Interests, Institutional, Invited Speaker, A Randomized, Phase 2 Study of Pembrolizumab AndChemotherapy With or Without MK-4830 as NeoadjuvantTreatment for High-Grade Serous Ovarian Cancer. Funded byMerck & Co., Inc. November 2022- November 2024: Merck; Financial Interests, Institutional, Invited Speaker, (ECTx) RP-6306-02 (MCF): Phase 1 Study of the PKMYT1Inhibitor RP-6306 in Combination with Gemcitabine for theTreatment of Advanced Solid Tumors (MAGNETIC Study).Funded by Repare Therapeutics. (RP-6306-02) June 2022- May 2024: REPARE; Non-Financial Interests, Advisory Role, May 2023- no personal renumeration: REPARE; Non-Financial Interests, Member of Board of Directors: Florida Society of Clinical Oncology; Non-Financial Interests, Officer: AACR MICR Council; Non-Financial Interests, Member, Member of MICR Council: AACR. J.R. Diamond: Financial Interests, Institutional, Other, Consultant, Chief Medical Officer: OnKure Therapeutics; Financial Interests, Institutional, Advisory Board: Gilead; Financial Interests, Institutional, Other, stock options: OnKure Therapeutics; Financial Interests, Institutional, Invited Speaker, PI of clinical trial at my institution with payments to my institution: HutchMed, Gilead, Merck, Cosmo, Adlai Nortye, Takeda, Seattle Genetics, BMS. B. O’Neil: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. A. Kalyan: Financial Interests, Personal, Advisory Board, Consulting and advisory board: AstraZeneca; Financial Interests, Personal, Advisory Board, Consulting and Advisory Board: Genentech; Financial Interests, Personal, Invited Speaker, Speaking for Nurses and Doctors: Genentech; Financial Interests, Personal, Advisory Board: Exelixis, Boston Scientific; Financial Interests, Personal, Other, Consulting: Boston Scientific; Financial Interests, Institutional, Invited Speaker: Boston Scientific, Exelixis; Non-Financial Interests, Principal Investigator, Investigator: Exelixis; Non-Financial Interests, Principal Investigator: Boston Scientific. G.P. Sonpavde: Financial Interests, Personal, Advisory Board: Bicycle Therapeutics, Bristol Myers Squibb, EMD Serono/Pfizer, Exelixis, G1 Therapeutics, Genentech, Janssen, Loxo Oncology, Lucence, Merck, Sanofi, Scholar Rock, Seagen, Syapse, Tempus, Immunomedics/Gilead; Financial Interests, Personal, Advisory Board, Editor of Bladder cancer virtual center of excellence for Practice Update: Elsevier; Financial Interests, Personal, Advisory Board, to develop a trial in bladder cancer: Servier Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Exelixis, Gilead, Research to practice, Seagen, Janssen; Financial Interests, Personal, Other, Member of data safety monitoring board: Mereo; Financial Interests, Personal, Other, Author of chapter: Uptodate; Financial Interests, Institutional, Research Grant, Financial interest: EMD Serono; Financial Interests, Institutional, Research Grant, No financial interest: Gilead, Jazz Pharma, Predicine, QED, Sanofi; Non-Financial Interests, Personal, Principal Investigator, Steering committee of trial: Bristol Myers Squibb; Non-Financial Interests, Personal, Principal Investigator: G1 Therapeutics; Non-Financial Interests, Personal, Other, Steering committee of trial: Merck; Non-Financial Interests, Personal, Leadership Role, Steering committee of trial: QED; Other, Personal, Other, Spouse employment: Myriad Genetics. A.A. Awan: Financial Interests, Personal, Other, Honorarium: Apotex, Roche Canada, AstraZeneca Canada, Oncology Education, Eli Lilly, Exactis Innovation, Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor: Exact Sciences, Pfizer, Novartis Canada Pharmaceuticals Inc., Exact Sciences, Eli Lilly, Foundation Medicine, AstraZeneca Canada, Roche Canada, AstraZeneca, Gilead Sciences; Financial Interests, Institutional, Research Funding: Roche, Sermonix Pharmaceuticals, Seagen, Exactis Innovation, Intensity Therapeutics, Astellas Pharma, Canexia Health; Financial Interests, Institutional, Other, Travel/Accomodations/Expenses: Roche/Genentech. E. Fontana: Financial Interests, Personal, Invited Speaker: CARIS Life Science, Repair Therapeutics; Financial Interests, Personal, Other, Conference attendance: Sapience Pharma; Financial Interests, Personal, Full or part-time Employment: Hospital Corporation of America (HCA) International; Financial Interests, Personal, Officer: EORTC; Financial Interests, Institutional, Coordinating PI: Repair Therapeutics, Amgen, Taiho Pharmaceutical; Financial Interests, Institutional, Local PI: Bicycle Therapeutics, Artios Pharma, Seagen, Nurix Therapeutics, BioNTech SE, Relay Therapeutics, Pfizer, Roche, Daiichi Sankyo, Gilead Science, Basilea Pharmaceutica, Jiangsu Hengrui Medicine, Mereo Biopharma, HUTCHMED, Merus, Crescendo Biologics, GSK plc, BeiGene, Turning Point Therapeutics, Sapience Pharma; Non-Financial Interests, Advisory Role: Vivan Therapeutics. P. Xu, F. Zhang, N. Nazarenko: Financial Interests, Institutional, Full or part-time Employment: Seagen Inc.; Financial Interests, Institutional, Stocks/Shares: Seagen Inc. A. Patnaik: Financial Interests, Institutional, Other, Institutional research funding: Compugen. All other authors have declared no conflicts of interest.
2365MO - Study EV-103 cohort L: Perioperative treatment w/ enfortumab vedotin (EV) monotherapy in cisplatin (cis)-ineligible patients (pts) w/ muscle invasive bladder cancer (MIBC)
- Srikala Sridhar (Toronto, Canada)
Abstract
Background
Current SOC for pts w/ MIBC is neoadjuvant cis-based chemotherapy followed by radical cystectomy and pelvic lymph node dissection (RC+PLND). For pts who are cis-ineligible, SOC is RC+PLND alone but adjuvant therapy may be recommended. Due to high rates of recurrence in cis-ineligible pts, an urgent unmet need remains. Neoadjuvant EV showed promising antitumor activity in MIBC (pathological CR [pCR] of 36%, pathological downstaging [pDS] of 50%) in EV-103 Cohort H ( Petrylak 2022 ). Cohort L examines a perioperative approach.
Methods
Cohort L enrolled pts who are cis-ineligible w/ previously untreated MIBC (cT2-T4aN0M0 or cT1-T4aN1M0) who are medically fit for and agree to undergo curative intent RC+PLND within 12 wks. Pts received 3 cycles of neoadjuvant EV (1.25mg/kg) on Days 1 and 8 of each 3-week cycle followed by RC+PLND and then 6 cycles of adjuvant EV (1.25 mg/kg) on Days 1 and 8 of every 3 week cycle starting 8 weeks post-RC. Primary endpoint is pathological CR (pCR) per central pathology review; secondary endpoints include pathological downstaging (pDS) rate per central pathology review, safety and tolerability. Here we present initial results from the neoadjuvant/RC+PLND phase + 30 days post surgery.
Results
52 pts were enrolled. 51 pts were treated w/ EV in the neoadjuvant phase w/ a median of 3 cycles; 42 pts (82.4%) completed RC+PLND. One pt achieved clinical CR and elected not to undergo RC+PLND and was excluded from pCR and pDS analyses; 17/50 (34.0%) pts had a pCR. pDS was seen in 21/50 (42.0%) pts. In the neoadjuvant/RC+PLND phase, of 51 treated pts most common EV-related TEAEs were fatigue (52.9%), rash maculo-papular (31.4%), and nausea (29.4%). 39.2% of pts had an EV-related TEAE ≥ grade 3; 31.4% pf pts had a RC-related TEAE ≥ grade 3. No surgeries were delayed due to EV-related TEAEs. One pt (2.0%) experienced an EV-related death (Stevens-Johnson syndrome) before surgery.
Conclusions
EV continues to show promising activity and was tolerable in cis-ineligible pts w/ MIBC in this ongoing trial. Both the efficacy and safety profiles were consistent with previously reported data from Cohort H. These data support the ongoing phase 3 trials evaluating EV + pembrolizumab in MIBC.
Clinical trial identification
EudraCT 2018-001527-39; Release Date: Amendment 11, 15-Feb-2023.
Editorial acknowledgement
Sarah Canestaro, MS, of Populus Group, Troy, MI, supported by Seagen Inc. for providing medical writing and editorial support.
Legal entity responsible for the study
Astellas Pharma Global Development, Inc.
Funding
Seagen Inc., Bothell, WA, USA and Astellas Pharma, Northbrook, IL.
Disclosure
S. Sridhar: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bayer, BMS, Eisai, EMD Serono, Hoffmann La Roche, Pfizer; Financial Interests, Institutional, Research Grant, Unrestricted Research grant to institution for developing a database: Seagen; Financial Interests, Institutional, Research Grant: Bayer, Janssen. P.H. O'Donnell: Financial Interests, Personal, Other, Honoraria: Merck, Astellas Pharma, Pfizer, CLD, Axiom Healthcare Strategies, EMD Serono, IntrinsiQ Specialty Solutions, ISMIE, NAMCP, Seagen, Curio Science, FirstWord Publications, MedLearning Group, Research to Practice, Great Debates and Updates, MJH Life Sciences, Peerview, Vaniam Group, EnquiringMinds; Financial Interests, Institutional, Funding, Research Funding: Boehringer Ingelheim, Merck, Genentech/Roche, AstraZeneca/MedImmune, Acerta Pharma, Janssen, Seagen, Bristol Myers Squibb, Astellas Pharma; Other, Personal, Expert Testimony: Oregon Health & Science University (OHSU); Other, Personal, Other, Travel, Accommodations, Expenses: Curio Science; Other, Personal, Other Relationship: Janssen, Nektar, NIH, Dragonfly Therapeutics, G1 Therapeutics. T.W. Flaig: Financial Interests, Personal, Other, Consulting and advisory: Seattle Genetics; Financial Interests, Institutional, Member of Board of Directors: Joint Venture between University of Colorado and UCHealth; Financial Interests, Personal, Stocks/Shares, I am founder and stockholder in this academic start up company. We are submitting SBIR grants for a patent on work done in our lab. There are no commercial products or current clinical trials - early stage: Aurora Oncology; Financial Interests, Personal, Other, We have a patent with the University of Colorado (from our lab) which has been licensed to Aurora Oncology (I am a cofounder of this faculty start up): Aurora Oncology; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Janssen Oncology, Sanofi, Pfizer, Roche - Genentech, AstraZeneca/MedImmune, Lilly, Astellas, Seattle Genetics, Seagen, Merck, La Roche - Posay, Myovant Sciences. J.E. Rosenberg: Financial Interests, Personal, Advisory Board: Alligator Biosciences, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, EMD-Serono, Genentech, Gilead, Infinity Pharmaceuticals, Janssen, Lilly Oncology, Merck, Mirati, NCCN, Pfizer, QED Therapeutics, Seagen, Tyra Biosciences, Hengrui; Financial Interests, Personal, Invited Speaker, Medical Education: Clinical Care Options; Financial Interests, Personal, Invited Speaker: EMD-Serono; Financial Interests, Personal, Invited Speaker, Medical education: MJH Associates, Physicians Education Resource, Research to Practice; Financial Interests, Personal, Royalties: Wolters Kluyer/Uptodate; Financial Interests, Institutional, Invited Speaker, Coordinating PI of rogaratinib/atezolizumab trial; consultant, trial open at my institution: Bayer; Financial Interests, Personal and Institutional, Invited Speaker, EV-201, EV- 103; consultant, trial open at my institution: Seagen; Financial Interests, Personal and Institutional, Invited Speaker, EV-301, consultant, trial open at my institution: Astellas; Financial Interests, Institutional, Invited Speaker, Consultant, PI of trial, trial open at my institution: AstraZeneca; Financial Interests, Institutional, Invited Speaker, PI of IMVIGOR210 (still open at my institution): Genentech; Financial Interests, Institutional, Invited Speaker, Investigator initiated trial at my institution: QED; Non-Financial Interests, Leadership Role, Bladder Cadre leader for Alliance (NCTN): Alliance for Clinical Trials in Oncology. C.J. Hoimes: Financial Interests, Personal, Advisory Board: Astellas, BMS, Foundation Medicine, Merck &Co, Seagen, Tempus; Financial Interests, Personal, Invited Speaker: BMS, Eisai; Financial Interests, Institutional, Advisory Board: Dynavax; Financial Interests, Institutional, Invited Speaker: AbbVie, Alkermes, Astellas, BMS, Bayer, Bellicum, BioNTech, Dynavax, Genentech, Janssen, Mirati, NeoImmune Tech, Pfizer, Phosplatin, Prometheus; Financial Interests, Personal and Institutional, Invited Speaker: Merck &Co, Seagen. M.I. Milowsky: Financial Interests, Personal, Advisory Board: Loxo/Lilly; Financial Interests, Personal, Other, Co-Editor-in-Chief, Clinical Genitourinary Cancer: Elsevier; Financial Interests, Personal, Invited Speaker: Medscape; Financial Interests, Personal, Stocks/Shares: Pfizer, Merck, Gilead Sciences; Financial Interests, Institutional, Invited Speaker: Merck, Roche/Genentech, Bristol Myers Squibb, Mirati Therapeutics, Incyte, Seagen, G1 Therapeutics, Alliance Foundation Trials, Alliance for Clinical Trials in Oncology, Clovis Oncology, Arvinas, Regeneron. S. Srinivas: Financial Interests, Invited Speaker: Seagen. S. George: Financial Interests, Personal, Advisory Board, advisor/consultant: BMS, Bayer, Pfizer, Exelixis, Corvus, Sanofi/ Genzyme, Seattle Genetics, EMD Serono, Eisai, Merck, Aveo, QED therapeutics; Financial Interests, Institutional, Invited Speaker: Pfizer, Merck, Agensys, Novartis, BMS, Bayer, Eisai, Seattle Genetics, Calithera, Corvus, Surface Oncology, Exelixis, Aravive, Aveo, Gilead. R.R. McKay: Financial Interests, Personal, Advisory Board: Aveo, AstraZeneca, Bayer, Calithera, Dendreon, Exelixis, JNJ, Merck, Pfizer, Sanofi, Tempus, BMS, Lilly, Sanofi, SeaGen, Telix, Sorrento Therapeutics; Financial Interests, Personal, Other, Molecular tumor board: Caris; Financial Interests, Personal, Other, Consultant: Dendreon, Myovant; Financial Interests, Personal, Invited Speaker: Exelixis, Merck, Novartis, Pfizer; Financial Interests, Invited Speaker: Aveo, JNJ, SeaGen, Bayer, AstraZeneca, Calibr, Poseida, Oncternal, Scholar Rock, Merck, Xencor, Genentech, Eli Lilly, BMS; Financial Interests, Institutional, Invited Speaker: Exelixis. D.P. Petrylak: Financial Interests, Personal, Other, Consultant Fees: Ada Cap (Advanced Accelerator Applications), Amgen, Astellas, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Exelixis, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Ipsen, Janssen, Merck & Company Inc, Mirati, Monopteros, Pfizer, Pharmacyclics, Regeneron, Roche, Sanofi Aventis Pharmaceuticals, Seattle Genetics, Urogen; Financial Interests, Personal, Stocks/Shares: Bellicum (Sold 7/2020), Tyme (sold 10/2019); Financial Interests, Institutional, Invited Speaker: Ada Cap (Advanced Accelerator Applications), Agensys Inc, Arvinas, Astellas, AstraZeneca, Bayer, BioXcel Therapeutics, Bristol Myers Squibb, Clovis Oncology, Daiichi Sankyo Company Limited, Eisai, Eli Lilly, Endocyte, Ferring, Genentech, Gilead Sciences, Innocrin, MedImmune, Medivation, Merck, Mirati, Novartis, Pfizer, Progenics, Replimune, Roche, Sanofi Aventis, Seattle Genetics. P.M. Coelho Barata: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Eisai, Exelixis, Janssen, EMD Serono, Dendreon, Pfizer, Seattle Genetics, BMS, Bayer; Financial Interests, Personal, Invited Speaker: Caris Life Sciences, UroToday. C. Hwang: Financial Interests, Personal, Other, Consultant: Tempus; Financial Interests, Personal, Advisory Board: EMD Sorono, Genzyme (Sanofi), Dendreon; Financial Interests, Personal, Stocks/Shares: Johnson and Johnson; Financial Interests, Institutional, Invited Speaker: Merck, Seagen, AstraZeneca, Bayer; Non-Financial Interests, Sponsor/Funding: Henry Ford Health System Government Affairs Services Pac. M. Cruz-Correa: Financial Interests, Institutional, Research Grant: Merck, SeaGen, BMS, Taiho, Pfizer, Janssen, AbbVie, Genentech, Incyte, Huyabio, BeiGene. M. Iafolla: Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Bayer, Canadian Urologic Association, Ipsen, Merck, Sanofi, Save Your Skin, Sermo Team; Financial Interests, Personal, Expert Testimony: CompassMD, MD Analytics; Financial Interests, Personal, Full or part-time Employment: William Osler Health System; Financial Interests, Institutional, Research Grant: EMD Serono, Pfizer, Bristol Myers Squibb, Novartis; Non-Financial Interests, Principal Investigator: Seagen, Pfizer, Bristol Myers Squibb, AstraZeneca, Astellas Pharma Global Development Inc. M. Mckean: Financial Interests, Institutional, Research Grant: Aadi Biosciences, Accutar Biotechnology, Alpine Immune Sciences, Arcus Biosciences, Arvinas, Ascentage Pharma Group, Astellas, Bayer, Bicycle Therapeutics, BioMed Valley Discoveries, BioNTech, Dragonfly Therapeutics, EMD Serono, Epizyme, Erasca, Exelixis, Foghorn Therapeutics, G1 Therapeutics, Genentech, Gilead Sciences, GSK, Ideaya Biosciences, Ikena Oncology, ImmVira Pharma, Infinity Pharmaceuticals, Jacobio Pharmaceuticals, Kechow Pharma, Kezar Life Sciences, Kinnate BioPharma, MedImmune, Mereo BioPharma, Metabomed, Moderna, NBE Therapeutics, Nektar, Novartis, OncoC4, Oncorus, PACT Pharma, Pfizer, Plexxikon, Poseida, Prelude Therapeutics, Pyramid Biosciences, Regeneron, Sapience Therapeutics, Scholar Rock, Seagen, Synthrox, Takeda Pharmaceuticals, Teneobio, Tempest Therapeutics, Tizona Therapeutics, Tmunity Therapeutics, TopAlliance Biosciences, Xilio; Financial Interests, Institutional, Advisory Role: Astellas Pharma, AstraZeneca, BicycleTX Limited, Castle Biosciences, Eisai, Ideaya Biosciences, IQVIA, iTeos, Merck, Moderna, Pfizer. R. Dreicer: Financial Interests, Personal, Advisory Board: Pfizer, Eisai, Propella, Merck, Astellas, Janssen, Giliead, Sanofi Genzyme; Financial Interests, Personal, Other, DSMB: Aveo; Financial Interests, Institutional, Funding: Exilexis, Novartis. S. Brancato: Financial Interests, Personal, Full or part-time Employment: Astellas Pharma Global Development. J.J. Lukas: Financial Interests, Personal, Full or part-time Employment, Medical Monitor: Seagen; Financial Interests, Institutional, Full or part-time Employment, Assistant Clinical Professor: University of Washington; Financial Interests, Personal, Stocks/Shares: Seagen. Y. Yu: Financial Interests, Personal, Full or part-time Employment, Full time employee: Seagen Inc; Financial Interests, Personal, Stocks/Shares: Seagen inc. H. Moon: Financial Interests, Institutional, Invited Speaker, clinical trial PI: Seagen; Financial Interests, Personal and Institutional, Invited Speaker, Steering Committee: EMD Serono; Financial Interests, Institutional, Invited Speaker, PI for Clinical trial: Janssen; Financial Interests, Institutional, Invited Speaker, PI for Trial: Nektar; Financial Interests, Invited Speaker, Clinical trial PI: Huya; Non-Financial Interests, Other, Grant Proposal Review committee for NCCN/Pfizer Bladder cancer grant review committee: NCCN; Non-Financial Interests, Advisory Role, NCI Prostate Cancer task force: NCI.
2360O - The double antibody drug conjugate (DAD) phase I trial: Sacituzumab govitecan (SG) plus enfortumab vedotin (EV) as ≥ second-line therapy for metastatic urothelial carcinoma (mUC)
- Bradley A. McGregor (Boston, United States of America)
Abstract
Background
Antibody-drug conjugates are a mainstay in treatment of mUC. Given different targets, payloads with non-overlapping toxicities and preclinical synergy of SG with anti-microtubule agents, we evaluated the safety and efficacy of SG+EV in a phase I trial (NCT04724018).
Methods
Patients (pts) with mUC and ECOG ≤1 who progressed on platinum and immunotherapy or were cisplatin ineligible and received one line of therapy were enrolled. SG+EV were dosed D1,8 of a 21-day cycle until progression of unacceptable toxicity. To assess the feasibility and safety of combining SG+EV, doses were adjusted based on the incidence of dose-limiting toxicities (DLTs) during cycle(C) 1 and the total number of pts treated at four pre-specified dose levels (DL) using a Bayesian Optimal Interval design (Table). Adverse events (AE) were assessed using CTCAE 5.0.
Results
24 pts were enrolled (9 DL1, 9 DL2, 6 DL3) from 5/2021 to 4/2023. At data cutoff on May 1, 2023, 23 pts were evaluable for DLT assessment; one pt in DL3 never started therapy. Median age was 69 years (range 41-88); 22 received ≥ 2 lines of therapy. After 2 pts in DL1 experienced febrile neutropenia (FN) prophylactic granulocyte stimulating factor (GCSF) was permitted; 18 pts received GCSF. 70% pts experienced ≥ grade 3 AE at any DLs with one grade 5 AE (pneumonitis possibly related to EV) during C2 (pt in DL3.) The table summarizes DLTs at corresponding DLs; DL2 has been selected for future studies. Among 21 pts evaluble for response, objective response rate was 71% (15/21, 90% Confidence interval: 51-87) with 2 complete and 13 partial responses; 2 pts had progressive disease. With median follow-up 11.9 months, 11/15 responses are ongoing from 1.1+ to 21.6+ months.
DL SG dose (mg/kg) EV dose (mg/kg) N enrolled DLT -1 6 1 0 NA 1 8 1 9 2 (FN) 2 8 1.25 9 1 (delay C2D1 > 3 wks) 3 10 1.25 6 (1 not evaluable) 3 (grade 3 mucositis, delay C2D1 > 3 wks, FN)
Conclusions
SG+EV was safe with an ORR of 71% in pts with treatment refractory UC. Further DAD expansion cohorts in treatment refractory and naïve setting are in development; triplet therapy with immunotherapy is being explored.
Clinical trial identification
NCT04724018.
Legal entity responsible for the study
Dana Farber Cancer Institute.
Funding
Gilead.
Disclosure
B.A. McGregor: Financial Interests, Personal, Advisory Board: Exelixis, BMS, Dendreon, SeaGen, Astellas, Eisai, Pfizer; Financial Interests, Personal, Invited Speaker: EMD Serono, SeaGen; Financial Interests, Institutional, Trial Chair: Pfizer, Exelixis, Exelixis, BMS, Gilead; Financial Interests, Institutional, Local PI: Calithera, SeaGen, Aveo; Non-Financial Interests, Member: ASCO. G.P. Sonpavde: Financial Interests, Personal, Advisory Board: EMD Serono/Pfizer, Bristol Myers Squibb, Genentech, Merck, Sanofi, Seattle Genetics, Exelixis, Janssen, Bicycle Therapeutics, Immunomedics/Gilead, Scholar Rock, G1 Therapeutics, Loxo Oncology, Lucence, Tempus, Syapse; Financial Interests, Personal, Advisory Board, Editor of Bladder cancer virtual center of excellence for Practice Update: Elsevier; Financial Interests, Personal, Other, Member of Data Safety Monitoring Board: Mereo; Financial Interests, Personal, Other, Author of chapter: Uptodate; Financial Interests, Personal, Invited Speaker: Research to practice, Seattle Genetics, Gilead, Exelixis, Janssen; Financial Interests, Personal, Advisory Board, to develop a trial in bladder cancer: Servier Pharmaceuticals; Financial Interests, Institutional, Research Grant: Sanofi, Gilead, QED, Predicine, EMD Serono, Jazz Pharma; Non-Financial Interests, Principal Investigator, Steering committee of trial: Bristol Myers Squibb; Non-Financial Interests, Principal Investigator: G1 Therapeutics; Non-Financial Interests, Leadership Role, steering committee of trial: QED; Non-Financial Interests, Other, steering committee of trial: Merck; Other, Spouse employment: Myriad Genetics. X. Gao: Financial Interests, Personal, Advisory Board: Bayer, Flare Therapeutics, Silverback Therapeutics, PureTech, Myovant Sciences, PathAI; Financial Interests, Institutional, Local PI: Arvinas, Exelixis, Harpoon Therapeutics, Aprea Therapeutics, Takeda, Aravive, Merck, Poseida Therapeutics, TopAlliance BioSciences, Novartis, Regeneron, ALX Oncology; Financial Interests, Institutional, Coordinating PI: Bayer. C. Mantia: Financial Interests, Personal, Advisory Board, I participated in a one-time advisory board: Aadi Bioscience; Financial Interests, Institutional, Coordinating PI, Institutional funding for research: Bristol Myers Squibb. X.X. Wei: Financial Interests, Personal, Advisory Board: novartis; Financial Interests, Institutional, Coordinating PI: Bristol Myers Squibb. J.E. Berchuck: Financial Interests, Personal, Invited Speaker, Speaker honoraria: Guardant; Financial Interests, Personal, Advisory Board, Consulting fees: Genome Medical, Oncotect, Precede, TracerDx; Financial Interests, Personal, Writing Engagement: Digital Science Press; Financial Interests, Personal, Stocks/Shares: Cityblock Health, Genome Medical, Oncotect, Precede, TracerDx. M.D. Michaelson: Financial Interests, Personal, Advisory Board: Merck, Eisai, Exelixis, Janssen. T.K. Choueiri: Financial Interests, Personal, Advisory Board, Advice on GU/RCC drugs: BMS, Pfizer, Merck, Exelixis, AstraZeneca; Financial Interests, Personal, Advisory Board, Advice on Onc drugs: Lilly, EMD Serono, Infinity; Financial Interests, Personal, Advisory Board, Advice on RCC drug: Calithera; Financial Interests, Personal, Invited Speaker, RCC drug: Ipsen; Financial Interests, Personal, Advisory Board, Advice on GU Onc drugs: Surface Oncology; Financial Interests, Personal, Other, Consultant on onc drugs: Analysis Group; Financial Interests, Personal, Invited Speaker, CME, ww2.peerview.com: Peerview; Financial Interests, Personal, Invited Speaker, CME, gotoper.com: PER; Financial Interests, Personal, Invited Speaker, CME, researchtopractice.com: ResearchToPractice; Financial Interests, Personal, Invited Speaker, National Association of Managed Care: NAMC; Financial Interests, Personal, Invited Speaker, ASCO-related event: ASCO-SITC; Financial Interests, Personal, Other, Grant review to Orien Network: Orien; Financial Interests, Personal, Advisory Board, Advising oncology strategy: Aptitude Health; Financial Interests, Personal, Invited Speaker, Best of ASCO19 talk: Advent health; Financial Interests, Personal, Invited Speaker, Best of ESMO20 talk: UAE Society of Onc; Financial Interests, Personal, Invited Speaker, CME, mjhlifesciences.com (OncLive): MJH life sciences; Financial Interests, Personal, Invited Speaker, Grand Rounds: MDACC; Financial Interests, Personal, Invited Speaker, RCC webinar: Cancernet; Financial Interests, Personal, Invited Speaker, CME, Kidney Cancer Association: France Foundation; Financial Interests, Personal, Invited Speaker, CME, RCC: Springer, WebMed; Financial Interests, Personal, Invited Speaker, CME, ImmunoOncology in RCC: ASiM, CE; Financial Interests, Personal, Invited Speaker, CME, PodCast in RCC: Caribou Publishing; Financial Interests, Personal, Invited Speaker, Reimbursement: Kidney Cancer Association; Financial Interests, Personal, Other, member of the DSMB for clinical trial: Aravive; Financial Interests, Personal, Other, on the DMC of clinical trial: Aravive; Financial Interests, Personal, Advisory Board, GU cancer drug development: alkermes, Gilead; Financial Interests, Personal, Member of Board of Directors, unpaid: ACCRU; Financial Interests, Personal, Member of Board of Directors, Unpaid: KidneyCan; Financial Interests, Personal, Other, External Advisory Board Member: Gustave Roussy; Financial Interests, Personal, Stocks/Shares: Pionyr (not publicly traded), Tempest (publicly traded), Osel (not publicly traded), Nuscan (not publicly traded), Curesponse; Financial Interests, Personal, Royalties, For writing and updating chapters in GU Oncology: Up-To-Date online textbook; Financial Interests, Institutional, Funding, National Chair: BMS, Merck, Takeda, Exelixis, AstraZeneca, Tracon, Peloton; Financial Interests, Institutional, Local PI: Roche, Surface Oncology, GSK; Financial Interests, Institutional, Funding, National Co-Chair: Pfizer, EMD-Serono; Financial Interests, Institutional, Funding, Chair of trial: Lilly; Financial Interests, Institutional, Funding, SC member: Eisai; Financial Interests, Institutional, Funding, National co-chair on 3 ongoing trials: ALLIANCE Cooperative Group; Financial Interests, Institutional, Research Grant, for GU oncology translational research through IION program: BMS; Financial Interests, Institutional, Research Grant, for GU oncology translational research: Exelixis; Financial Interests, Institutional, Research Grant, For Health outcomes research: Roche; Financial Interests, Institutional, Local PI, leads trials as PI: Nikang; Non-Financial Interests, Leadership Role, Co-Chair of the meeting, 2019: Kidney Cancer Research Summit of KidneyCAN; Non-Financial Interests, Principal Investigator, Trial Global and National PI with GU Cancers, mostly Kidney Cancer: Multiple Academic and Industry entities; Non-Financial Interests, Personal, Other, Track Leader/Session chair/Speaker/Discussant: ASCO; Non-Financial Interests, Personal, Other, Speaker/Discussant/Track Leader: ESMO; Non-Financial Interests, Institutional, Other, Access to genomic database: Foundation Med, Guardant, Invitae; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Personal, Other, Grants reviewers: AACR; Non-Financial Interests, Personal, Other, Reviewer of papers: Various journals (e.g. NEJM, Lancet, JCO); Non-Financial Interests, Personal, Other, Medical writing and editorial assistance support (e.g. ClinicalThinking, Envision Pharma Group, Fishawack Group of Companies, Health Interactions, Parexel, Oxford PharmaGenesis, pharmagenesis, and others). However, first draft frequently initiated by myself when I am 1st author: Medical Communication; Non-Financial Interests, Other, Political vote usually as “independent”, not a member of any political party. I am an issue voter: General US Politics; Other, Employee at DFCI. I am also the past President of Medical Staff at DFCI 2015-2018: Dana-Farber Cancer Institute (DFCI); Other, Professor (non-profit school): Harvard Medical School (HMS); Other, No financial interest. Institutional. Filed patents related to biomarkers of immune checkpoint blockers, and circulating free methylated DNA. No money made and some patents were abandoned: Filed patents. J. Bellmunt: Financial Interests, Personal, Advisory Board, Joined the Global adboard this year: Pfizer; Financial Interests, Personal, Advisory Board, Regular GU adboard for bladder cancer: AstraZeneca; Financial Interests, Personal, Invited Speaker, Lectures in the setting of National meetings: Merck; Financial Interests, Personal, Advisory Board, Bladder adboard: Merck; Financial Interests, Personal, Advisory Board, For the adjuvant study CM 247: BMS; Financial Interests, Personal, Invited Speaker, For ESMO Asia Symp 2020 : MSD; Financial Interests, Personal, Stocks/Shares, Holdings: Bicycle; Financial Interests, Personal, Royalties, Role as Section Editor for Bladder: UpToDate; Financial Interests, Institutional, Coordinating PI, Pi of INDUCOMAIN Study (Avelumab first line in unfit patients) Though APRO Association: MSD; Financial Interests, Institutional, Coordinating PI, Pi of Prostate Study (Avelumab + Carboplatin) Though APRO Association: Pfizer; Non-Financial Interests, Other, Steering committee member of IMvigor 011: Genentech; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.
LBA6 - EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC)
- Thomas B. Powles (London, United Kingdom)
Abstract
Background
Platinum-based chemo is the standard of care (SOC) for la/mUC. An unmet need remains as long-term outcomes are poor. Here we present EV-302, a global, phase 3, open-label, randomized study evaluating EV+P in patients (pts) with previously untreated la/mUC who were eligible for cisplatin- or carboplatin-containing chemo.
Methods
Pts with previously untreated la/mUC (regardless of PD-L1 expression) were randomized 1:1 to receive 3-week cycles of EV (1.25 mg/kg; IV) on Days 1 and 8 and P (200 mg; IV) on Day 1 or gemcitabine with cisplatin or carboplatin. Dual primary endpoints were PFS per RECIST v1.1 by BICR and OS. Select secondary endpoints included overall response rate (ORR) and safety.
Results
886 pts (EV+P: 442; chemo: 444) were randomized; pt characteristics were balanced between arms. At data cutoff, median follow-up was 17.2 mo. PFS was significantly prolonged with EV+P vs chemo, reducing the risk of progression or death by 55% (median PFS, 12.5 mo vs 6.3 mo, respectively; HR 0.45 [95% CI: 0.38-0.54]; P<0.00001). OS was significantly prolonged with EV+P vs chemo, reducing the risk of death by 53% (median OS, 31.5 mo vs 16.1 mo, respectively; HR 0.47 [95% CI: 0.38-0.58]; P<0.00001). Confirmed ORR was 67.7% and 44.4% in the EV+P and chemo arms, respectively (P<0.00001). Grade ≥3 TRAEs occurred in 55.9% with EV+P and 69.5% with chemo; most common were maculopapular rash (7.7%), hyperglycemia (5.0%), and neutropenia (4.8%) for EV+P and anemia (31.4%), neutropenia (30.0%), and thrombocytopenia (19.4%) for chemo. Most common (≥5% ) grade ≥3 TRAEs of special interest for EV included skin reactions (15.5%), peripheral neuropathy (6.8%), and hyperglycemia (6.1%). Most common (≥5% ) grade ≥3 treatment-emergent AEs of special interest for P included severe skin reactions (11.8%).
Conclusions
EV+P significantly improved outcomes in pts with previously untreated la/mUC, nearly doubling the median PFS and OS vs chemo. The safety profile was generally manageable with no new safety signals. These results support EV+P as a new SOC for 1L la/mUC.
Clinical trial identification
NCT04223856.
Editorial acknowledgement
Medical writing support was provided by Thien Nguyen, Pharm D. (Seagen Inc.) and Sarah Canestaro, MS, of Populus Group, Troy, MI, supported by Seagen Inc.
Legal entity responsible for the study
Astellas Pharma.
Funding
Funded by Seagen Inc., Bothell, WA, USA; Astellas Pharma, Northbrook, IL, USA; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
T.B. Powles: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers-Squibb, Exelixis, Incyte, Ipsen, Merck, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche, Pfizer, MSD, AstraZeneca, Ipsen; Financial Interests, Personal, Other, Sponsorship for Uromigos Podcast: Mashup Ltd; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bristol Myers-Squibb, Exelixis, Ipsen, Merck, MSD, Seattle Genetics, Novartis, Pfizer, Merck Serono, Astellas, Johnson & Johnson, Eisai. B. Perez Valderrama: Financial Interests, Personal, Advisory Board: Pfizer, Astellas Pharma, Bristol-Myers Squibb, Ipsen, EUSA Pharma, Merck, MSD, AstraZeneca, AAA; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb, Roche, Bayer, EUSA Pharma, MSD, Merck, Pfizer, Janssen, Astellas Pharma, AAA. S. Gupta: Financial Interests, Personal, Advisory Board: Seattle Genetics, BMS, Pfizer, Bayer, Merck, Gilead, Loxo Oncology, Guardant, Foundation one; Financial Interests, Personal, Other, Speaker's Bureau: Janssen; Financial Interests, Personal, Other, Consultant: EMD Sorono; Financial Interests, Personal, Invited Speaker: Gilead; Financial Interests, Personal, Stocks/Shares: BioNTech, Moderna; Financial Interests, Personal, Steering Committee Member: BMS, Merck, Seattle Genetics, Acrivon; Financial Interests, Institutional, Local PI: EMD Serono, Gilead, Roche, QED, Exelixis, Moderna. J. Bedke: Financial Interests, Personal, Advisory Board: AstraZeneca, Astellas, Eisai; Financial Interests, Personal, Advisory Board and Speaker´s Bureau: BMS, Ipsen, MSD, Merck Serono, Pfizer, Roche, Janssen; Financial Interests, Institutional, Advisory Board: BMS, Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, Eisai, Novartis, Nektar; Financial Interests, Institutional, Invited Speaker: Astellas, BMS, MSD, Ipsen, Pfizer, Roche, Seagen; Other, Member of the Renal Cell Carcinoma Guidelines Panel: European Association of Urology. E. Kikuchi: Financial Interests, Personal, Invited Speaker: MSD, Bristol, Janssen, Astellas, Merck Biopham, Nippon Kayaku, Pfizer; Financial Interests, Personal, Advisory Board: Astellas, MSD, Bristol; Financial Interests, Institutional, Research Grant: Takeda, Nippon Kayaku, Kyorin, Taiho, Nippon Shinyaku. C. Vulsteke: Financial Interests, Personal, Advisory Board: MSD, Janssen-Cilag, GSK, Astellas Pharma, BMS, Leo Pharma, Bayer, AstraZeneca, Pfizer, Merck; Financial Interests, Institutional, Research Grant, Funding for research project on immune related toxicities: MSD. D.E. Castellano Gauna: Financial Interests, Personal, Advisory Board: Pfizer, Roche, BMS, Janssen, Astellas, MSD, Ipsen, AstraZeneca, Novartis, GSK; Financial Interests, Institutional, Local PI: Pfizer, Roche, MSD, BMS, AstraZeneca, Janssen, Astellas, Ipsen, Exelisis, Eisai, Lilly, Bayer, GSK, Clovis, QED Therapeutics; Non-Financial Interests, Personal, Other, Executive member: SOGUG (Spanish Oncology Genito-Urinary Group) Foundation. J. Li: Financial Interests, Personal, Invited Speaker: Astellas, Janssen Pharma, Bayer Pharmaceuticals, AstraZeneca, Ono Pharmaceutical, Merck, MSD, Roche, Synmosa, Pfizer, COOK. M. Gumus: Financial Interests, Institutional, Invited Speaker: Pfizer, Gen Pharmaceuticals, Novartis, Bayer, Amgen; Financial Interests, Institutional, Advisory Board: Amgen, Roche, BMS, AstraZeneca; Financial Interests, Institutional, Local PI: Jounce Therapeutics. N. Mar: Financial Interests, Personal, Invited Speaker: Eisai, Aveo, Tempus, Seattle Genetics; Financial Interests, Personal and Institutional, Funding, Funding for investigator initiated trial: Gilead. S. Narayanan: Financial Interests, Institutional, Full or part-time Employment: Seagen Inc; Financial Interests, Institutional, Stocks/Shares: Seagen Inc. X. Yu: Financial Interests, , Full or part-time Employment: Seagen; Financial Interests, Stocks/Shares: Seagen. S. Gorla: Financial Interests, Personal, Full or part-time Employment, I have been a full time employee of Astellas since 2012 and part of my role involves review of publications and other documents regarding the clinical trials we have conducted involving our products: Astellas; Non-Financial Interests, Project Lead, I have been a full time employee of Astellas since 2012 and have a leadership role in the projects that I lead: Astellas; Non-Financial Interests, Personal, Proprietary Information, I have been a full time employee of Astellas since 2012 and therefore have access to company confidential information about our products: Astellas. B. Homet Moreno: Financial Interests, Full or part-time Employment: Merck; Financial Interests, Proprietary Information: Merck. M.S. van der Heijden: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS, Janssen, MSD, Seagen, Pfizer; Financial Interests, Institutional, Funding, Investigator-initiated trial: BMS, Roche, AstraZeneca, 4SC; Financial Interests, Institutional, Invited Speaker, Local PI + SSC member: BMS, AstraZeneca, MSD, Seagen; Financial Interests, Institutional, Invited Speaker, Local PI + study co-PI: Janssen; Financial Interests, Institutional, Local PI: GSK. All other authors have declared no conflicts of interest.