746P EV-201: Long-term results of enfortumab vedotin monotherapy for locally advanced or metastatic urothelial cancer previously treated with platinum and PD-1/PD-L1 inhibitors

Abstract

Background: Locally advanced or metastatic urothelial carcinoma (la/mUC) is an incurable disease with poor overall survival (OS), particularly in patients (pts) who progress on or after platinum-containing chemotherapy (Pt-CC). While OS data following PD-1/PD-L1 inhibitor (i) and Pt-CC are limited, data in earlier lines (post-Pt-CC) show a 7.4 mo median (md) OS with a 30.7% 12 mo OS rate for taxanes/vinflunine (Bellmunt 2017). In Dec 2019, enfortumab vedotin (EV), a Nectin-4 directed antibody-drug conjugate comprised of a fully human monoclonal antibody linked to the microtubule-disrupting agent monomethyl auristatin E was granted accelerated approval in adult pts with la/mUC who previously received PD-1/PD-L1-i and Pt-CC in the neoadjuvant/adjuvant, la/m setting. Approval was based on data as of 01 Mar 2019 from EV-201 (NCT03219333) Cohort 1 (C1) showing an ORR of 44% and a manageable side effect profile. We present data on C1 OS and safety with an additional year of follow-up (fu). Methods: Pts in this open-label, multicenter study received EV 1.25 mg/kg on Days 1, 8, 15 of each 28-day cycle. The primary endpoint was confirmed ORR per RECIST 1.1 by BICR. Key secondary endpoints were OS, safety/tolerability, duration of response, and PFS. Results: 125 pts received EV in C1 (md age 69 y; md 3 prior systemic therapies; 35% upper tract disease; 40% liver metastases). Md fu was 22.3 mo (range, 0.5-27.3+) and md OS was 12.4 mo (95% CI: 9.46, 15.57). OS rates at 12 and 18 mo were 50.4% and 34.2%, respectively. Md and maximum treatment (tx) duration were 4.6 mo and 27.3 mo (ongoing as of data cutoff), respectively. The most common tx-related AEs included alopecia (49.6%), fatigue (49.6%), and decreased appetite (44%). Tx-related AEs of interest included any skin reactions (51.2% all grade [AG], 12.8% ≥ G3), any peripheral neuropathy (50.4% AG, 3.2% ≥ G3), and any hyperglycemia (11.2% AG, 5.6% ≥ G3). Conclusions: OS from long-term fu of la/mUC pts who previously received PD-1/PD-L1-i and Pt-CC in EV-201 C1 is encouraging, with half of the pts alive at 12 mo and one-third alive at 18 mo; the safety of EV continues to be manageable in these pts with no new signals. Clinical trial identification: NCT03219333. Editorial acknowledgement: Medical writing assistance was funded by Seattle Genetics, Inc., and provided by Andrea Gwosdow, Ph.D. of Biobridges. Legal entity responsible for the study: Seattle Genetics and Astellas Pharma, Inc. Funding: Seattle Genetics and Astellas Pharma, Inc. Disclosure: P. O'Donnell: Honoraria (institution): Astellas; Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): Genentech; Honoraria (institution): Harrison Consulting Group; Honoraria (institution): Inovio; Honoraria (institution), Research grant/Funding (institution): Janssen; Honoraria (institution): Kantar Health; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (institution): OncLive; Honoraria (institution): Parexel; Honoraria (institution): Quintiles; Honoraria (institution), Research grant/Funding (institution): SeaGen; Research grant/Funding (institution): Acerta; Research grant/Funding (institution): B-M Squibb; Shareholder/Stockholder/Stock options: Allergan; Shareholder/Stockholder/Stock options: PrescriptlQ. M.D. Galsky: Advisory/Consultancy: Aileron Therapeutics; Advisory/Consultancy: Astellas; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: BioMotiv; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Dendreon; Advisory/Consultancy: Dracen; Advisory/Consultancy: EMD Serono; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Incyte; Advisory/Consultancy: Inovio Pharma; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: NuMab; Advisory/Consultancy: Pfizer; Advisory/Consultancy: SeaGen; Shareholder/Stockholder/Stock options: Rappta Therapeutics; Licensing/Royalties, July 2012 Application Number 20120322792: Mount Sinai School of Medicine. J.E. Rosenberg: Honoraria (self), Travel/Accommodation/Expenses: Chugai; Advisory/Consultancy: Adicet Bio; Advisory/Consultancy: Agensys; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: BioClin Therapeutics; Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Fortress Biotech; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Inovio Pharma; Advisory/Consultancy: Janssen; Advisory/Consultancy: Lilly; Advisory/Consultancy: Merck; Advisory/Consultancy: Pharmacyclics; Advisory/Consultancy, Research grant/Funding (institution): QED Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/Genentech; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy: Sensei Biotherapeutics; Advisory/Consultancy: Western Oncolytics; Advisory/Consultancy: Boerhinger Ingelheim; Advisory/Consultancy: Pfizer; Advisory/Consultancy: MedImmune; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Jounce Therapeutics; Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): Novartis; Licensing/Royalties: Predictor of Platinum Sensitivity. D.P. Petrylak: Advisory/Consultancy, Research grant/Funding (institution): Ada Cap (Advanced Accelerator Applications); Advisory/Consultancy, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Research grant/Funding (institution): Agensys Inc; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Bicycle Therapeutics; Advisory/Consultancy: Boehringer Ingelheim; Research grant/Funding (institution): BioXcel Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy: Exelixis; Research grant/Funding (institution): Endocyte; Advisory/Consultancy: Incyte; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Innocrin; Advisory/Consultancy: Janssen; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Medivation; Advisory/Consultancy, Research grant/Funding (institution): Mirati; Advisory/Consultancy: Monopteros; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Pharmacyclics; Research grant/Funding (institution): Progenics; Research grant/Funding (institution): Replimune; Advisory/Consultancy, Research grant/Funding (institution): Roche; Research grant/Funding (institution): Sanofi Aventis; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy: Urogen; Shareholder/Stockholder/Stock options: Bellicum; Shareholder/Stockholder/Stock options: Tyme. A.V. Balar: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca/Medimmune; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genentech/Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Cerulean Pharma; Advisory/Consultancy: Incyte; Advisory/Consultancy: Nektar; Advisory/Consultancy: Pfizer/EMD Serano; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Shareholder/Stockholder/Stock options: Epivax Oncology. B.A. McGregor: Advisory/Consultancy: Astelleas; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: Janssen; Advisory/Consultancy: Nextar; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (institution): SeaGen; Advisory/Consultancy: EMD.Eisai; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Calithera Biosciences. E. Heath: Honoraria (institution): Bayer; Honoraria (institution): Dendreon; Honoraria (institution): Sanofi; Honoraria (institution), Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy: Agensys; Speaker Bureau/Expert testimony: Sanofi; Research grant/Funding (institution): Agensys; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): B-M Squibb; Research grant/Funding (institution): Caris; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Celldex; Research grant/Funding (institution): Corcept; Research grant/Funding (institution): Curemeta; Research grant/Funding (institution): Dendreon; Research grant/Funding (institution): eFFECTOR Thera; Research grant/Funding (institution): Esanik; Research grant/Funding (institution): Fortis; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): GSK;