Abstract 746P
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; Research grant/Funding (institution): Ignyta; Research grant/Funding (institution): Inovio Pharma; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Oncolys; Research grant/Funding (institution): Plexxikon; Research grant/Funding (institution): Synta; Research grant/Funding (institution): Tokai Pharma; Research grant/Funding (institution): Zenith Epigenetics. E.Y. Yu: Advisory/Consultancy: Abbvie; Advisory/Consultancy: Advanced Accelerator Applications; Advisory/Consultancy: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Clovis; Advisory/Consultancy: Dendreon; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Incyte; Advisory/Consultancy: Janssen; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy: Sanofi-Genzyme; Advisory/Consultancy, Research grant/Funding (institution): SeaGen; Advisory/Consultancy: Tolmar; Research grant/Funding (institution): Daiichi-Sankyo; Research grant/Funding (institution): Dendreon; Research grant/Funding (institution): Pharmacyclics; Research grant/Funding (institution): Taiho. D.I. Quinn: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Seattle Genetics; Full/Part-time employment: USC. N.M. Hahn: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: Health Advances; Advisory/Consultancy: Inovio Pharma; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Oncogenex; Advisory/Consultancy: Pieris Pharma; Research grant/Funding (institution): Acerta Pharma; Research grant/Funding (institution): Heat Biologics; Research grant/Funding (institution): Mirati Therapeutics; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Principa Biopharma. M. Campbell: Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics, Inc. S-Y. Liang: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics. J. Steinberg: Travel/Accommodation/Expenses, Full/Part-time employment: Astellas Pharma. Y. Loriot: Honoraria (institution), Research grant/Funding (institution): Roche; Honoraria (institution), Research grant/Funding (institution): Astellas; Honoraria (institution), Research grant/Funding (institution): Janssen; Honoraria (institution), Research grant/Funding (institution): Seattle Genetics; Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): BMS; Honoraria (institution), Research grant/Funding (institution): MSD; Honoraria (institution), Research grant/Funding (institution): Pfizer; Honoraria (institution), Research grant/Funding (institution): Sanofi; Honoraria (institution): Ipsen; Research grant/Funding (institution): Clouis; Research grant/Funding (institution): Incyte.