NCI/CTEP 7435: Eribulin Active, Tolerable in Urothelial Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting* May 29 - June 2, 2015 *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

Eribulin: Novel Tubulin Inhibitor Need for new agents in advanced urothelial cancer Erubulin: a novel tubulin inhibitor that promotes mesenchymal to epithelial transformation Demonstrated efficacy in phase III trials in breast cancer, soft tissue sarcoma[1,2] Promising results from single-arm phase I and II trials of eribulin in pts with advanced urothelial cancer, in the first- and second-line settings Current report on composite results from a single phase II trial in advanced urothelial cancer[3] 1. Cortes J, et al. Lancet. 2011;377:914-923. 2. Schöffski P, et al. ASCO 2015. Abstract LBA10502. 3. Quinn DI, et al. ASCO 2015. Abstract 4504.

NCI/CTEP 7435: Eribulin in Advanced Urothelial Carcinoma A multicenter, single-arm phase II trial Primary endpoint: ORR ≥ 20% Secondary endpoints: PFS, 6-mo PFS, OS, toxicity Stratified by prior exposure to tubulin inhibitor Pts with measureable locally advanced or metastatic urothelial cancer; either untreated or ≤ 2 lines previous therapy (at least 1 platinum-based) (N = 150) Eribulin 1.4 mg/m2 IV Days 1, 8 of 21-day cycle IV, intravenous; ORR, overall response rate; OS, overall survival; PFS, progression-free survival. Quinn DI, et al. ASCO 2015. Abstract 4504.

NCI/CTEP 7435: Baseline Characteristics Pts (N = 150) Median age, yrs (range) 67 (37-90) Male, % 70.7 Race (white/Asian/black/other), % 81/13/2/5 Lower tract as primary site, % 89 Urothelial histology (transitional cell cancer), % 90 Median creatinine clearance, mL/min (range) 56.7 (15.9-276) Renal dysfunction (normal/moderate/severe), % 81/11/8 Visceral metastases, % 69.3 Liver metastases, % 29.3 Quinn DI, et al. ASCO 2015. Abstract 4504.

NCI/CTEP 7435: Baseline Risk Characteristics Pts (N = 150) Karnofsky PS < 90, % 43 MSK Bajorin risk group, % 1 2 29 60 11 Bellmunt risk group, % 3 7.3 36.0 48.0 8.7 MSK, Memorial Sloan Kettering; PS, performance status. Quinn DI, et al. ASCO 2015. Abstract 4504.

NCI/CTEP 7435: Eribulin Shows Promising Activity Across All Cohorts Outcome All (N = 150) First Line (n = 52) Second Line, Tubulin Naive (n = 53) Tubulin Exp (n = 45) ORR (CR + PR), % 34.7 46.2 30.1 26.7 SD, % 38.7 38.5 43.4 33.3 Median duration of SD, wks (range) 12 (5-102) 12 (5-43) 12 (6-102) 18 (6-30) Median OS, mos 9.5 11.3 9.7 8.4 Median PFS, mos 4.1 4.2 3.9 CR, complete response; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; SD, stable disease. Bellmunt, Bajorin risk stratification methods predict PFS, OS in this cohort Bellmunt classification may be superior as OS predictor; time from last chemotherapy may add information for stratification Quinn DI, et al. ASCO 2015. Abstract 4504.

NCI/CTEP 7435: Safety Select AEs of Interest, % Overall (N = 150) Grade 1 Grade 2 Grade 3 Grade 4 Anemia 38 29 13 Neutropenia 6 15 21 35 Febrile neutropenia 4 Anorexia 10 1 Sensory neuropathy* 33 11 ALT increase 25 5 AST increase 2 AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase. No difference between tubulin-naive, -exposed patients Older than 70 yrs of age associated with increased risk of grade 3 ≥ AEs, including neutropenia *18% of pts initiated study with grade 1 neuropathy. Quinn DI, et al. ASCO 2015. Abstract 4504.

NCI/CTEP 7435: Conclusions Eribulin active in both untreated and previously treated advanced urothelial carcinoma ORR exceeded prespecified 20% boundary for further evaluation No difference in OS or PFS among cohorts Tolerable toxicity, with neutropenia and anemia most common ≥ grade 3 AEs Pts with mild to moderate renal impairment can receive full dosing Phase III trial comparing eribulin to platinum-containing regimens in advanced urothelial cancer planned AE, adverse event; ORR, overall response rate; OS, overall survival; PFS, progression-free survival. Quinn DI, et al. ASCO 2015. Abstract 4504.

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