IMvigor 210 (Cohort 1): First-line Atezolizumab in Cisplatin-Ineligible Metastatic Urothelial Carcinoma CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016 *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 activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

IMvigor 210 (Cohort 1): Background Cisplatin the is first-line standard of care for metastatic urothelial carcinoma Most pts are cisplatin ineligible due to poor performance status, impaired renal function, or comorbidities[1] Non-cisplatin–based regimens associated with short response duration, lack of survival benefit, high discontinuation rate[2] Atezolizumab: engineered mAb targeting PD-L1 immune checkpoint Active, well tolerated in treatment-experienced mUC[3] Currently FDA approved only in cisplatin-treated pts Cohort 1 of the IMvigor 210 study evaluated safety, efficacy of atezolizumab as first-line therapy in untreated, cisplatin-ineligible mUC pts[4] mAb, monoclonal antibody; mUC, metastatic urothelial carcinoma. 1. Galasky MD. ECC 2015. Abstract 2624. 2. De Santis M, et al. J Clin Oncol. 2012;30:191-199. 3. Rosenberg JE, et al. Lancet. 2016;387:1909-1920. 4. Balar AV, et al. ASCO 2016. Abstract LBA4500. Slide credit: clinicaloptions.com

cisplatin ineligible* IMvigor 210: Study Design Single-arm phase II study with 2 cohorts[1] Pts with inoperable advanced or metastatic UC, predominantly TCC histology, evaluable tumor tissue for PD-L1 testing (N = 429) Cohort 1: (n = 119)[2] previously untreated, cisplatin ineligible* Atezolizumab 1200 mg IV Q3W until PD Cohort 2: (n = 310)[3] prior platinum treatment Atezolizumab 1200 mg IV Q3W until loss of benefit DoR, duration of response; ECOG PS, Eastern Cooperative Oncology Group; eGFRCG, estimated Glomerular Filtration Rate Cockcroft-Gault; mUC, metastatic urothelial carcinoma; ORR, objective response rate; PD, progressive disease; PS, performance status; RECIST, Response Evaluation Criteria in Solid Tumors; TCC, transitional cell carcinoma. *≥ 1 of the following: ECOG PS 2; grade ≥ 2 hearing loss or peripheral neuropathy; renal impairment (eGFRCG: > 30, < 60 mL/min). Cohort 1 study Primary endpoint: confirmed ORR by RECIST v1.1 (per central, independent review) Secondary endpoints: DoR, PFS, OS, safety 1. ClinicalTrials.gov. NCT02108652. 2. Balar AV, et al. ASCO 2016. Abstract LBA4500. 3. Dreicer R, et al. ASCO 2016. Abstract 4515. Slide credit: clinicaloptions.com

IMvigor 210 (Cohort 1): Pt Characteristics Characteristics consistent across PD-L1 IC subgroups Characteristic Cisplatin-Ineligible mUC (N = 119) Median age, yrs (range) 80 yrs or older, % 73 (51-92) 21 Male, % 81 PD-L1 status on immune cells: IC0/IC1/IC2/3, % 33/40/27 Metastatic disease, % Visceral sites 92 66 Cisplatin ineligibility criteria, % Renal impairment (eGFRCG: > 30, < 60 mL/min) Hearing loss (25 dB) Peripheral neuropathy (grade ≥ 2) ECOG PS 2 70 14 6 20 ECOG, Eastern Cooperative Oncology Group; eGFRCG, estimated Glomerular Filtration Rate Cockcroft-Gault; IC, immune cell; mUC, metastatic urothelial carcinoma; PS, performance status. Slide credit: clinicaloptions.com Balar AV, et al. ASCO 2016. Abstract LBA4500.

IMvigor 210 (Cohort 1): Response Outcome IC0 (n = 39) IC1 (n = 48) IC2/3 (n = 32) All Pts (N = 119) ORR,* % CR PR 21 8 13 23 6 17 28 22 24 7 Median time to response,† mos 2.0 (1.8-6.0) 2.4 (1.8-4.8) 2.1 (2.0-4.1) -- Reduced tumor burden, % 63 (n = 30) 51 65 (n = 26) 59 (n = 95) *19 pts with missing/unevaluable responses included in ORR analysis. †Responders only. DoR, duration of response; IC, immune cell; ORR, objective response rate. Median DoR not reached in any PD-L1 IC subgroup Responses seen in all analyzed subgroups including poor baseline prognostic factors, pts 80 yrs of age or older ORR similar for all cisplatin-ineligible criteria subgroups Slide credit: clinicaloptions.com Balar AV, et al. ASCO 2016. Abstract LBA4500.

IMvigor 210 (Cohort 1): Change in Tumor Burden 59% of all evaluable pts had decreased target lesions Median follow- up: 14.4 mos (range, 0.2-20.1) 100 IC2/3; 28% ORR 17/26 (65%) -100 100 IC1; 23% ORR Maximum SLD Reduction From Baseline, % 20/39 (51%) RECIST v1.1 Response -100 IC, immune cell; RECIST, Response Evaluation Criteria in Solid Tumors; SLD, sum of the longest diameter. PD SD PR CR 100 IC0; 21% ORR -100 19/30 (63%) Balar AV, et al. ASCO 2016. Abstract LBA4500. Reproduced with permission. Slide credit: clinicaloptions.com

IMvigor 210 (Cohort 1): OS OS by PD-L1 Status[1] 100 Subgroup mOS (95% CI) All (N = 119) IC0/1 (n = 87) IC2/3 (n = 32) 14.8 mo (10.1-NE) 15.3 mo (9.8-NE) 12.3 mo (6.0-NE) 80 60 Overall Survival, % 12-mo OS rate: 57% (95% CI: 48-66) 40 20 2 4 6 8 10 12 14 16 18 20 Time, mos IC, immune cell; NE, not estimable; mOS, median overall survival; IC, immune cell. Favorable preliminary survival outcomes vs historic data from non-cisplatin regimens[2,3] Survival similar in all PD-L1 IC subgroups 98 pts discontinued 26 pts went on to receive subsequent therapy postprotocol 1. Balar AV, et al. ASCO 2016. Abstract LBA4500. Reproduced with permission. 2. De Santis M, et al. J Clin Oncol. 2012;30:191-199. 3. Galsky MD, et al. ECC 2015. Abstract 2624. Slide credit: clinicaloptions.com

IMvigor 210 (Cohort 1): Safety AE, % (N = 119) Any Cause Treatment Related Any AE 96 66 Serious AE 36 8 Grade 3/4 45 15 Grade 5 3 1 35% had AE leading to dose interruption; 6% leading to treatment withdrawal Most treatment-related AEs grade 1/2; only a single treatment- related grade 5 AE (sepsis) No decline in renal function in pts with prior renal impairment 6% had grade 3/4 immune-related AE requiring steroids AE, adverse event. Slide credit: clinicaloptions.com Balar AV, et al. ASCO 2016. Abstract LBA4500.

IMvigor 210 (Cohort 1): Treatment- and Immune-Related AEs Treatment-Related AEs in ≥ 5% of Pts, % (N = 119) All Grades Grade 3/4 Fatigue 30 3 Diarrhea 11 1 Pruritus Anorexia 9 Hypothyroidism 6 Anemia 5 Chills Nausea Pyrexia Rash Vomiting Immune-Related AEs,* % (N = 119) All Grades Grade 3/4 Rash 3 1 Pruritus ALT ↑ 2 Serum bilirubin ↑ Rhabdomyolysis AST increased Autoimmune colitis Colitis Hyperglycemia Liver disorder AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase. *Requiring systemic corticosteroids. Slide credit: clinicaloptions.com Balar AV, et al. ASCO 2016. Abstract LBA4500.

IMvigor 210 (Cohort 1): Conclusions Rapid and durable responses to atezolizumab in previously untreated cisplatin-ineligible mUC Responses seen in all PD-L1 IC subgroups 75% (21/28) responses ongoing after data cutoff Early survival data favorable in all PD-L1 IC subgroups Well-tolerated safety profile with few treatment-related grade ≥ 3 AEs Investigators suggest atezolizumab has potential as new standard-of-care therapy in cisplatin-ineligible pts, pending further investigation AE, adverse event; IC, immune cell; mUC, metastatic urothelial carcinoma. Slide credit: clinicaloptions.com Balar AV, et al. ASCO 2016. Abstract LBA4500.

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