POPLAR: Atezolizumab Improved Survival vs Docetaxel in Patients With Advanced NSCLC and Increasing Levels of PD-L1 Expression 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. NSCLC, non-small-cell lung cancer. This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

POPLAR: Background NSCLC characterized by high mutation rates[1] Potentially increased immunogenicity and attack by immune-infiltrating tumor cells, provided immune responses are not dampened by immune checkpoints Atezolizumab (formerly MPDL3280A): humanized anti–PD-L1 antibody that inhibits the PD-1 immune checkpoint pathway Blocks PD-L1 interactions with PD-1/B7.1, restoring antitumor T-cell activity and boosting T-cell priming PD-L1 expression on tumor cells (TC) and immune cells (IC) by IHC assay (SP142 antibody) potentially predictive of atezolizumab activity POPLAR: randomized phase II study of atezolizumab vs docetaxel in pts with advanced NSCLC who failed prior platinum-based chemotherapy[2] IHC, immunohistochemistry; NSCLC, non-small-cell lung cancer. 1. Chen DS, et al. Clin Cancer Res. 2012;18:6580-6587. 2. Spira AI, et al. ASCO 2015. Abstract 8010.

POPLAR: Atezolizumab vs Docetaxel in Previously Treated NSCLC Pts with locally advanced or metastatic NSCLC and ECOG PS 0-1 who failed prior platinum-containing chemotherapy (N = 287) Atezolizumab 1200 mg IV q3w (n = 144) Docetaxel 75 mg/m2 IV q3w (n = 143) Stratified by PD-L1 immune cell expression (0 vs 1 vs 2 vs 3), histology (squamous vs nonsquamous), and line of therapy (second vs third line) DoR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; ITT, intent to treat; IV, intravenous; NSCLC, non-small-cell lung cancer; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; q3w, every 3 weeks. Primary endpoint: OS in PD-L1–selected and ITT populations Secondary endpoints: overall safety as well as PFS, ORR, DoR in PD-L1– selected and ITT populations Spira AI, et al. ASCO 2015. Abstract 8010.

POPLAR: Baseline Characteristics Atezolizumab (n = 144) Docetaxel (n = 143) Median age, yrs 62 Male, % 65 53 Nonsquamous histology, % 66 ECOG PS 1, % 67 68 Prior maintenance therapy, % 42 38 1 prior systemic chemotherapy regimen, % History of tobacco use, % Never Current Previous 19 17 64 20 15 ECOG PS, Eastern Cooperative Oncology Group performance status. Spira AI, et al. ASCO 2015. Abstract 8010.

POPLAR: Efficacy of Atezolizumab Increased With Higher PD-L1 Expression Interim Median OS Outcomes Atezolizumab (n = 144) Docetaxel (n = 143) HR (95% CI) P Value ITT population (N = 287) 11.4 9.5 0.77 (0.55-1.06) .11 Subgroups based on PD-L1 expression* TC0 and IC0 (n = 92) TC1/2/3 or IC1/2/3 (n = 195) TC2/3 or IC2/3 (n = 105) TC3 or IC3 (n = 47) 9.7 NR 13.0 9.1 7.4 11.1 1.12 (0.64-1.93) 0.63 (0.42-0.94) 0.56 (0.33-0.94) 0.46 (0.19-1.09) .70 .024 .026 .070 *PD-L1 expression measured by SP142 IHC assay (low expression – TC0/IC0, high expression - TC3/IC3). PFS and ORR: similar trends in outcome for atezolizumab vs docetaxel based on PD-L1 expression Median PFS in ITT population: 2.8 vs 3.4 mos (HR: 0.98) Median PFS in TC3 or IC3 population: 7.8 vs 3.9 mos (HR: 0.57) ORR in ITT population: 15% vs 15% ORR in TC3 or IC3 population: 38% vs 13% Interim data based on minimum of 10 mos of follow-up IC, immune cell; IHC, immunohistochemistry; ITT, intent to treat; NR, not reached; ORR, overall response rate; OS, overall survival; PD-L1, programmed death ligand 1; PFS, progression-free survival; TC, tumor cell. Spira AI, et al. ASCO 2015. Abstract 8010.

POPLAR: Safety Profile Safety Outcome Atezolizumab (n = 142) Docetaxel (n = 135) Median treatment duration, mos 3.7 2.1 Treatment-related AEs, % 67 88 Treatment-related grade 3/4 AEs, % 12 39 All-cause grade 5 AEs, % 4 Treatment discontinuation due to AEs, % 8 22 AEs: consistent with prior studies Incidence of individual immune-related AEs ≤ 4% for atezolizumab AEs (all grades) occurring with ≥ 5% difference between arms Increased incidence in atezolizumab arm: decreased appetite, dyspnea, arthralgia, insomnia, musculoskeletal pain, pneumonia, hypothyroidism Increased incidence in docetaxel arm: alopecia, nausea, diarrhea, anemia, asthenia, myalgia, neutropenia, peripheral neuropathy, febrile neutropenia, peripheral sensory neuropathy AEs, adverse events. Spira AI, et al. ASCO 2015. Abstract 8010.

POPLAR: Conclusions Atezolizumab demonstrated pattern of improved survival Clinical outcomes correlated with PD-L1 expression in NSCLC In TC3 or IC3 tumors (highest PD-L1 expression), OS HR: 0.46 In TC0 and IC0 tumors (< 1% PD-L1 expression), OS HR: 1.12 In ITT population (all levels of PD-L1 expression), OS HR: 0.77 IHC SP142 assay Sensitive and specific, measures PD-L1 expression on both TC and IC, predictive diagnostic biomarker for atezolizumab in NSCLC Toxicity reduced in atezolizumab arm vs docetaxel; AE profile consistent with previous studies AE, adverse event; IC, immune cell; IHC, immunohistochemistry; NSCLC, non-small-cell lung cancer; OS, overall survival; PFS, progression-free survival; TC, tumor cell. Spira AI, et al. ASCO 2015. Abstract 8010.

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