1. 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.

2. 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: Spira AI, et al. ASCO Abstract 8010.

3. 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 Abstract 8010.

4. 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 Abstract 8010.

5. 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 ( )
.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 ( )
0.63 ( )
0.56 ( )
0.46 ( )
.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 Abstract 8010.

6. 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 Abstract 8010.

7. 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 Abstract 8010.

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