1. Lancet Oncol 2016;17(11):
Updated Results from KEYNOTE-021 Cohort G: A Randomized, Phase 2 Study of Pemetrexed and Carboplatin (PC) with or without Pembrolizumab (pembro) as First-Line Therapy for Advanced Nonsquamous NSCLC
Borghaei H et al. Proc ESMO 2017;Abstract LBA49.

2. KEYNOTE-021 Cohort G: Response Rates and Updated Survival Analyses
HR = 0.59 p = 0.03
Endpoint
Pembro + PC (n = 60)
PC alone (n = 63) HR
p-value
ORR
56.7%
31.7% —
0.0029
mPFS
19.0 mo
8.9 mo
0.54
0.0067
mOS
Not reached
20.9 mo
0.59
0.03
Borghaei H et al. Proc ESMO 2017;Abstract LBA49.

3. KEYNOTE-189 Phase III Trial Design
Pembrolizumab 200 mg + pemetrexed 500 mg/m2 + (cisplatin 75 mg/m2 or carboplatin AUC 5)
q3wk x 4 cycles*
Estimated accrual (n = 646)
Stage IV nonsquamous NSCLC
No sensitizing EGFR mutation or ALK translocation
Treatment naïve R
Placebo + pemetrexed 500 mg/m2 + (cisplatin 75 mg/m2 or carboplatin AUC 5)
q3wk x 4 cycles†
2:1
* Followed by pembrolizumab 200 mg with pemetrexed 500 mg/m2 q3wk until disease progression
† Followed by placebo with pemetrexed 500 mg/m2 q3wk until disease progression
Press release: Significant improvement in overall and progression-free survival in the first-line setting with pembrolizumab plus chemotherapy versus chemotherapy alone
NCT

4. Love N et al. Proc IASLC 2017;Abstract 75.
A Biomarker-Driven Algorithm for Sequencing of Systemic Therapy for Metastatic Non-Small Cell Lung Cancer: A Survey of 25 Investigators
Love N et al. Proc IASLC 2017;Abstract 75.

5. Love N et al. Proc IASLC 2017;Abstract 75.
TPS = PD-L1 tumor proportion score
Low TPS = 10%; high TPS = 60%
Low TPS
High TPS
No targetable mutation
EGFR mutation
ALK rearrangement
ROS1 rearrangement
BRAF V600E mutation
MET exon 14 mutation
RET rearrangement
HER2 mutation
The New Taxonomy of Metastatic Non-Small Cell Lung Cancer
T790M mutation-positive
T790M mutation-negative
Nonsquamous
Squamous (no targetable mutation)
 Targeted treatment
Chemotherapy ± biologic
Chemotherapy + checkpoint inhibitor
Checkpoint inhibitor
Love N et al. Proc IASLC 2017;Abstract 75. 

6. First-Line Treatment for Metastatic Squamous NSCLC
Survey of clinical investigators (n = 25)
TPS 10%
Carboplatin/nab paclitaxel
TPS 60%
Love N et al. Proc IASLC 2017;Abstract 75. 

7. First-Line Treatment for Metastatic Nonsquamous NSCLC and No Identified Targetable Mutation
Survey of clinical investigators (n = 25)
TPS 10%
TPS 60%
Love N et al. Proc IASLC 2017;Abstract 75. 

8. Re-treated pts with irAE Re-treated pts without irAE
Safety of Re-treatment with Immunotherapy After Immune-Related Toxicity in Patients with Lung Cancer Treated with Anti-PD-1/PD-L1 Therapy
MSKCC cohort: Recurrent or new irAEs in re-treated patients Number of patients re-treated after a serious irAE (n = 38)
Number of patients with new or recurrent irAE (n = 19)
n (%)
Re-treated pts with irAE
24% recurrent/26% new
Re-treated pts without irAE
p-value
Grade of initial irAE
1/2 vs 3/4
12 (50) vs 7 (50)
1.0
Hospitalization for initial irAE
7 (87)
1 (13)
0.02
Steroid taper >4 weeks
7 (70)
3 (30)
0.15
Time to initial irAE
<3 months
>3 months
15 (63)
4 (29)
9 (37)
10 (71)
0.04
Deaths (due to irAE)   in re-treated pts
2/38 (5%)
Objective response
3/38 (8%)
irAE after re-treatment by initial irAE, n/N (%)
Re-treated pts
Arthralgia or myalgia
4/5 (80)
Colitis
4/7 (57)
Rash
2/5 (40)
Pneumonitis
2/6 (33)
Santini FC, ASCO 2017;Abstract 9012.

9. Immunotherapy Re-treatment OS/PFS
PFS, OS similar in re-treated vs discontinued cohorts among pts who achieved CR/PR before initial irAE OS
PFS
P = 0.9
P = 0.31
Months
Probability of PFS
Probability of OS
0.25
0.50
0.75
1.00 10 20 30
Retreated
Discontinued 40
Santini FC, ASCO 2017;Abstract 9012.

10. PACIFIC: Phase III Trial of Durvalumab After Chemoradiation Therapy in Stage III, Locally Advanced, Unresectable NSCLC
Durvalumab 10 mg/kg q2wk for up to 12 months N = 476
Coprimary endpoints
PFS by BICR using RECIST v1.1
Overall survival
Stage III, locally advanced, unresectable NSCLC with no disease progression after definitive platinum-based cCRT (≥2 cycles)
18 years or older
WHO PS 0 or 1
Estimated life expectancy of
≥12 weeks
Archived tissue
All-comers population
1-42 days post-cCRT
2:1 randomization, stratified by age, sex and smoking history N = 713
Key secondary endpoints
ORR (per BICR)
DoR (per BICR)
Safety and tolerability
Patient-reported outcomes
Placebo 10 mg/kg q2wk for up to 12 months N = 237
cCRT = concurrent chemoradiation therapy; BICR = blinded independent central review
Paz-Ares L et al. Proc ESMO 2017;Abstract LBA1.

11. PACIFIC: Progression-Free Survival (by BICR)
Stratified hazard ratio, 0.52
Two-sided p < 0.001
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Durvalumab
(N = 476)
Placebo
(N = 237)
Median PFS, months
16.8
5.6
12-month PFS rate
55.9%
35.3%
18-month PFS rate
44.2%
27.0%
PFS probability
Durvalumab
Placebo 3 6 9 12 15 18 21 24 27
Time from randomization (months)
Paz-Ares L et al. Proc ESMO 2017;Abstract LBA1; Antonia SJ et al. N Engl J Med 2017;377(20):

12. SQUIRE Trial: Phase III Study Design
Gem-Cis + Neci q3w (N = 545)
Necitumumab (800 mg D1, D8)
Gemcitabine (1,250 mg/m², D1, D8)
Cisplatin (75 mg/m², D1)
Neci q3w
(800 mg D1, D8) PD
PRCRSD
Maximum of 6 cycles
Screening
Entry criteria: Stage IV squamous NSCLC1,2
ECOG PS 0-2 1 R
Gem-Cis q3w (N = 548)
Gemcitabine (1,250 mg/m², D1, D8)
Cisplatin (75 mg/m², D1) 1
Randomization (R) stratified by ECOG PS (0-1 vs 2) and geographic region (North America, Europe and Australia vs South America, South Africa and India vs Eastern Asia)
Primary Endpoint: Overall survival (OS)
Secondary Endpoints: Response rate, PFS, safety and other
Exploratory Endpoints: Correlation with EGFR expression (H-score) and other
1 AJCC TNM Classification, 7th edition, 2009; 2 UICC TNM Classification of Malignant Tumors, 7th edition, 2009
Thatcher N et al, Lancet Oncology 2015;16(7):

13. SQUIRE Trial: Overall SurvivalOS
Nec + Gem + Cis (n = 545)
Gem + Cis (n = 548)
HR, p-value
Median OS
1-y OS
2-y OS
11.5 mo
48%
20%
9.9 mo
43%
17%
0.84, 0.01
Deaths
418 (77%)
442 (81%)
Thatcher N et al. Lancet Oncology 2015;16(7):

14. SQUIRE Trial: Secondary Endpoints and Safety
Gem/Cis + Neci  (n = 545)
Gem/Cis  (n = 548)
ORR (CR + PR)
31%
29%
p = 0.40
DCR
82%
77%
p = 0.043
Median PFS
5.7 mo
5.5 mo
HR: 0.85
( )
p = 0.020
Safety
Higher rate of serious adverse events in Gem/Cis + Neci arm: 38% vs 48%
Slightly higher rate of AEs leading to discontinuation in Gem/Cis + Neci arm: 25% vs 31%
Low rate of treatment-related fatal adverse events: 2% vs 3%
Main differential adverse events in Gem/Cis + Neci arm: rash, hypomagnesemia, venous thromboembolic events
Thatcher N et al. Lancet Oncology 2015;16(7):

15. REVEL Trial: Phase III Study Design
Ramucirumab 10 mg/kg +
Docetaxel 75 mg/m2 q3wk
N = 628
Stage IV NSCLC after 1 platinum-based chemo +/- maintenance
Prior Bev allowed
All histologies
ECOG PS 0 or 1
Treatment until disease progression
or unacceptable toxicity R
Placebo +
Docetaxel 75 mg/m2 q3wk
N = 625
1:1
Stratification factors:
ECOG PS 0 vs 1
Gender
Prior maintenance
East Asia vs ROW
Primary endpoint: Overall survival
Secondary endpoints: PFS, ORR, safety, patient-reported outcomes using the Lung Cancer Symptoms Scale (LCSS)
Bev = bevacizumab; ORR = objective response rate; PFS = progression-free survival; ROW = rest of the world
Garon EB et al; Lancet 2014;384(9944):665-73

16. OS by Histology
Median overall survival
Ramucirumab
+ docetaxel
Placebo + docetaxel
Hazard ratio
p-value
All patients (n = 628, 625)
10.5 mo
9.1 mo
0.86
0.023
Nonsquamous (n = 465, 447)
11.1 mo
9.7 mo
0.83
0.020
Squamous (n = 157, 171)
9.5 mo
8.2 mo
0.88
0.319
Most subgroups had numerically longer survival on the ramucirumab arm.
Garon EB et al; Lancet 2014;384(9944):

17. REVEL: PFS and RR in ITT and SCC
Ramucirumab + docetaxel
Placebo + docetaxel
Hazard ratio
(95% CI)
p-value
Median PFS
ITT (n = 628, 625) SCC (n = 157, 171)
4.5 mo 4.2 mo
3.0 mo 2.7 mo
0.76 ( ) ( )
<
ORR
ITT (n = 628, 625) SCC (n = 157, 171)
22.9% 26.8%
13.6% 10.5%
— —
<0.001 <0.001
DCR
ITT (n = 628, 625) SCC (n = 157, 171)
64.0% 59.9%
52.6% 45.0%
<
Garon EB et al; Lancet 2014;384(9944):

18. Oxnard G et al. Plasma genotyping for predicting benefit from osimertinib in patients (pts) with advanced NSCLC. Proc ESMO 2016;Abstract 135O_PR.

19. Association between Plasma Genotyping and Outcomes with Osimertinib
Sensitivity of plasma genotyping for detection of EGFR mutations:
T790M: 70%
Exon 19 del: 82%
Exon 21 L858R: 86%
Plasma positive for T790M in 31% of cases negative for T790M in tumor
Outcome
Tumor
T790M +
T790M -
Plasma
ORR (n = 173, 58, 164, 102)
62%
26%
63%
46%
Median PFS (n = 179, 58, 169, 104)
9.7 mo
3.4 mo
8.2 mo
Oxnard GT et al. J Clin Oncol 2016;34(28):
Oxnard GT et al. Proc ESMO 2016;Abstract 135O_PR.

20. Wakelee HA et al. Proc ASCO 2016;Abstract 9001.
Epidermal Growth Factor Receptor (EGFR) Genotyping of Matched Urine, Plasma and Tumor Tissue from Non-Small Cell Lung Cancer (NSCLC) Patients (Pts) Treated with Rociletinib
Wakelee HA et al. Proc ASCO 2016;Abstract 9001.

21. Plasma and Urine Detection Is Sensitive and Complements Tissue T790M Testing
Tissue as reference, plasma sensitivity = 80.9% (313/387)
Plasma vs tissue
T790M
Tissue
Total
Positive
Negative
Inadequate
Plasma (BEAMing)
313 23 38
374 74 17
108
387 40 55
482
Urine sensitivity = 81.1% (142/175), with tissue as a reference
Tissue as reference, urine sensitivity = 81.1% (142/175)
Urine vs tissue
T790M
Tissue
Total
Positive
Negative
Inadequate
Urine
142 11 16
169 31 5 6 42 2
175 22
213
Wakelee HA et al. Proc ASCO 2016;Abstract 9001.

22. Plasma, Tissue and Urine Identify Unique and Overlapping Subsets of Patients with T790M Mutation-Positive Disease
181 samples had matched pretreatment T790M results in plasma, tissue and urine
57% were positive by all 3 sample types
Wakelee HA et al. Proc ASCO 2016;Abstract 9001.

23. Drilon A et al. Lancet Oncol 2016;17(12):1653-60.
Cabozantinib in Patients with Advanced RET-Rearranged Non-Small-Cell Lung Cancer: An Open-Label, Single-Centre, Phase 2, Single-Arm Trial
Drilon A et al. Lancet Oncol 2016;17(12):

24. Cabozantinib in Patients with RET-Rearranged NSCLC
Best confirmed response
Partial response
Stable disease
Maximum reduction from baseline measurement (%)
Best response
% (n) PR
28% (7/25)
ORR 28%
Median PFS: 5.5 months
Median DoR: 7.0 months
Median OS: 9.9 months
Of the 7 patients with confirmed PR, disease shrinkage of ≥30% was noted at the first response assessment in 5 (71%).
Drilon A et al. Lancet Oncol 2016;17(12):