2. Letter from Prof Rolf Stahel
Dear Colleagues It is my pleasure to present this ETOP slide set which has been designed to highlight and summarise key findings in thoracic cancers from the major congresses in This slide set specifically focuses on the IASLC 19th World Conference on Lung Cancer and is available in 4 languages – English, French, Chinese and Japanese. The area of clinical research in oncology is a challenging and ever changing environment. Within this environment, we all value access to scientific data and research which helps to educate and inspire further advancements in our roles as scientists, clinicians and educators. I hope you find this review of the latest developments in thoracic cancers of benefit to you in your practice. If you would like to share your thoughts with us we would welcome your comments. Please send any correspondence to I would like to thank our ETOP members Solange Peters and Martin Reck for their roles as Editors – for prioritising abstracts and reviewing slide content. The slide set you see before you would not be possible without their commitment and hard work. Finally, we are also very grateful to Lilly Oncology for their financial, administrative and logistical support in the realisation of this activity. Yours sincerely, Rolf Stahel President, ETOP Foundation Council

3. ETOP Medical Oncology Slide Deck Editors 2018
Focus: advanced NSCLC (not radically treatable stage III & stage IV)
Dr Solange Peters
Multidisciplinary Oncology Center, Lausanne Cancer Center, Lausanne, Switzerland
Focus: other malignancies, SCLC, mesothelioma, rare tumours
Dr Martin Reck
Department of Thoracic Oncology, Hospital Grosshansdorf, Grosshansdorf, Germany

4. Contents Screening and biomarkers
Early stage and locally advanced NSCLC – Stages I, II and III
Advanced NSCLC – Not radically treatable stage III and stage IV
First line
Later lines
Other malignancies
SCLC, mesothelioma and thymic epithelial tumours

5. Screening and biomarkers

6. PL02.05: Effects of Volume CT Lung Cancer Screening: Mortality Results of the NELSON Randomised-Controlled Population Based Trial – De Koning HJ, et al
Study objective
To assess the use of a screening program in reducing lung cancer mortality
Methods
The NELSON trial is a population-based registry RCT, using registries from the Netherlands and Belgium
General health questionnaires were sent to 606,409 men and women aged 50–74 years identified from the registries
Inclusion criteria included a smoking history >10 cigarettes/day for >30 years or >15 cigarettes/day for >25 years with smoking cessation ≤10 years
30,959 individuals were considered eligible and 15,792 were randomised 1:1 to CT screening vs. no screening
CT screening was undertaken at Years 1, 2, 4, 6.5 and 10
The CT images were read centrally, and volume and volume doubling time of nodules was used to make decisions on the screening results
There was an expert causes of death committee and follow-up was made using national registries
De Koning HJ et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.05

7. PL02.05: Effects of Volume CT Lung Cancer Screening: Mortality Results of the NELSON Randomised-Controlled Population Based Trial – De Koning HJ, et al
Key results
Screening uptake, n (%)
Indeterminate test result, n (%)
Positive test result, n (%)
Lung cancer detection, n (%)
Positive predictive value of positive test result, %
Round 1
7,557 (95.6)
1,451 (19.2)
197 (2.6)
70 (0.9) 36
Round 2
7,295 (92.3)
480 (6.6)
131 (1.8)
55 (0.8) 42
Round 3
6,922 (87.6)
471 (6.8)
165 (2.4)
75 (1.1) 45
Round 4
5,279 (66.8)
101 (1.9)
105 (2.0)
43 (0.8) 41
Total
27,053 (85.6)
2,503 (9.3)
598 (2.2)
243 (0.9)
De Koning HJ et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.05

8. Cumulative absolute number of first lung cancers
PL02.05: Effects of Volume CT Lung Cancer Screening: Mortality Results of the NELSON Randomised-Controlled Population Based Trial – De Koning HJ, et al
Key results (cont.)
Cumulative absolute number of first lung cancers
Stage at diagnosis
Netherlands cancer registry
Control arm
Screen arm
60%
50%
40%
30%
20%
10% 0%
Stage
Cumulative absolute number of first lung cancers
Time since randomisation
100
150
200
250
300
350
400
450 50 1 2 3 4 5 6 10 7 8 9
Control
Screen
De Koning HJ et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.05

9. Cumulative lung cancer deaths (men only)
PL02.05: Effects of Volume CT Lung Cancer Screening: Mortality Results of the NELSON Randomised-Controlled Population Based Trial – De Koning HJ, et al
Key results (cont.)
Cumulative lung cancer deaths (men only)
Cumulative lung cancer deaths
Years since randomisation 50
100
150
200
250 1 2 3 4 5 6 10 7 8 9
Control arm: 214 lung cancer deaths
Screen arm:
157 lung cancer deaths
De Koning HJ et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.05

10. PL02.05: Effects of Volume CT Lung Cancer Screening: Mortality Results of the NELSON Randomised-Controlled Population Based Trial – De Koning HJ, et al
Key results (cont.)
Conclusions
With the use of CT screening, men at high-risk for lung cancer in the screening group had a 26% reduced risk of dying from lung cancer compared with the control arm
The reductions in mortality in women in the screening group were consistently more favourable than the men
Lung cancer mortality rate ratio (95%CI)
Year 8
Year 9
Year 10
Males
0.75 (0.59, 0.95); p=0.015
0.76 (0.60, 0.95); p=0.012
0.74 (0.60, 0.91); p=0.003
Females
0.39 (0.18, 0.78); p=0.0037)
0.47 (0.25, 0.84); p=0.0069
0.61 (0.35, 1.04); p=0.0543
De Koning HJ et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.05

11. MA03.05: New Subsolid Pulmonary Nodules in Lung Cancer Screening: The NELSON Trial – Heuvelmans MA, et al
Study objective
To assess the occurrence and lung cancer frequency of new subsolid nodules as part of a screening programme and to determine whether a more aggressive follow-up approach is necessary
Methods
This analysis of patients from the NELSON lung cancer screening study included subsolid nodules identified at the 1, 3 and 5.5 years screening rounds
A nodule was classified as (pre-)malignancy when it was diagnosed as lung cancer through diagnostic workup which included a histological assessment
Key results
60 new subsolid nodules that were not visible in retrospect were identified in 51 (0.7%; 51/7295) participants
43 (72%) were part-solid and 17 (28%) were non-solid
6% (3/51) of participants with a new subsolid nodule were (pre-)malignancy
With follow-up screening 65% (33/49) of subsolid nodules were resolving
Conclusion
A more aggressive follow-up approach is not required for new subsolid nodules than for baseline subsolid nodules
Heuvelmans MA et al. J Thorac Oncol 2018;13(suppl):Abstr MA03.05

12. OA03.03: Phase 2B of Blueprint PD-L1 Immunohistochemistry Assay Comparability Study – Kerr KM, et al
Study objective
To examine the comparability of PD-L1 scoring across various assays using three types of samples from the same tumour: large section, core needle/forceps biopsy and fine needle aspiration cytology samples
Methods
Thirty-one samples were taken prospectively in the routine clinical practice of 11 pathologists: 17 adenocarcinoma, 12 squamous cell carcinoma and 2 large cell
The 22C3 (Dako), 28-8 (Dako), SP142 (Ventana), SP263 (Ventana), (Dako) assays were conducted by HistoGeneX
Anonymised sample slides were scanned, and then uploaded and scored via the Pathomation Digital Pathology System
Twenty-four pathologists scored the images, readers were not aware of which assay they were reading
There was no immune cell scoring
Kerr KM et al. J Thorac Oncol 2018;13(suppl):Abstr OA03.03

13. OA03.03: Phase 2B of Blueprint PD-L1 Immunohistochemistry Assay Comparability Study – Kerr KM, et al
Key results
Between the readers agreement was generally ‘moderate’ to ‘near perfect’ with data for the TPS scores similar to those in previous studies
There was good agreement between assays around specified cut points
Mean and median values varied between assays, but not between sample types
Conclusions
In PD-L1 IHC testing, Blueprint 2B reaffirms the data around assay performance and inter- observer variability
Good comparability between TPS was seen between matched samples (large section, core needle/forceps biopsy and fine needle aspiration cytology) from the same tumour
Assay
Aspirate
(Mean, median)
Biopsy
Resection
Aspirate vs. biopsy
(p-value)
Aspirate vs. resection
Biopsy vs. resection
22C3
19.0, 0.9
18.2, 0.7
22.2, 0.5
0.31
0.90
0.26
28-8
21.6, 1.7
21.6, 2.6
0.13
0.79
0.19
73-10
26.0, 2.4
26.3, 2.8
27.4, 3.3
0.86
0.18
0.41
SP142
5.2, 0
4.2, 0.04
6.8, 0.09
0.57
0.49
0.12
SP263
22.4, 1.5
23.7, 2.7
25.3, 4.2
0.031
0.25
Kerr KM et al. J Thorac Oncol 2018;13(suppl):Abstr OA03.03

14. Early and locally advanced NSCLC Stages I, II and III

15. OA01.06: DETERRED: Phase II Trial Combining Atezolizumab Concurrently with Chemoradiation Therapy in Locally Advanced Non-Small Cell Lung Cancer – Lin LH, et al
Study objective
To examine the efficacy and safety of atezolizumab combined with carboplatin, paclitaxel and radiation in patients with locally advanced NSCLC
Part 1
Concurrent chemoradiation*
(n=10)
Consolidation chemo** + atezolizumab 1200 mg IV q3w x 2 cycles
Maintenance atezolizumab up to 1 year
Key patient inclusion criteria
Locally advanced NSCLC
(n=40)
Part 2
Concurrent chemoradiation* + atezolizumab mg q3w IV
(n=30)
Consolidation chemo** + atezolizumab mg IV q3w x 2 cycles
Maintenance atezolizumab up to 1 year
Primary endpoint
Safety
Secondary endpoints
1-year PFS, grade 3+ radiation pneumonitis, biomarker correlates of outcomes
*Carboplatin AUC2 + paclitaxel 50 mg/m2 + radiation (60–66 Gy) q1w; **carboplatin AUC6 + paclitaxel 200 mg/m2 q3w
Lin LH et al. J Thorac Oncol 2018;13(suppl):Abstr OA01.06

16. OA01.06: DETERRED: Phase II Trial Combining Atezolizumab Concurrently with Chemoradiation Therapy in Locally Advanced Non-Small Cell Lung Cancer – Lin LH, et al
Key results
Grade 3+ pulmonary complications:
Part 1: 1 grade 3 dyspnoea, 2 grade 2 radiation pneumonitis
Part 2: 2 grade 2 radiation pneumonitis, 1 grade 3+ radiation pneumonitis, 1 grade 4 respiratory failure NOS
Part 1
(n=10)
Part 2
(n=30)
All AEs, n
697
574
Grade 3+ AEs, n 54 48
Patients with grade 3+, n (%)
6 (60)
17 (57)
AEs leading to withdrawal, n (%)
3 (30)
3 (10)
Patients with atezolizumab grade 3+ AEs, n (%)
7 (23)
Lin LH et al. J Thorac Oncol 2018;13(suppl):Abstr OA01.06

17. Early preliminary efficacy results
OA01.06: DETERRED: Phase II Trial Combining Atezolizumab Concurrently with Chemoradiation Therapy in Locally Advanced Non-Small Cell Lung Cancer – Lin LH, et al
Key results (cont.)
Conclusions
In patients with locally advanced NSCLC, concurrent atezolizumab and chemoradiation therapy is feasible with no excessive toxicities
In the concurrent atezolizumab and chemoradiation arm early analysis suggests promising activity
Early preliminary efficacy results
Median follow-up 1.3 years for part 1, 0.75 years for part 2
Percent survival
100 50 4 8 12 16 20 24 28
Time, months
Part 1
Part 2
PFS
Percent survival
100 50 4 8 12 16 20 24 28
Time, months
Part 1
Part 2 OS
Median PFS, months
1-year PFS
Median OS, months
1-year OS
Part 1
20.1 60
Part 2 NR 66 70
Lin LH et al. J Thorac Oncol 2018;13(suppl):Abstr OA01.06

18. OA02.01: Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small Cell Lung Cancer (NSCLC) – Doebele RC, et al
Study objective
To examine the efficacy and safety of entrectinib, a CNS active, selective ROS1, TRK and ALK inhibitor, in patients with locally advanced or metastatic ROS1 fusion-positive NSCLC
Key patient inclusion criteria
Locally advanced or metastatic NSCLC
ROS1 fusion positive
ROS1 inhibitor naïve
Pooled analysis of 3 phase 1 and 2 studies – STARTRK-2, STARTRK-1 and ALKA
(n=53 ROS1+; N=355 all)
Entrectinib 600 mg/day q4w PD
Primary endpoint
ORR, DoR (BICR by RECIST v1.1)
Secondary endpoints
CBR, PFS, OS, safety
Intracranial responses in patients with CNS disease
Doebele RC et al. J Thorac Oncol 2018;13(suppl):Abstr OA02.01

19. OA02.01: Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small Cell Lung Cancer (NSCLC) – Doebele RC, et al
Key results
The most common grade ≥3 AEs occurring in >1% were weight increased (5.1%), anaemia (4.5%), fatigue (2.8%), diarrhoea (1.4%) and increased AST (1.1%)
Conclusions
Entrectinib provided clinically meaningful responses in patients with ROS1 fusion-positive locally advanced or metastatic NSCLC with and without CNS metastases
Entrectinib had a manageable safety profile with low rates of discontinuation
PFS
12-month event-free probability: 0.65
Response, n (%)
CNS disease at baseline (n=23)
No CNS disease at baseline (n=30)
ORR, n (%) [95%CI]
17 (73.9) [51.6, 89.8]
24 (80.0) [61.4, 92.3] CR
3 (10.0) PR
17 (73.9)
21 (70.0) SD
1 (3.3) PD
4 (17.4)
Non-CR/PD
Missing/unevaluable
2 (8.7)
2 (6.7)
CBR, n (%) [95%CI]
41 (77.4) [63.8, 87.7]
100
Total
Censored
Median (95%CI)
Total [N=53]: 19 [12.2, 36.6] 80 60
PFS by BICR, % 40 20 53 6 37 12 28 18 8 24 6 30 3 36 1 42
Time, months
No. at risk 43 32 15 6 5 1
Doebele RC et al. J Thorac Oncol 2018;13(suppl):Abstr OA02.01

20. Atezolizumab 1200 mg q3w for 12 months
MA04.09: Neoadjuvant Atezolizumab in Resectable Non-Small Cell Lung Cancer (NSCLC): Updated Results from a Multicenter Study (LCMC3) – Rusch VW, et al
Study objective
To examine major pathologic response rate (MPR) and biomarkers in patients with resectable stage 1B–IIIB NSCLC receiving neoadjuvant atezolizumab (interim analysis of 54 patients from Part 1 of the study)
Part 1 (primary)
Part 2 (exploratory)
Clinical benefit
Key patient inclusion criteria
Stage IB–IIIB resectable NSCLC
(n=54 of 180 planned)
Atezolizumab mg D1, 22
2 cycles
Atezolizumab mg q3w for 12 months
Surgical resection
SoC adjuvant therapy
Primary endpoint
MPR
Secondary endpoints
Safety, response by PD-L1, OS, DFS
Rusch VW et al. J Thorac Oncol 2018;13(suppl):Abstr MA04.09

21. Efficacy population (n=45)
MA04.09: Neoadjuvant Atezolizumab in Resectable Non-Small Cell Lung Cancer (NSCLC): Updated Results from a Multicenter Study (LCMC3) – Rusch VW, et al
Key results
Pathologic Regression, %
MPR is defined as ≤10% viable tumour cells
PD-L1 expression:
TC1/2/3 or IC1/2/3
TC0 and IC0
Unknown
RECIST response:
Tobacco use:
Histology: PR SD
Never
Current
Previous
Non-squamous
Squamous
RECIST response
Tobacco use
Histology
Pathologic regression (%)
Outcome
Efficacy population (n=45)
MPR, n (%) [95%CI]
10 (22) [11, 37]
pCR, n (%)
3 (7)
ORR, n (%) PR SD
42 (93) PD
Rusch VW et al. J Thorac Oncol 2018;13(suppl):Abstr MA04.09

22. Safety population (n=54)
MA04.09: Neoadjuvant Atezolizumab in Resectable Non-Small Cell Lung Cancer (NSCLC): Updated Results from a Multicenter Study (LCMC3) – Rusch VW, et al
Key results (cont.)
Conclusion
In patients with resectable, early stage NSCLC, neoadjuvant atezolizumab was well tolerated and demonstrated promising clinical activity with no major delays to surgery or interference with surgical resection
Incidence, n (%)
Safety population (n=54)
≥1 AE
Grade 3–4
Grade 5
51 (94)
15 (28)
1* (2)
Treatment related AE
32 (59)
3 (6)
Serious AE
16 (30)
AE leading to withdrawal
2 (4)
*Sudden death not related to study treatment, approximately 2 weeks after surgery
Rusch VW et al. J Thorac Oncol 2018;13(suppl):Abstr MA04.09

23. Advanced NSCLC Not radically treatable stage III and stage IV
First line

24. PL02.03: Brigatinib vs Crizotinib in Patients With ALK Inhibitor-Naive Advanced ALK+ NSCLC: First Report of a Phase 3 Trial (ALTA-1L) – Camidge R, et al
Study objective
To assess the efficacy and safety of brigatinib vs. crizotinib in ALK inhibitor-naïve advanced ALK+ NSCLC
Brigatinib 180 mg/day
(7-day lead-in at 90 mg)
(n=137)
PD/ toxicity/ other
Key patient inclusion criteria
Stage IIIB/IV ALK+ NSCLC
No prior ALK inhibitor
≤1 prior systemic therapy
(n=275)
Stratification
Brain metastases (yes vs. no)
Prior chemotherapy (yes vs. no) R
1:1
Crizotinib 250 mg bid*
(n=138)
PD/ toxicity/ other
Primary endpoint
BIRC-assessed PFS (RECIST v1.1)
Secondary endpoints
ORR, intracranial ORR, intracranial PFS, OS, safety
Camidge R et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.03
*Crossover to brigatinib permitted at PD

25. Patients with events, n (%)
PL02.03: Brigatinib vs Crizotinib in Patients With ALK Inhibitor-Naive Advanced ALK+ NSCLC: First Report of a Phase 3 Trial (ALTA-1L) – Camidge R, et al
Key results
1-year OS probability: brigatinib 85% (95%CI 76, 91); crizotinib 86% (95%CI 77, 91)
BIRC-assessed PFS
Treatment
Patients with events, n (%)
Median PFS, mths (95%CI)
1-year PFS, %
(95%CI)
Brigatinib
36 (26)
NR (NR, NR)
67 (56, 75)
Crizotinib
63 (46)
9.8 (9.0, 12.9)
43 (32, 53)
100
HR for disease progression or death (95%CI 0.33, 0.74); p= by log-rank test 80 60
PFS, % of patients 40
Brigatinib (n=137)
Crizotinib (n=138) 20 3 6 9 12 15 18
Time, months
From NEJM, Camidge R, et al., Brigatinib versus Crizotinib in ALK-positive non–small-cell lung cancer, DOI: /NEJMoa Copyright © (2018) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
Camidge R et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.03

26. PL02.03: Brigatinib vs Crizotinib in Patients With ALK Inhibitor-Naive Advanced ALK+ NSCLC: First Report of a Phase 3 Trial (ALTA-1L) – Camidge R, et al
Key results (cont.)
Intracranial PFS in Patients With Any Brain Metastases at Baseline
Treatment
Median intracranial PFS, mths (95%CI)
1-Year PFS, % (95%CI)
Brigatinib
NR (11.0, NR)
67 (47, 80)
Crizotinib
5.6 (4.1, 9.2)
21 (6, 42)
100
HR 0.27 (95%CI 0.13, 0.54); p< by log-rank test 80 60
Intracranial PFS, % of patients 40
Brigatinib (n=43)
Crizotinib (n=47) 20 3 6 9 12 15 18
Time, months
From NEJM, Camidge R, et al., Brigatinib versus Crizotinib in ALK-positive non–small-cell lung cancer, DOI: /NEJMoa Copyright © (2018) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
Camidge R et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.03

27. PL02.03: Brigatinib vs Crizotinib in Patients With ALK Inhibitor-Naive Advanced ALK+ NSCLC: First Report of a Phase 3 Trial (ALTA-1L) – Camidge R, et al
Key results (cont.)
Interstitial lung disease/pneumonitis at any time occurred in 4% (5/136) with brigatinib and 2% (3/137) with crizotinib
Early-onset interstitial lung disease/pneumonitis (within 14 days of treatment initiation) occurred in 3% with brigatinib (onset: D3–8) and none reported with crizotinib
Dose reduction due to AEs (brigatinib/crizotinib): 29%/21%
Discontinuation due to AEs (brigatinib/crizotinib): 12%/9%
Conclusions
In patients with ALK inhibitor-naïve advanced ALK+ NSCLC, brigatinib provided superior PFS by BIRC when compared with crizotinib at the first planned interim analysis
This was seen across all subgroups, with the short follow-up emphasising CNS progression among those with baseline CNS disease
Brigatinib was well tolerated and early-onset pneumonitis (within 14 days of treatment initiation), a side effect that may be unique to brigatinib, was rare
Camidge R et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.03

28. OA05.07: IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC – Papadimitrakopoulou VA, et al
Study objective
To evaluate 1L pemetrexed + carboplatin or cisplatin with or without atezolizumab in patients with stage IV non-squamous NSCLC without EGFR or ALK driver mutations
Atezolizumab* + carboplatin/ cisplatin + pemetrexed** (4 or 6 cycles)
(n=292)
Atezolizumab + pemetrexed maintenance
PD/ loss of benefit
Key patient inclusion criteria
Stage IV non-squamous NSCLC
Chemotherapy naïve
Without EGFR or ALK genetic alterations
(n=578)
Stratification
Sex
Smoking status
ECOG PS
Chemotherapy regimen R
1:1
Carboplatin/cisplatin + pemetrexed** (4 or 6 cycles)
(n=286)
Pemetrexed maintenance
PD/ loss of benefit
Co-primary endpoints
Investigator-assessed PFS, OS
Secondary endpoints
Investigator-assessed ORR and DoR, PRO and safety
*Atezolizumab 1200 mg IV q3w; **carboplatin AUC6 mg/mL/min IV q3w or cisplatin 75 mg/m2 IV q3w + pemetrexed 500 mg/m2 IV q3w
Papadimitrakopoulou VA et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.07

29. Investigator-assessed PFS
OA05.07: IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC – Papadimitrakopoulou VA, et al
Key results
Investigator-assessed PFS
HR 0.60 (95%CI 0.49, 0.72); p<0.0001
Minimum follow-up, 11.7 months
Median follow-up, 14.8 months
100 80
Atezolizumab + carboplatin/cisplatin + pemetrexed
Carboplatin/cisplatin + pemetrexed 60
Progression-free survival, % 40 20
5.2 months
(95%CI 4.3, 5.6)
7.6 months
(95%CI 6.6, 8.5)
292
286 1
280
273 2
260
236 3
231
195 4
224
178 5
191
142 6
169
115 7
149 98 8
140 87 9
120 72 10
110 59 11
109 53 12 88 44 13 74 39 14 48 15 43 11 16 31 6 17 26 18 11 3 19 10 20 2 21 22 23
Time, months
No. at risk
Atezolizumab + C + P
C + P
Papadimitrakopoulou VA et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.07

30. OA05.07: IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC – Papadimitrakopoulou VA, et al
Key results (cont.)
Interim OS Analysis
HR 0.81 (95%CI 0.64, 1.03); p=0.0797
Minimum follow-up: 11.7 months
Median follow-up: 14.8 months
100
Atezolizumab + carboplatin/cisplatin + pemetrexed
Carboplatin/cisplatin + pemetrexed) 80 60
Overall survival, % 40 20
13.6 months
(95%CI 11.4, 15.5)
18.1 months
(95%CI 13.0, NE)
292
286 1
284
278 2
273
265 3
258
246 4
252
233 5
239
219 6
228
210 7
212
193 8
202
179 9
194
166 10
187
163 11
179
151 12
168
147 13
140
126 14
107 92 15 79 58 16 62 43 17 48 30 18 32 22 19 23 15 20 10 8 21 7 4 22 1 2 23
Time, months
No. at risk
Atezolizumab + C + P
C + P
Data cutoff: May 22, 2018
Papadimitrakopoulou VA et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.07

31. OA05.07: IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC – Papadimitrakopoulou VA, et al
Key results (cont.)
Conclusions
In patients with stage IV non-squamous NSCLC, atezolizumab added to 1L carboplatin/cisplatin + pemetrexed improved mPFS in the ITT population and across key clinical subgroups; no significant improvement in OS was seen in the interim data
The combination of atezolizumab + carboplatin or cisplatin + pemetrexed had a safety profile consistent with that for the individual therapies
Atezolizumab + carboplatin/ cisplatin + pemetrexed
(n=291)
Carboplatin/cisplatin + pemetrexed
(n=274)
All-cause AEs, n (%)
Grade 3–4
Grade 5
286 (98)
181 (62)
21 (7)
266 (97)
147 (54)
14 (5)
TRAEs, n (%)
267 (92)
239 (87)
SAEs, n (%)
134 (46)
84 (31)
AEs leading to withdrawal, n (%)
Any treatment
Atezolizumab
69 (24)
44 (15)
48 (18)
AESI, n (%)
141 (49)
104 (38)
Papadimitrakopoulou VA et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.07

32. OA07.01: Phase II Study of Pembrolizumab for Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Following Completion of Locally Ablative Therapy (LAT) – Bauml JM, et al
Study objective
To examine the efficacy and safety of pembrolizumab following locally ablative therapy in patients with oligometastatic NSCLC
Pembrolizumab 200 mg q3w for 6 months
Key patient inclusion criteria
NSCLC
Up to 4 metastases (any site)
No limit on prior therapies
No PD-(L)1 therapies
PS 0–1
(n=45)
Locally ablative therapy to all known sites of disease
SD or better
Pembrolizumab 200 mg q3w for 6 months
PD or patient preference
Off study
Primary endpoints
PFS, safety
Secondary endpoints
OS, QoL
Bauml JM et al. J Thorac Oncol 2018;13(suppl):Abstr OA07.01

33. Progression-free survival
OA07.01: Phase II Study of Pembrolizumab for Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Following Completion of Locally Ablative Therapy (LAT) – Bauml JM, et al
Key results
Grade 3 or 4 TRAEs observed in either 1 or 2 patients for each included pain, dyspnoea, nausea, pneumonitis, colitis and adrenal insufficiency
Conclusion
In patients with oligometastatic NSCLC, pembrolizumab after local ablative therapy was feasible, well tolerated and shows interesting survival outcomes in this small selected patient subgroup
Progression-free survival
Probability
Months from start of definitive therapy
1.0
0.8
0.6
0.4
0.2
0.0 45 6 36 12 28 18 24 10 30 5 4 42 48
Median PFS: 19.1 months (95%CI 11.5, 26.7)
Overall survival
Probability
Months from start of definitive therapy
1.0
0.8
0.6
0.4
0.2
0.0 45 6 44 12 39 18 27 24 30 11 36 42 48
Median OS: NR (95%CI not defined)
No. at risk
No. at risk
Bauml JM et al. J Thorac Oncol 2018;13(suppl):Abstr OA07.01

34. Advanced NSCLC Not radically treatable stage III and stage IV
Later lines

35. Key patient inclusion criteria Unresectable, stage III NSCLC
PL02.01: Overall Survival with Durvalumab Versus Placebo After Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC – Antonia SJ, et al
Study objective
To examine the co-primary endpoint of OS from the PACIFIC study of durvalumab vs. placebo in patients with stage III, unresectable NSCLC without progression after concurrent chemoradiotherapy
Key patient inclusion criteria
Unresectable, stage III NSCLC
No progression after platinum-based concurrent chemoradiotherapy
WHO PS 0–1
(n=713)
Durvalumab 10 mg/kg q2w for up to 12 months
(n=476)
Stratification
Sex
Age
Smoking history R
2:1
Placebo for up to 12 months
(n=237)
Co-primary endpoints
PFS (RECIST v1.1; by BICR), OS
Secondary endpoints
ORR, DoR, TTDM, PFS2 by investigator, safety, PROs
Antonia SJ et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.01

36. No. of events / No. of patients (%)
PL02.01: Overall Survival with Durvalumab Versus Placebo After Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC – Antonia SJ, et al
Key results
OS (ITT)
No. of events / No. of patients (%)
Median OS, months (95%CI)
Durvalumab
183/476 (38.4)
NR (34.7, NR)
Placebo
116/237 (48.9)
28.7 (22.9, NR)
Probability of OS
1.0
0.8
0.6
0.4
0.2
0.0
476
237 3
464
220 6
431
198 9
415
178 12
385
170 15
364
155 18
343
141 21
319
130 24
274
117 27
210 78 30
115 42 33 57 36 23 39 2 1 45
No. at risk
Durvalumab
Placebo
83.1%
66.3%
55.6%
75.3%
Time from randomisation, months
HR 0.68 (99.73%CI 0.469, 0.997); p=
From NEJM, Antonia SJ, et al., Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC, DOI: /NEJMoa Copyright © (2018) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
Antonia SJ et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.01

37. PL02.01: Overall Survival with Durvalumab Versus Placebo After Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC – Antonia SJ, et al
Key results (cont.)
Updated PFS by BICR (ITT)
No. of events / No. of patients (%)
Median PFS, months (95%CI)
Durvalumab
243/476 (51.1)
17.2 (13.1, 23.9)
Placebo
173/237 (73.0)
5.6 (4.6, 7.7)
1.0
HR 0.51 (95%CI 0.41, 0.63)
0.8
55.7%
0.6
49.5%
Probability of PFS
0.4
34.4%
0.2
26.7%
0.0
476
237 3
377
163 6
302
106 9
268 86 12
213 67 15
188 55 18
163 46 21
143 39 24
116 32 27 83 24 30 43 10 33 23 5 36 1 39
Time from randomisation, months
No. at risk
Durvalumab
Placebo
From NEJM, Antonia SJ, et al., Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC, DOI: /NEJMoa Copyright © (2018) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
Antonia SJ et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.01

38. Incidence of new lesions by BICR (ITT)
PL02.01: Overall Survival with Durvalumab Versus Placebo After Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC – Antonia SJ, et al
Key results (cont.)
Incidence of new lesions
by BICR (ITT)
Updated time to death or distant metastasis (TTDM) by BICR (ITT)
Median TTDM, months (95%CI)
Durvalumab
28.3 (24.0, 34.9)
Placebo
16.2 (12.5, 21.1)
Site, n (%)
Durvalumab (n=476)
Placebo (n=237)
Any new lesion
107 (22.5)
80 (33.8)
Lung
60 (12.6)
44 (18.6)
Lymph nodes
31 (6.5)
27 (11.4)
Brain
30 (6.3)
28 (11.8)
Liver
9 (1.9)
8 (3.4)
Bone
8 (1.7)
7 (3.0)
Adrenal
3 (0.6)
5 (2.1)
Other
10 (2.1)
Probability of death or distant metastasis
1.0
0.8
0.6
0.4
0.2
0.0
476
237 3
419
189 6
357
139 9
316
118 12
259 95 15
223 77 18
194 64 21
163 54 24
129 39 27 92 30 46 33 25 5 36 1
Time from randomisation, months
TTDM HR 0.53
(95%CI 0.41, 0.68)
No. at risk
Durvalumab
Placebo
From NEJM, Antonia SJ, et al., Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC, DOI: /NEJMoa Copyright © (2018) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
Antonia SJ et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.01

39. PL02.01: Overall Survival with Durvalumab Versus Placebo After Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC – Antonia SJ, et al
Key results (cont.)
Conclusions
In patients with stage III NSCLC, compared with placebo, durvalumab provided significant and clinically meaningful improvement in OS
After a longer follow-up of treatment with durvalumab, there were no new safety signals
Durvalumab
(n=475)
Placebo (n=234)
Any-grade all-causality AEs, n (%)
460 (96.8)
222 (94.9)
Grade 3/4
145 (30.5)
61 (26.1)
Outcome of death
21 (4.4)
15 (6.4)
Leading to discontinuation
73 (15.4)
23 (9.8)
Serious AEs, n (%)
138 (29.1)
54 (23.1)
Any-grade pneumonitis/radiation pneumonitis, n (%)
161 (33.9)
58 (24.8)
17 (3.6)
7 (3.0)
5 (1.1)
5 (2.1)
30 (6.3)
10 (4.3)
Antonia SJ et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.01

40. Poziotinib 16 mg/day PO (dose reductions to 12 or 8 mg permitted)
OA02.06: A Phase II Trial of Poziotinib in EGFR and HER2 exon 20 Mutant Non-Small Cell Lung Cancer (NSCLC) – Heymach JV, et al
Study objective
To examine the efficacy and safety of poziotinib in patients with metastatic NSCLC and harbouring mutations or insertions in EGFR (except T790M) and HER2 exon 20
Key patient inclusion criteria
Metastatic NSCLC
Cohort 1: EGFR exon 20 mutant (except acquired T790M)
Cohort 2: HER2 exon 20 mutations/insertions
Unlimited prior systemic or targeted therapies
(n=50)
Poziotinib 16 mg/day PO (dose reductions to 12 or 8 mg permitted)
PD/death/ toxicity
Primary endpoint
ORR (RECIST v1.1)
Secondary endpoints
PFS, OS, DCR, DoR, safety
Heymach JV et al. J Thorac Oncol 2018;13(suppl):Abstr OA02.06

41. OA02.06: A Phase II Trial of Poziotinib in EGFR and HER2 exon 20 Mutant Non-Small Cell Lung Cancer (NSCLC) – Heymach JV, et al
Key results
The ORR was 55% and 50% in patients with EGFR and HER2 exon 20 mutant NSCLC, respectively
The most common grade 3–4 AEs occurring in ≥5% were skin rash (34.9%), diarrhoea (17.5%), paronychia (9.5%) and nausea (7.9%)
Conclusion
In heavily pre-treated patients with metastatic EGFR or HER2 exon 20 mutant NSCLC, poziotinib demonstrated anti-tumour activity and the EGFR-related AEs were manageable
PFS in ITT population
PFS in HER2 cohort (n=13)
100
100
Median PFS 5.5 months
(95%CI 5.2, NA)
Median PFS 5.1 months 75
Percent survival 50
Percent survival 50 25 5 10 15 2 4 6 8 10
Months
Months
Heymach JV et al. J Thorac Oncol 2018;13(suppl):Abstr OA02.06

42. MA04.02: Responses and Durability in NSCLC Treated With Pegilodecakin and Anti-PD-1 – Garon EB, et al
Study objective
To examine the efficacy and safety of pegilodecakin, an agent that stimulates the survival and expansion of intratumoral, antigen-activated CD8+ T cells, combined with pembrolizumab or nivolumab in previously treated patients with NSCLC
Pegilodecakin 10–20 mg/day SC + pembrolizumab 2 mg/kg IV q3w or nivolumab 3 mg/kg IV q2w
Key patient inclusion criteria
NSCLC
Pre-treated
(n=34)
Primary endpoint
ORR (RECIST v1.1)
Secondary endpoints
PFS, OS, DCR, safety
Garon EB et al. J Thorac Oncol 2018;13(suppl):Abstr MA04.02

43. MA04.02: Responses and Durability in NSCLC Treated With Pegilodecakin and Anti-PD-1 – Garon EB, et al
Key results
Grade 3–4 AEs occurring in 5% of patients included anaemia (17%), thrombocytopenia (17%), fatigue (17%), hypertriglyceridaemia (10%), pyrexia (6.9%) and maculopapular rash (6.9%)
Conclusion
In pre-treated patients with NSCLC, pegilodecakin + anti-PD-1 therapy was well tolerated providing clinically meaningful responses and long duration of survival
Clinical benefit was observed in those with low PD-L1, low TMB and liver metastases
Population (n=evaluable/enrolled)
mPFS, months
mOS, months
ORR, %
DCR, %
Pegilodecakin (n=7/9)
1.8
15.4 - 57
Pegilodecakin + nivolumab (n=22/29) NR 41 82
Pegilodecakin + pembrolizumab (n=5/5) 11
32.2 40
100
Pegilodecakin + anti-PD-1 (n=27/34 pooled) 85
PD-L1 negative (<1%; n=12)
5.7 33 92
PD-L1 low (1–49%; n=3)
8.9 67
PD-L1 high (≥50%; n=5)
10.7 80
TMB low (≤243 mut/exome; n=8)
10.3 63
TMB high (>243 mut/exome; n=2)
7.2
14.1 50
Liver metastases (n=8)
9.8
12.3 75
Garon EB et al. J Thorac Oncol 2018;13(suppl):Abstr MA04.02

44. OA05.01: Efficacy/Safety of Entinostat (ENT) and Pembrolizumab (PEMBRO) in NSCLC Patients Previously Treated with Anti-PD-(L)1 Therapy – Hellmann MD, et al
Study objective
To examine the efficacy and safety of entinostat, a selective histone deacetylase (HDAC) inhibitor, combined with pembrolizumab in patients with recurrent or metastatic NSCLC previously treated with an anti-PD-(L)1 therapy
Key patient inclusion criteria
Recurrent or metastatic NSCLC
Prior chemotherapy in the advanced/metastatic setting
Prior progression on anti-PD-(L)1 therapy
Unselected by PD-L1 expression
ECOG PS <2
(n=76)
Entinostat 5 mg PO q1w +
pembrolizumab 200 mg IV q3w
PD/ death/ toxicity
Primary endpoint
ORR (irRECIST)
Secondary endpoints
PFS, OS, safety
Hellmann MD et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.01

45. OA05.01: Efficacy/Safety of Entinostat (ENT) and Pembrolizumab (PEMBRO) in NSCLC Patients Previously Treated with Anti-PD-(L)1 Therapy – Hellmann MD, et al
Key results
ORR with entinostat + pembrolizumab was 10% (7/72 patient, 95%CI 4, 19)
Median DoR was 5.3 months
7 (9.2%) patients experienced grade 3/4 related irAEs: 3 pneumonitis, 3 colitis and 1 hyperthyroidism
Conclusion
In patients with NSCLC who have progressed on prior PD-(L)1 blockade, entinostat + pembrolizumab was well tolerated and demonstrated anti-tumour activity that was independent of pre-treatment PD-L1 expression and response to prior PD-1 blockade 65 50 35 20 5
Change from baseline, %
–10
–25
–40
–55
–70
PD SD PR Confirmed
–85
–100
Hellmann MD et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.01

46. OA05.03: Safety and Clinical Activity of Adoptive Cell Transfer Using Tumor Infiltrating Lymphocytes (TIL) Combined with Nivolumab in NSCLC – Creelan BC, et al
Study objective
To examine the activity and safety of tumour infiltrating lymphocyte (TIL) adoptive cell transfer combined with nivolumab in patients with stage IV NSCLC
Key patient inclusion criteria
Stage IV NSCLC
Safely resectable confirmed metastases
RECIST measurable disease
≥5 prior therapies
No corticosteroids
(n=13)
PR/ clinical benefit
Nivolumab q4w for 1 year
Resection of lesion for TIL manufacture; nivolumab 240 mg q2w, 4 doses
Cyclophosphamide 60 mg/kg + Mesna D–7, –6 then fludarabine 25 mg/m2 D–5 to –1;
D0 TIL infusion (≥20·109–1010 CD3+ cells); IL-2 IV* until D6;
nivolumab 480 mg q4w from D29 up to 1 year
PD/SD
Primary endpoint
Safety/tolerability
Secondary endpoints
Efficacy, PK, PD, tumour proteomics, whole exome sequencing, transcriptomics
*IL-2 intermediate dose:18 miU/m2 over 6, 12 and 24 hours then 4.5 miU/m2 over 24 hours x 3) on D1–6
Creelan BC et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.03

47. AEs associated with cyclophosphamide, fludarabine, TIL and/or IL-2
OA05.03: Safety and Clinical Activity of Adoptive Cell Transfer Using Tumor Infiltrating Lymphocytes (TIL) Combined with Nivolumab in NSCLC – Creelan BC, et al
Key results
AEs attributed to any treatment post-TIL
100
AEs associated with cyclophosphamide, fludarabine, TIL and/or IL-2
(n=10) 80 60
Worst grade event, % 40 20
Fever
Chills
Pain
Anaemia
Nausea
Hypoxia
Diarrhoea
Anorexia
Dysphagia
Dyspnoea
Dizziness
Gastritis
Stroke
Vomiting
Pruritus
Confusion
Dry eye
Dry skin
Tremor
Hypotension
Dehydration
Dry mouth
Dysgeusia
Headache
Urticaria
Wheezing
Hyponatremia
Hypocalcemia
Hyperkalemia
INR increased
Oedema limbs
Hypothyroidism
Hypokalemia
Hyperglycaemia
Lung infection
Hypertension
Weight loss
Conjunctivitis
Constipation
Depression
Menorrhagia
Rash acneiform
Abdominal pain
Genital oedema
Hypernatremia
Mucositis oral
Hypoalbuminemia
Sinus tachycardia
Hypomagnesemia
Urinary urgency
Hypernatremia
Hypophosphatemia
Hypermagnesemia
Pulmonary oedema
Creatinine increased
Acute kidney injury
Urinary incontinence
Platelet count decreased
Non-cardiac chest pain
Urinary tract infection
Infections and infestations
Blood bilirubin increased
Lymphocyte count decreased
White blood cell decreased
Neutrophil count decreased
Alkaline phosphatase increased
Aspartate aminotransferase increased
Alanine aminotransferase increased
ECG QT corrected interval prolonged
Respiratory, thoracic and mediastinal disorders
Grade 1 2 3 4 5
Creelan BC et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.03

48. Depth and Duration of Response
OA05.03: Safety and Clinical Activity of Adoptive Cell Transfer Using Tumor Infiltrating Lymphocytes (TIL) Combined with Nivolumab in NSCLC – Creelan BC, et al
Key results (cont.)
Conclusions
The use of TILs in combination with nivolumab was well tolerated
Decreases in tumour size were observed with TIL, despite rapid progression on nivolumab
Depth and Duration of Response
Pre-TIL
Post-TIL
Nivolumab
TIL, IL2
Maintenance nivolumab PR
–60
–40
–20 20 40 60 80 PR
–80
–60
–40
–20 20 40 60 80 PD PD
Nivolumab
Nivolumab
TIL, IL2
% Change in tumour size vs. baseline
% Change in tumour size vs. pre-TIL
Time from first nivolumab, days
Time from TIL start, days 30 60 90
120
150
180 30 60 90
120
150
180
210
Creelan BC et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.03

49. OA05.05: Avelumab vs Docetaxel for Previously Treated Advanced NSCLC: Primary Analysis of the Phase 3 JAVELIN Lung 200 Trial – Barlesi F, et al
Study objective
To examine the efficacy and safety of avelumab compared with docetaxel in previously treated patients with advanced NSCLC
PD/ toxicity/ withdrawal
Avelumab 10 mg/kg q2w
(PD-L1+ n=264)
(All patients n=396)
Key patient inclusion criteria
Stage IIIB/IV NSCLC
PD after platinum doublet therapy
(n=792)
Stratification
PD-L1 status (PD-L1+ vs. PD-L1-)
Histology (squamous vs. nonsquamous) R
1:1
PD/ toxicity/ withdrawal
Docetaxel 75 mg/m2 q3w
(PD-L1+ n=265)
(All patients n=396)
Primary endpoint
OS in PD-L1+ population*
Secondary endpoints
OS (all patients), best overall response, PFS, QoL, safety
*Expression on ≥1% of tumour cells (PD-L1 IHC pharmDx)
Barlesi F et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.05

50. Time since treatment initiation, months
OA05.05: Avelumab vs Docetaxel for Previously Treated Advanced NSCLC: Primary Analysis of the Phase 3 JAVELIN Lung 200 Trial – Barlesi F, et al
Key results
OS in PD-L1+ population
Avelumab
(n=264)
Docetaxel
(n=265)
Median (95%CI), months
11.4 (9.4, 13.9)
10.3 (8.5, 13.0)
Stratified HR (96%CI)
0.90 (0.72, 1.12)
Stratified p-value (one-sided)
0.1627
Median follow-up, months (range)
18.9 (0.2–29.2)
17.8 (0.0–28.5)
100 80 60
OS, % 40 20
Avelumab
Docetaxel 3 6 9 12 15 18 21 24 27 30
Time since treatment initiation, months
No. at risk
Avelumab
264
218
172
150
109 73 52 29 16 5
Docetaxel
265
210
160
132 94 65 38 18 10 2
Barlesi F et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.05

51. OS in medium/high PD-L1+ subgroups (pre-planned analysis)
OA05.05: Avelumab vs Docetaxel for Previously Treated Advanced NSCLC: Primary Analysis of the Phase 3 JAVELIN Lung 200 Trial – Barlesi F, et al
Key results (cont.)
Conclusion
The primary endpoint was not met in the JAVELIN Lung 200 study – in pre-treated patients with advanced NSCLC whose tumours expressed PD-L1 at the ≥1% cut-off avelumab failed to improve OS compared with docetaxel
OS in medium/high PD-L1+ subgroups (pre-planned analysis)
≥50% PD-L1+
≥80% PD-L1+
Avelumab (n=168)
Docetaxel (n=147)
Median (95%CI), months
13.6 (10.1, 18.5)
9.2 (5.8, 12.4)
Unstratified HR (95%CI)
0.67 (0.51, 0.89)
Unstratified p-value (2-sided)
0.0052
Avelumab (n=120)
Docetaxel (n=106)
Median (95% CI), months
17.1 (10.6, 25.0)
9.3 (5.8, 13.1)
Unstratified HR (95% CI)
0.59 (0.42, 0.83)
Unstratified p-value (2-sided)
0.0022
100
100 80 80 60 60
OS, %
OS, % 40 40 20
Avelumab
Docetaxel 20
Avelumab
Docetaxel 3 6 9 12 15 18 21 24 27 30 3 6 9 12 15 18 21 24 27 30
No. at risk
Time since treatment initiation, months
Time since treatment initiation, months
Avelumab
168
145
117
102 76 52 38 23 12 4
120
105 85 77 59 43 31 21 12 4
Docetaxel
147
110 80 71 50 37 20 11 6 1
106 77 58 52 35 26 14 8 4
Barlesi F et al. J Thorac Oncol 2018;13(suppl):Abstr OA05.05

52. (n=46; interim analysis)
OA12.01: Phase II Data for the MET Inhibitor Tepotinib in Patients with Advanced NSCLC and MET Exon 14-Skipping Mutations – Felip E, et al
Study objective
To examine the efficacy and safety of tepotinib, an oral selective MET inhibitor, in patients with advanced NSCLC and MET exon 14-skipping mutations
Key patient inclusion criteria
Advanced/metastatic NSCLC
MET exon 14-skipping mutation positive by NGS
No EGFR activating mutations or ALK rearrangements
1L, 2L or 3L therapy
Tepotinib 500 mg/day
(n=46; interim analysis)
Primary endpoint
ORR (RECIST v1.1; independent review)
Secondary endpoints
Safety, ORR (investigator-assessed), DoR, PFS, OS
Felip E et al. J Thorac Oncol 2018;13(suppl):Abstr OA12.01

53. OA12.01: Phase II Data for the MET Inhibitor Tepotinib in Patients with Advanced NSCLC and MET Exon 14-Skipping Mutations – Felip E, et al
Key results
Conclusions
In this interim analysis tepotinib shows signs of activity in patients with advanced NSCLC with MET exon 14-­skipping mutations
Tepotinib was generally well tolerated; the most common side effects were peripheral oedema and diarrhoea, both were of mild to moderate intensity
L+ (n=24)
T+ (n=32)
Combined (n=40)
Response, n (%)
IRC
Investigator CR PR SD PD
Not evaluable
0 (0)
11 (45.8)
4 (16.7)
6 (25.0)
3 (12.5)
2 (8.3)
14 (58.3)
12 (37.5)
9 (28.1)
6 (18.8)
5 (15.6)
2 (6.3)
15 (46.9)
4 (12.5)
14 (35.0)
11 (27.5)
8 (20.0)
7 (17.5)
2 (5.0)
21 (52.5)
6 (15.0)
5 (12.5)
ORR, n (%) [95%CI]
11 (45.8) [25.6, 67.2]
16 (66.7)
[44.7, 84.4]
12 (37.5) [21.1, 56.3]
17 (53.1)
[34.7, 70.9]
14 (35.0) [20.6, 51.7]
23 (57.5)
[40.9, 73.0]
DCR, n (%) [95%CI]
15 (62.5) [40.6, 81.2]
18 (75.0)
[53.3, 90.2]
21 (65.5) [46.8, 81.4]
23 (71.9)
[53.3, 86.3]
25 (62.5) [45.8, 77.3]
29 (72.5)
[56.1, 85.4]
L+, positive in ctDNA; T+, positive in tumour; combined, positive in both ctDNA and tumour for MET mutations
Felip E et al. J Thorac Oncol 2018;13(suppl):Abstr OA12.01

54. SCLC, mesothelioma and thymic epithelial tumours
Other malignancies
SCLC, mesothelioma and thymic epithelial tumours

55. PL02.07: IMpower 133: Primary PFS, OS and Safety in a PH1/3 Study of 1L Atezolizumab + Carboplatin + Etoposide in Extensive-Stage SCLC – Liu SV, et al
Study objective
To evaluate the efficacy and safety of 1L atezolizumab or placebo in combination with carboplatin + etoposide in extensive-stage SCLC
Key patient inclusion criteria
Measureable extensive-stage SCLC
No prior systemic therapy
Treated asymptomatic brain metastases were eligible
ECOG PS 0–1
(n=403)
Atezolizumab 1200 mg IV q3w + carboplatin + etoposide
(n=201)
Atezolizumab maintenance
PD/ loss of benefit
Stratification
Sex (male vs. female)
ECOG PS (0 vs. 1)
Brain metastases (yes vs. no) R
1:1
Placebo + carboplatin + etoposide
(n=202)
Placebo
PD/ loss of benefit
Co-primary endpoints
OS, investigator-assessed PFS
Secondary endpoints
ORR, DoR and safety
Carboplatin AUC 5 mg/mL/min IV q3w; etoposide 100 mg/m2 IV D1–3 q3w
Liu SV et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.07

56. PL02.07: IMpower 133: Primary PFS, OS and Safety in a PH1/3 Study of 1L Atezolizumab + Carboplatin + Etoposide in Extensive-Stage SCLC – Liu SV, et al
Key results OS
Atezolizumab
+ CP/ET (n=201)
Placebo
+ CP/ET (n=202)
OS events, n (%)
104 (51.7)
134 (66.3)
Median OS, months (95%CI)
12.3 (10.8, 15.9)
10.3 (9.3, 11.3)
HR (95%CI)
0.70 (0.54, 0.91); p=0.0069
Median follow-up, months
13.9
100 80 60 40 20
12-month OS
51.7%
Overall survival, %
Atezolizumab + CP/ET
38.2%
Placebo + CP/ET +
Censored 2 4 6 8 10 12 14 16 18 20 22 24
Months
No. at risk
Atezolizumab
201
191
187
182
180
174
159
142
130
121
108 92 74 58 46 33 21 11 5 3 2 1
Placebo
202
194
189
186
183
171
160
146
131
114 96 81 59 36 27 13 8
From NEJM, Horn L, et al., First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer, DOI: /NEJMoa Copyright © (2018) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
Liu SV et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.07

57. Progression-free survival, %
PL02.07: IMpower 133: Primary PFS, OS and Safety in a PH1/3 Study of 1L Atezolizumab + Carboplatin + Etoposide in Extensive-Stage SCLC – Liu SV, et al
Key results (cont.)
Investigator-assessed PFS
Atezolizumab
+ CP/ET (N = 201)
Placebo
+ CP/ET (N = 202)
PFS events, n (%)
171 (85.1)
189 (93.6)
Median PFS, months (95%CI)
5.2 (4.4, 5.6)
4.3 (4.2, 4.5)
HR (95%CI)
0.77 (0.62, 0.96); p=0.017
Median follow-up, months
13.9 2 4 6 8 10 12 14 16 18 20 22 24
100 80 60 40
6-month PFS
Progression-free survival, %
30.9%
12-month PFS
Atezolizumab + CP/ET
Placebo + CP/ET
12.6% +
22.4%
Censored
5.4%
Months
No. at risk
Atezolizumab
201
190
178
158
147 98 58 48 41 32 29 26 21 15 12 11 3 2 1
Placebo
202
193
184
167 80 44 30 25 23 16 9 6 5
From NEJM, Horn L, et al., First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer, DOI: /NEJMoa Copyright © (2018) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
Liu SV et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.07

58. + carboplatin + etoposide + carboplatin + etoposide (n=130)
PL02.07: IMpower 133: Primary PFS, OS and Safety in a PH1/3 Study of 1L Atezolizumab + Carboplatin + Etoposide in Extensive-Stage SCLC – Liu SV, et al
Key results (cont.)
ORR
DoR CR
CR/PR SD PD 70 60 50 40 30 20 10
Atezolizumab + CP/ET
Placebo + CP/ET
Duration of response
Atezolizumab
+ carboplatin + etoposide
(n=121)
Placebo
+ carboplatin + etoposide (n=130)
Median duration, months (range)
4.2 (1.4–19.5)
3.9 (2.0–16.1)
HR (95%CI)
0.70 (0.53, 0.92)
6-month event-free rate, %
32.2
17.1
12-month event-free rate, %
14.9
6.2
Patients with ongoing response, n (%)
18 (14.9)
7 (5.4)
Response, %
Liu SV et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.07

59. PL02.07: IMpower 133: Primary PFS, OS and Safety in a PH1/3 Study of 1L Atezolizumab + Carboplatin + Etoposide in Extensive-Stage SCLC – Liu SV, et al
Key results (cont.)
Conclusions
In patients with extensive-stage SCLC, atezolizumab added to carboplatin + etoposide as 1L therapy demonstrated a clinically meaningful improvement in OS
There were no new safety findings for atezolizumab + carboplatin + etoposide and the incidence of immune-related AEs was similar to that seen with atezolizumab monotherapy
In patients with extensive-stage SCLC, atezolizumab + carboplatin + etoposide may be a potential new 1L SoC
Patients, n (%)
Atezolizumab + carboplatin + etoposide (n=198)
Placebo + carboplatin + etoposide (n=196)
Patients with ≥1 AE
198 (100)
189 (96.4)
Patients with ≥1 grade 3–4 AEs
133 (67.2)
125 (63.8)
Treatment-related AEs
188 (94.9)
181 (92.3)
Serious AEs
74 (37.4)
68 (34.7)
Immune-related AEs
79 (39.9)
48 (24.5)
AEs leading to withdrawal from any treatment
22 (11.1)
6 (3.1)
Treatment-related deaths
3 (1.5)
Liu SV et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.07

60. PL02.09: Nintedanib + Pemetrexed/Cisplatin in Patients with Unresectable MPM: Phase III Results from the LUME-Meso Trial – Scagliotti GV, et al
Study objective
To evaluate the efficacy and safety of nintedanib in combination with pemetrexed/cisplatin, followed by nintedanib maintenance, in patients with unresectable MPM
Nintedanib 200 mg bid* + pemetrexed/cisplatin**
(n=229)
Nintedanib maintenance
Key patient inclusion criteria
Histologically confirmed unresectable epithelioid MPM
Life expectancy ≥3 months
No previous systemic chemotherapy
(n=458) PD R
1:1
Placebo + pemetrexed/cisplatin**
(n=229)
Placebo PD
Primary endpoint
Investigator-assessed PFS
Secondary endpoints
OS, safety
*On D2–21; **500 mg/m2 and 75 mg/m2 IV q3w. Maximum treatment duration: 6 cycles
Scagliotti GV et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.09

61. PFS by investigator assessment
PL02.09: Nintedanib + Pemetrexed/Cisplatin in Patients with Unresectable MPM: Phase III Results from the LUME-Meso Trial – Scagliotti GV, et al
Key results
PFS by investigator assessment
100
Nintedanib
Placebo
PFS events, n (%)
126 (55)
124 (54)
Median PFS, months (95%CI)
6.8 (6.1, 7.0)
7.0 (6.7, 7.2)
HR (95%CI); p-value (two-sided)
1.01 (0.79, 1.30); p=0.914 80 60
Estimated percentage alive and progression-free
Independent central review confirmed findings:
HR 0.99 (95%CI 0.77, 1.28); p=0.963 40 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Time from randomisation, months
No. at risk
Nintedanib
229
213
190
162
158
129 86 57 44 28 15 13 9 5 2 1
Placebo
216
163
152
126 62 49 26 14 6 4 3
Scagliotti GV et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.09

62. PL02.09: Nintedanib + Pemetrexed/Cisplatin in Patients with Unresectable MPM: Phase III Results from the LUME-Meso Trial – Scagliotti GV, et al
Key results (cont.)
OS (interim analysis)
100
Post-study therapies were relatively balanced between arms 80 60
Estimated percentage alive
Nintedanib
Placebo
OS events, n (%)
64 (28)
63 (28)
Median OS, months (95%CI)
14.4
(12.2, 17.9)
16.1
(13.7, 19.3)
HR (95%CI); two-sided p-value
1.12 (0.79, 1.58); p=0.538 40 20 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Time from randomisation, months
No. at risk
Nintedanib
229
222
208
195
179
160
146
128
113 90 71 57 44 33 24 18 12 8 5 3 1
Placebo
226
215
196
185
165
143
127
110 99 77 65 53 32 25 19 15 10 4
Scagliotti GV et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.09

63. Overall frequency of AEs (group term)
PL02.09: Nintedanib + Pemetrexed/Cisplatin in Patients with Unresectable MPM: Phase III Results from the LUME-Meso Trial – Scagliotti GV, et al
Key results (cont.)
Conclusions
In patients with unresectable MPM, there was no difference in investigator-assessed PFS between nintedanib and placebo, which was confirmed by independent central review
The safety profile of nintedanib was consistent with previous findings
Overall frequency of AEs (group term)
AEs of any grade occurring more commonly with nintedanib and in ≥15% of patients
Grade: 1 2 ≥3
Nintedanib
Placebo
Patients, %
Nausea
Diarrhoea
Neutropenia
Vomiting
Infection
Electrolyte imbalance
Liver-related investigation
Rash
ALT increased
Abdominal pain
AST increased
Scagliotti GV et al. J Thorac Oncol 2018;13(suppl):Abstr PL02.09

64. OA08.03: Phase II Trial of Pembrolizumab (NCT ) In Previously-Treated Malignant Mesothelioma (MM): Final Analysis – Desai A, et al
Study objective
To examine the efficacy and safety of pembrolizumab in an unselected population of patients with mesothelioma, and to determine the optimal threshold for PD-L1 expression in correlation with tumour response
Key patient inclusion criteria
Histologically confirmed pleural or peritoneal mesothelioma
PD on/after pemetrexed and a platinum
≤2 prior cytotoxic regimens
Able to provide archival/fresh tissue
ECOG PS 0–1
(n=64)
Pembrolizumab 200 mg q3w
Primary endpoints
ORR in unselected and PD-L1+ populations
Optimal threshold for PD-L1 expression (22C3 IHC tumour cell/tumour proportion score [TPS])
Secondary endpoints
DCR, PFS and OS in unselected and PD-L1+ populations, proportion of patients with PD-L1 expression, toxicity
Desai A et al. J Thorac Oncol 2018;13(suppl):Abstr OA08.03

65. OA08.03: Phase II Trial of Pembrolizumab (NCT ) In Previously-Treated Malignant Mesothelioma (MM): Final Analysis – Desai A, et al
Key results
Conclusions
In patients with mesothelioma responses to pembrolizumab were observed regardless of PD-L1 expression
A higher response rate and longer PFS were seen in patients with high (≥50%) PD-L1 expression
PD-L1 expression may be a biomarker for predicting response to pembrolizumab in patients with mesothelioma
Unselected (n=64)
PR, n (%)
14 (22)
SD, n (%)
26 (41)
DCR, n (%)
40 (63)
Median DoR, months
11.7
Median PFS, months
4.1
Median OS, months
11.5
Outcomes by PD-L1 expression (PD-L1 TPS)
None
(0%)
(n=28)
Low
(1–49%)
(n=20)
High
(≥50%)
(n=14)
p-value
Response rate, % 7 25 43
0.021
Median PFS, months
2.8
4.1
4.9
0.034
Median OS, months
9.9 10
12.5
0.50
Desai A et al. J Thorac Oncol 2018;13(suppl):Abstr OA08.03