IASLC 19th World Conference on Lung Cancer

Transcription

1 Developed in association with the European Thoracic Oncology Platform IASLC 19th World Conference on Lung Cancer September Toronto, Canada Supported by Eli Lilly and Company. Eli Lilly and Company has not influenced the content of this publication

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 218. 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 etop@etop.eu-org. 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 218 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 PL2.5: 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 66,49 men and women aged 5 74 years identified from the registries Inclusion criteria included a smoking history >1 cigarettes/day for >3 years or >15 cigarettes/day for >25 years with smoking cessation 1 years 3,959 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 1 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 218;13(suppl):Abstr PL2.5

7 PL2.5: 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) 7 (.9) 36 Round 2 7,295 (92.3) 48 (6.6) 131 (1.8) 55 (.8) 42 Round 3 6,922 (87.6) 471 (6.8) 165 (2.4) 75 (1.1) 45 Round 4 5,279 (66.8) 11 (1.9) 15 (2.) 43 (.8) 41 Total 27,53 (85.6) 2,53 (9.3) 598 (2.2) 243 (.9) 41 De Koning HJ et al. J Thorac Oncol 218;13(suppl):Abstr PL2.5

8 Cumulative absolute number of first lung cancers PL2.5: 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 Control Screen 6% 5% 4% 3% 2% 1% Stage at diagnosis Netherlands cancer registry Control arm Screen arm Time since randomisation % Ia Ib II III IV Stage De Koning HJ et al. J Thorac Oncol 218;13(suppl):Abstr PL2.5

9 Cumulative lung cancer deaths PL2.5: 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.) 25 Cumulative lung cancer deaths (men only) Control arm: 214 lung cancer deaths Screen arm: 157 lung cancer deaths Years since randomisation De Koning HJ et al. J Thorac Oncol 218;13(suppl):Abstr PL2.5

10 PL2.5: 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.) Lung cancer mortality rate ratio (95%CI) Year 8 Year 9 Year 1 Males.75 (.59,.95);.76 (.6,.95);.74 (.6,.91); p=.15 p=.12 p=.3 Females.39 (.18,.78);.47 (.25,.84);.61 (.35, 1.4); p=.37) p=.69 p=.543 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 De Koning HJ et al. J Thorac Oncol 218;13(suppl):Abstr PL2.5

11 MA3.5: 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 6 new subsolid nodules that were not visible in retrospect were identified in 51 (.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 218;13(suppl):Abstr MA3.5

12 OA3.3: 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), 73-1 (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 218;13(suppl):Abstr OA3.3

13 OA3.3: 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 Assay Conclusions Aspirate (Mean, median) Biopsy (Mean, median) Resection (Mean, median) Aspirate vs. biopsy (p-value) Aspirate vs. resection (p-value) Biopsy vs. resection (p-value) 22C3 19., , , , , , , , , SP , 4.2,.4 6.8, SP , , , In PD-L1 IHC testing, Blueprint 2B reaffirms the data around assay performance and interobserver 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 Kerr KM et al. J Thorac Oncol 218;13(suppl):Abstr OA3.3

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

15 OA1.6: 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 Key patient inclusion criteria Locally advanced NSCLC Consolidation chemo** + atezolizumab 12 mg IV q3w x 2 cycles Part 2 Concurrent (n=4) Consolidation chemo** + atezolizumab 12 mg IV q3w x 2 cycles Primary endpoint Safety Part 1 Concurrent chemoradiation* (n=1) chemoradiation* + atezolizumab 12 mg q3w IV (n=3) *Carboplatin AUC2 + paclitaxel 5 mg/m 2 + radiation (6 66 Gy) q1w; **carboplatin AUC6 + paclitaxel 2 mg/m 2 q3w Secondary endpoints 1-year PFS, grade 3+ radiation pneumonitis, biomarker correlates of outcomes Maintenance atezolizumab up to 1 year Maintenance atezolizumab up to 1 year Lin LH et al. J Thorac Oncol 218;13(suppl):Abstr OA1.6

16 OA1.6: DETERRED: Phase II Trial Combining Atezolizumab Concurrently with Chemoradiation Therapy in Locally Advanced Non-Small Cell Lung Cancer Lin LH, et al Key results Part 1 (n=1) Part 2 (n=3) All AEs, n Grade 3+ AEs, n Patients with grade 3+, n (%) 6 (6) 17 (57) AEs leading to withdrawal, n (%) 3 (3) 3 (1) Patients with atezolizumab grade 3+ AEs, n (%) 3 (3) 7 (23) 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 Lin LH et al. J Thorac Oncol 218;13(suppl):Abstr OA1.6

17 Percent survival Percent survival OA1.6: 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.) Early preliminary efficacy results Median follow-up 1.3 years for part 1,.75 years for part 2 1 PFS Part 1 Part 2 1 OS Part 1 Part Conclusions Time, months Time, months Median PFS, months 1-year PFS Median OS, months 1-year OS Part Part 2 NR 66 NR 7 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 Lin LH et al. J Thorac Oncol 218;13(suppl):Abstr OA1.6

18 OA2.1: 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 6 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 218;13(suppl):Abstr OA2.1

19 PFS by BICR, % OA2.1: 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 Response, n (%) ORR, n (%) [95%CI] CNS disease at baseline (n=23) 17 (73.9) [51.6, 89.8] No CNS disease at baseline (n=3) 24 (8.) [61.4, 92.3] CR 3 (1.) PR 17 (73.9) 21 (7.) SD 1 (3.3) PD 4 (17.4) Non-CR/PD 3 (1.) Missing/unevaluable 2 (8.7) 2 (6.7) CBR, n (%) [95%CI] 41 (77.4) [63.8, 87.7] month event-free probability: PFS No. Time, months at risk Total Censored Median (95%CI) Total [N=53]: 19 [12.2, 36.6] 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 Doebele RC et al. J Thorac Oncol 218;13(suppl):Abstr OA2.1

20 MA4.9: 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) Key patient inclusion criteria Stage IB IIIB resectable NSCLC (n=54 of 18 planned) Atezolizumab 12 mg D1, 22 2 cycles Surgical resection SoC adjuvant therapy Clinical benefit Atezolizumab 12 mg q3w for 12 months Primary endpoint MPR Secondary endpoints Safety, response by PD-L1, OS, DFS Rusch VW et al. J Thorac Oncol 218;13(suppl):Abstr MA4.9

21 Pathologic regression Regression, % (%) MA4.9: Neoadjuvant Atezolizumab in Resectable Non-Small Cell Lung Cancer (NSCLC): Updated Results from a Multicenter Study (LCMC3) Rusch VW, et al Key results Outcome MPR, n (%) [95%CI] Efficacy population (n=45) 1 (22) [11, 37] pcr, n (%) 3 (7) ORR, n (%) PR 3 (7) SD 42 (93) PD RECIST response Tobacco use Histology RECIST response: Tobacco use: Histology: PR SD Never Current Previous Non-squamous Squamous MPR is defined as 1% viable tumour cells PD-L1 expression: TC1/2/3 or IC1/2/3 TC and IC Unknown Rusch VW et al. J Thorac Oncol 218;13(suppl):Abstr MA4.9

22 MA4.9: 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 Incidence, n (%) 1 AE Grade 3 4 Grade 5 Treatment related AE Grade 3 4 Safety population (n=54) 51 (94) 15 (28) 1* (2) 32 (59) 3 (6) Serious AE 16 (3) AE leading to withdrawal 2 (4) *Sudden death not related to study treatment, approximately 2 weeks after surgery 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 Rusch VW et al. J Thorac Oncol 218;13(suppl):Abstr MA4.9

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

24 PL2.3: 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 Key patient inclusion criteria Stage IIIB/IV ALK+ NSCLC No prior ALK inhibitor 1 prior systemic therapy (n=275) R 1:1 Brigatinib 18 mg/day (7-day lead-in at 9 mg) (n=137) Stratification Brain metastases (yes vs. no) Prior chemotherapy (yes vs. no) Crizotinib 25 mg bid* (n=138) PD/ toxicity/ other PD/ toxicity/ other Primary endpoint BIRC-assessed PFS (RECIST v1.1) Secondary endpoints ORR, intracranial ORR, intracranial PFS, OS, safety *Crossover to brigatinib permitted at PD Camidge R et al. J Thorac Oncol 218;13(suppl):Abstr PL2.3

25 PFS, % of patients PL2.3: 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 8 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., 12.9) 43 (32, 53) HR for disease progression or death.49 (95%CI.33,.74); p=.7 by log-rank test Brigatinib (n=137) Crizotinib (n=138) Time, months 1-year OS probability: brigatinib 85% (95%CI 76, 91); crizotinib 86% (95%CI 77, 91) From NEJM, Camidge R, et al., Brigatinib versus Crizotinib in ALK-positive non small-cell lung cancer, DOI:1.156/NEJMoa Copyright (218) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. Camidge R et al. J Thorac Oncol 218;13(suppl):Abstr PL2.3

26 Intracranial PFS, % of patients PL2.3: 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 1 8 Treatment Median intracranial PFS, mths (95%CI) 1-Year PFS, % (95%CI) Brigatinib NR (11., NR) 67 (47, 8) Crizotinib 5.6 (4.1, 9.2) 21 (6, 42) HR.27 (95%CI.13,.54); p<.1 by log-rank test Brigatinib (n=43) Crizotinib (n=47) Time, months From NEJM, Camidge R, et al., Brigatinib versus Crizotinib in ALK-positive non small-cell lung cancer, DOI:1.156/NEJMoa Copyright (218) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. Camidge R et al. J Thorac Oncol 218;13(suppl):Abstr PL2.3

27 PL2.3: 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 218;13(suppl):Abstr PL2.3

28 OA5.7: 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 Key patient inclusion criteria Stage IV non-squamous NSCLC Chemotherapy naïve Without EGFR or ALK genetic alterations (n=578) R 1:1 Atezolizumab* + carboplatin/ cisplatin + pemetrexed** (4 or 6 cycles) (n=292) Stratification Sex Smoking status ECOG PS Chemotherapy regimen Carboplatin/cisplatin + pemetrexed** (4 or 6 cycles) (n=286) Atezolizumab + pemetrexed maintenance Pemetrexed maintenance PD/ loss of benefit PD/ loss of benefit Co-primary endpoints Investigator-assessed PFS, OS *Atezolizumab 12 mg IV q3w; **carboplatin AUC6 mg/ml/min IV q3w or cisplatin 75 mg/m 2 IV q3w + pemetrexed 5 mg/m 2 IV q3w Secondary endpoints Investigator-assessed ORR and DoR, PRO and safety Papadimitrakopoulou VA et al. J Thorac Oncol 218;13(suppl):Abstr OA5.7

29 Progression-free survival, % OA5.7: IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC Papadimitrakopoulou VA, et al Key results 1 Investigator-assessed PFS HR.6 (95%CI.49,.72); p<.1 Minimum follow-up, 11.7 months Median follow-up, 14.8 months 8 6 Atezolizumab + carboplatin/cisplatin + pemetrexed Carboplatin/cisplatin + pemetrexed months (95%CI 4.3, 5.6) months (95%CI 6.6, 8.5) No. at risk Atezolizumab + C + P C + P Time, months Papadimitrakopoulou VA et al. J Thorac Oncol 218;13(suppl):Abstr OA5.7

30 Overall survival, % OA5.7: 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 1 8 HR.81 (95%CI.64, 1.3); p=.797 Minimum follow-up: 11.7 months Median follow-up: 14.8 months Atezolizumab + carboplatin/cisplatin + pemetrexed Carboplatin/cisplatin + pemetrexed) months (95%CI 11.4, 15.5) months (95%CI 13., NE) No. at risk Atezolizumab + C + P C + P Time, months Data cutoff: May 22, 218 Papadimitrakopoulou VA et al. J Thorac Oncol 218;13(suppl):Abstr OA5.7

31 OA5.7: IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC Papadimitrakopoulou VA, et al Key results (cont.) All-cause AEs, n (%) Grade 3 4 Grade 5 Conclusions Atezolizumab + carboplatin/ cisplatin + pemetrexed (n=291) 286 (98) 181 (62) 21 (7) Carboplatin/cisplatin + pemetrexed (n=274) 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) 14 (38) 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 Papadimitrakopoulou VA et al. J Thorac Oncol 218;13(suppl):Abstr OA5.7

32 OA7.1: 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 Key patient inclusion criteria NSCLC Up to 4 metastases (any site) No limit on prior therapies No PD-(L)1 therapies PS 1 (n=45) Locally ablative therapy to all known sites of disease SD or better Pembrolizumab 2 mg q3w for 6 months PD or patient preference Pembrolizumab 2 mg q3w for 6 months Off study Primary endpoints PFS, safety Secondary endpoints OS, QoL Bauml JM et al. J Thorac Oncol 218;13(suppl):Abstr OA7.1

33 Probability Probability OA7.1: 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 1..8 Progression-free survival Median PFS: 19.1 months (95%CI 11.5, 26.7) 1..8 Overall survival Median OS: NR (95%CI not defined) No. at risk Months from start of definitive therapy No. at risk Months from start of definitive therapy 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 Bauml JM et al. J Thorac Oncol 218;13(suppl):Abstr OA7.1

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

35 PL2.1: 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 1 (n=713) R 2:1 Durvalumab 1 mg/kg q2w for up to 12 months (n=476) Stratification Sex Age Smoking history 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 218;13(suppl):Abstr PL2.1

36 Probability of OS PL2.1: 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) 66.3% HR.68 (99.73%CI.469,.997); p= % % No. at risk Durvalumab Placebo Time from randomisation, months From NEJM, Antonia SJ, et al., Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC, DOI:1.156/NEJMoa Copyright (218) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. Antonia SJ et al. J Thorac Oncol 218;13(suppl):Abstr PL2.1

37 Probability of PFS PL2.1: Overall Survival with Durvalumab Versus Placebo After Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC Antonia SJ, et al Key results (cont.) 1. 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.) 5.6 (4.6, 7.7) % HR.51 (95%CI.41,.63) % % 26.7% No. at risk Durvalumab Placebo Time from randomisation, months From NEJM, Antonia SJ, et al., Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC, DOI:1.156/NEJMoa Copyright (218) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. Antonia SJ et al. J Thorac Oncol 218;13(suppl):Abstr PL2.1

38 Probability of death or distant metastasis PL2.1: Overall Survival with Durvalumab Versus Placebo After Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC Antonia SJ, et al Key results (cont.) Updated time to death or distant metastasis (TTDM) by BICR (ITT) Incidence of new lesions by BICR (ITT) No. at risk Durvalumab Placebo Time from randomisation, months Median TTDM, months (95%CI) Durvalumab 28.3 (24., 34.9) Placebo 16.2 (12.5, 21.1) TTDM HR.53 (95%CI.41,.68) Site, n (%) Durvalumab (n=476) Placebo (n=237) Any new lesion 17 (22.5) 8 (33.8) Lung 6 (12.6) 44 (18.6) Lymph nodes 31 (6.5) 27 (11.4) Brain 3 (6.3) 28 (11.8) Liver 9 (1.9) 8 (3.4) Bone 8 (1.7) 7 (3.) Adrenal 3 (.6) 5 (2.1) Other 1 (2.1) 5 (2.1) From NEJM, Antonia SJ, et al., Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC, DOI:1.156/NEJMoa Copyright (218) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. Antonia SJ et al. J Thorac Oncol 218;13(suppl):Abstr PL2.1

39 PL2.1: Overall Survival with Durvalumab Versus Placebo After Chemoradiotherapy in Stage III NSCLC: Updated Results from PACIFIC Antonia SJ, et al Key results (cont.) Conclusions Durvalumab (n=475) Placebo (n=234) Any-grade all-causality AEs, n (%) 46 (96.8) 222 (94.9) Grade 3/4 145 (3.5) 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) Grade 3/4 17 (3.6) 7 (3.) Outcome of death 5 (1.1) 5 (2.1) Leading to discontinuation 3 (6.3) 1 (4.3) 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 Antonia SJ et al. J Thorac Oncol 218;13(suppl):Abstr PL2.1

40 OA2.6: A Phase II Trial of Poziotinib in EGFR and HER2 exon 2 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 T79M) and HER2 exon 2 Key patient inclusion criteria Metastatic NSCLC Cohort 1: EGFR exon 2 mutant (except acquired T79M) Cohort 2: HER2 exon 2 mutations/insertions Unlimited prior systemic or targeted therapies (n=5) Primary endpoint ORR (RECIST v1.1) Poziotinib 16 mg/day PO (dose reductions to 12 or 8 mg permitted) Secondary endpoints PFS, OS, DCR, DoR, safety PD/death/ toxicity Heymach JV et al. J Thorac Oncol 218;13(suppl):Abstr OA2.6

41 Percent survival Percent survival OA2.6: A Phase II Trial of Poziotinib in EGFR and HER2 exon 2 Mutant Non- Small Cell Lung Cancer (NSCLC) Heymach JV, et al Key results The ORR was 55% and 5% in patients with EGFR and HER2 exon 2 mutant NSCLC, respectively 1 75 PFS in ITT population Median PFS 5.5 months (95%CI 5.2, NA) 1 PFS in HER2 cohort (n=13) Median PFS 5.1 months 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 Months Months In heavily pre-treated patients with metastatic EGFR or HER2 exon 2 mutant NSCLC, poziotinib demonstrated anti-tumour activity and the EGFR-related AEs were manageable Heymach JV et al. J Thorac Oncol 218;13(suppl):Abstr OA2.6

42 MA4.2: 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 Key patient inclusion criteria NSCLC Pre-treated (n=34) Pegilodecakin 1 2 mg/day SC + pembrolizumab 2 mg/kg IV q3w or nivolumab 3 mg/kg IV q2w Primary endpoint ORR (RECIST v1.1) Secondary endpoints PFS, OS, DCR, safety Garon EB et al. J Thorac Oncol 218;13(suppl):Abstr MA4.2

43 MA4.2: Responses and Durability in NSCLC Treated With Pegilodecakin and Anti-PD-1 Garon EB, et al Key results Population (n=evaluable/enrolled) mpfs, months mos, months ORR, % DCR, % Pegilodecakin (n=7/9) Pegilodecakin + nivolumab (n=22/29) NR NR Pegilodecakin + pembrolizumab (n=5/5) Pegilodecakin + anti-pd-1 (n=27/34 pooled) NR NR PD-L1 negative (<1%; n=12) 5.7 NR PD-L1 low (1 49%; n=3) 8.9 NR PD-L1 high ( 5%; n=5) 1.7 NR 8 1 TMB low ( 243 mut/exome; n=8) 1.3 NR 63 1 TMB high (>243 mut/exome; n=2) Liver metastases (n=8) Grade 3 4 AEs occurring in 5% of patients included anaemia (17%), thrombocytopenia (17%), fatigue (17%), hypertriglyceridaemia (1%), 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 Garon EB et al. J Thorac Oncol 218;13(suppl):Abstr MA4.2

44 OA5.1: 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) Primary endpoint ORR (irrecist) Entinostat 5 mg PO q1w + pembrolizumab 2 mg IV q3w Secondary endpoints PFS, OS, safety PD/ death/ toxicity Hellmann MD et al. J Thorac Oncol 218;13(suppl):Abstr OA5.1

45 Change from baseline, % OA5.1: 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 1% (7/72 patient, 95%CI 4, 19) Median DoR was 5.3 months PD SD PR Confirmed 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 Hellmann MD et al. J Thorac Oncol 218;13(suppl):Abstr OA5.1

46 OA5.3: 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) Primary endpoint Safety/tolerability *IL-2 intermediate dose:18 miu/m 2 over 6, 12 and 24 hours then 4.5 miu/m 2 over 24 hours x 3) on D1 6 Resection of lesion for TIL manufacture; nivolumab 24 mg q2w, 4 doses PR/ clinical benefit PD/SD Nivolumab q4w for 1 year Cyclophosphamide 6 mg/kg + Mesna D 7, 6 then fludarabine 25 mg/m 2 D 5 to 1; D TIL infusion ( CD3+ cells); IL-2 IV* until D6; nivolumab 48 mg q4w from D29 up to 1 year Secondary endpoints Efficacy, PK, PD, tumour proteomics, whole exome sequencing, transcriptomics Creelan BC et al. J Thorac Oncol 218;13(suppl):Abstr OA5.3

47 Lymphocyte count decreased White blood cell decreased Anaemia Hypophosphatemia Hypoalbuminemia Neutrophil count decreased Platelet count decreased Hyponatremia Fever Hypocalcemia Nausea Aspartate aminotransferase increased Alanine aminotransferase increased Alkaline phosphatase increased Hypoxia Diarrhoea Hypotension Sinus tachycardia Hyperkalemia INR increased Anorexia Dehydration Dysphagia Dyspnoea Chills Hypermagnesemia Pulmonary oedema Creatinine increased Acute kidney injury Dizziness Oedema limbs Gastritis Hypothyroidism Vomiting Hypokalemia Pruritus Rash acneiform Stroke Hyperglycaemia Lung infection Confusion Hypertension Infections and infestations Non-cardiac chest pain Pain Respiratory, thoracic and mediastinal disorders Urinary tract infection Weight loss Abdominal pain Blood bilirubin increased Conjunctivitis Constipation Depression Dry eye Dry mouth Dry skin Dysgeusia ECG QT corrected interval prolonged Genital oedema Headache Hypernatremia Hypomagnesemia Menorrhagia Mucositis oral Tremor Urinary incontinence Urinary urgency Hypernatremia Urticaria Wheezing Worst grade event, % OA5.3: Safety and Clinical Activity of Adoptive Cell Transfer Using Tumor Infiltrating Lymphocytes (TIL) Combined with Nivolumab in NSCLC Creelan BC, et al Key results 1 AEs attributed to any treatment post-til AEs associated with cyclophosphamide, fludarabine, TIL and/or IL-2 (n=1) 2 Grade Creelan BC et al. J Thorac Oncol 218;13(suppl):Abstr OA5.3

48 % Change in tumour size vs. baseline % Change in tumour size vs. pre-til OA5.3: 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.) Pre-TIL Depth and Duration of Response Post-TIL 8 6 Nivolumab PR PD Nivolumab 8 6 TIL, IL2 Maintenance nivolumab PR PD Nivolumab 4 TIL, IL Time from first nivolumab, days Time from TIL start, days 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 Creelan BC et al. J Thorac Oncol 218;13(suppl):Abstr OA5.3

49 OA5.5: Avelumab vs Docetaxel for Previously Treated Advanced NSCLC: Primary Analysis of the Phase 3 JAVELIN Lung 2 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 Key patient inclusion criteria Stage IIIB/IV NSCLC PD after platinum doublet therapy (n=792) R 1:1 Avelumab 1 mg/kg q2w (PD-L1+ n=264) (All patients n=396) Stratification PD-L1 status (PD-L1+ vs. PD-L1-) Histology (squamous vs. nonsquamous) Docetaxel 75 mg/m 2 q3w (PD-L1+ n=265) (All patients n=396) PD/ toxicity/ withdrawal PD/ toxicity/ withdrawal 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 73-1 pharmdx) Barlesi F et al. J Thorac Oncol 218;13(suppl):Abstr OA5.5

50 OS, % OA5.5: Avelumab vs Docetaxel for Previously Treated Advanced NSCLC: Primary Analysis of the Phase 3 JAVELIN Lung 2 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) 1.3 (8.5, 13.) Stratified HR (96%CI).9 (.72, 1.12) Stratified p-value (one-sided).1627 Median follow-up, months (range) 18.9 ( ) 17.8 (. 28.5) 4 No. at risk Avelumab Docetaxel 2 Avelumab Docetaxel Time since treatment initiation, months Barlesi F et al. J Thorac Oncol 218;13(suppl):Abstr OA5.5

51 OS, % OS, % OA5.5: Avelumab vs Docetaxel for Previously Treated Advanced NSCLC: Primary Analysis of the Phase 3 JAVELIN Lung 2 Trial Barlesi F, et al Key results (cont.) 1 8 OS in medium/high PD-L1+ subgroups (pre-planned analysis) 5% PD-L1+ Avelumab (n=168) Docetaxel (n=147) Median (95%CI), months 13.6 (1.1, 18.5) 9.2 (5.8, 12.4) Unstratified HR (95%CI).67 (.51,.89) Unstratified p-value (2-sided) % PD-L1+ Avelumab (n=12) Docetaxel (n=16) Median (95% CI), months 17.1 (1.6, 25.) 9.3 (5.8, 13.1) Unstratified HR (95% CI).59 (.42,.83) Unstratified p-value (2-sided) Avelumab Docetaxel No. Time since treatment initiation, months at risk Avelumab Docetaxel Time since treatment initiation, months Conclusion The primary endpoint was not met in the JAVELIN Lung 2 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 2 Avelumab Docetaxel Barlesi F et al. J Thorac Oncol 218;13(suppl):Abstr OA5.5

52 OA12.1: 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 5 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 218;13(suppl):Abstr OA12.1

53 OA12.1: 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 L+ (n=24) T+ (n=32) Combined (n=4) Response, n (%) IRC Investigator IRC Investigator IRC Investigator CR () 2 (8.3) () 2 (6.3) () 2 (5.) PR 11 (45.8) 14 (58.3) 12 (37.5) 15 (46.9) 14 (35.) 21 (52.5) SD 4 (16.7) 2 (8.3) 9 (28.1) 6 (18.8) 11 (27.5) 6 (15.) PD Not evaluable 6 (25.) 3 (12.5) 3 (12.5) 3 (12.5) 6 (18.8) 5 (15.6) 5 (15.6) 4 (12.5) 8 (2.) 7 (17.5) 5 (12.5) 6 (15.) 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, 7.9] 14 (35.) [2.6, 51.7] 23 (57.5) [4.9, 73.] DCR, n (%) [95%CI] 15 (62.5) [4.6, 81.2] 18 (75.) [53.3, 9.2] 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] 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+, positive in ctdna; T+, positive in tumour; combined, positive in both ctdna and tumour for MET mutations Felip E et al. J Thorac Oncol 218;13(suppl):Abstr OA12.1

54 Other malignancies SCLC, mesothelioma and thymic epithelial tumours

55 PL2.7: 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 extensivestage SCLC Atezolizumab 12 mg IV q3w + carboplatin + etoposide (n=21) Atezolizumab maintenance PD/ loss of benefit No prior systemic therapy Treated asymptomatic brain metastases were eligible ECOG PS 1 (n=43) R 1:1 Stratification Sex (male vs. female) ECOG PS ( vs. 1) Brain metastases (yes vs. no) Placebo + carboplatin + etoposide (n=22) 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 1 mg/m 2 IV D1 3 q3w Liu SV et al. J Thorac Oncol 218;13(suppl):Abstr PL2.7

56 Overall survival, % PL2.7: 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=21) Placebo + CP/ET (n=22) OS events, n (%) 14 (51.7) 134 (66.3) Median OS, months (95%CI) 12.3 (1.8, 15.9) 1.3 (9.3, 11.3) HR (95%CI) 12-month OS 51.7%.7 (.54,.91); p=.69 Median follow-up, months % No. at risk Months Atezolizumab Placebo Atezolizumab + CP/ET Placebo + CP/ET Censored From NEJM, Horn L, et al., First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer, DOI:1.156/NEJMoa Copyright (218) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. Liu SV et al. J Thorac Oncol 218;13(suppl):Abstr PL2.7

57 Progression-free survival, % PL2.7: 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.) 1 8 Investigator-assessed PFS Atezolizumab + CP/ET (N = 21) Placebo + CP/ET (N = 22) 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).77 (.62,.96); p=.17 Median follow-up, months month PFS % 22.4% Months 12-month PFS 12.6% 5.4% No. at risk Atezolizumab Placebo Atezolizumab + CP/ET Placebo + CP/ET Censored From NEJM, Horn L, et al., First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer, DOI:1.156/NEJMoa Copyright (218) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. Liu SV et al. J Thorac Oncol 218;13(suppl):Abstr PL2.7

58 Response, % PL2.7: 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 Atezolizumab + CP/ET Placebo + CP/ET Duration of response Median duration, months (range) Atezolizumab + carboplatin + etoposide (n=121) 4.2 ( ) Placebo + carboplatin + etoposide (n=13) 3.9 ( ) CR CR/PR SD PD HR (95%CI).7 (.53,.92) 6-month event-free rate, % month event-free rate, % Patients with ongoing response, n (%) 18 (14.9) 7 (5.4) Liu SV et al. J Thorac Oncol 218;13(suppl):Abstr PL2.7

59 PL2.7: 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.) Patients, n (%) Conclusions Atezolizumab + carboplatin + etoposide (n=198) Placebo + carboplatin + etoposide (n=196) Patients with 1 AE 198 (1) 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) 3 (1.5) 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 Liu SV et al. J Thorac Oncol 218;13(suppl):Abstr PL2.7

60 PL2.9: 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 Key patient inclusion criteria Histologically confirmed unresectable epithelioid MPM Life expectancy 3 months R 1:1 Nintedanib 2 mg bid* + pemetrexed/cisplatin** (n=229) Nintedanib maintenance PD No previous systemic chemotherapy (n=458) Placebo + pemetrexed/cisplatin** (n=229) Placebo PD Primary endpoint Investigator-assessed PFS *On D2 21; **5 mg/m 2 and 75 mg/m 2 IV q3w. Maximum treatment duration: 6 cycles Secondary endpoints OS, safety Scagliotti GV et al. J Thorac Oncol 218;13(suppl):Abstr PL2.9

61 Estimated percentage alive and progression-free PL2.9: 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 1 Nintedanib Placebo PFS events, n (%) 126 (55) 124 (54) Median PFS, months (95%CI) 6.8 (6.1, 7.) 7. (6.7, 7.2) HR (95%CI); p-value (two-sided) 1.1 (.79, 1.3); p=.914 Independent central review confirmed findings: HR.99 (95%CI.77, 1.28); p= No. at risk Time from randomisation, months Nintedanib Placebo Scagliotti GV et al. J Thorac Oncol 218;13(suppl):Abstr PL2.9

62 Estimated percentage alive PL2.9: Nintedanib + Pemetrexed/Cisplatin in Patients with Unresectable MPM: Phase III Results from the LUME-Meso Trial Scagliotti GV, et al Key results (cont.) 1 8 OS (interim analysis) Post-study therapies were relatively balanced between arms Nintedanib Placebo OS events, n (%) 64 (28) 63 (28) Median OS, months (95%CI) HR (95%CI); two-sided p-value 14.4 (12.2, 17.9) 16.1 (13.7, 19.3) 1.12 (.79, 1.58); p= Time from randomisation, months No. at risk Nintedanib Placebo Scagliotti GV et al. J Thorac Oncol 218;13(suppl):Abstr PL2.9

63 Patients, % PL2.9: Nintedanib + Pemetrexed/Cisplatin in Patients with Unresectable MPM: Phase III Results from the LUME-Meso Trial Scagliotti GV, et al Key results (cont.) Conclusions Overall frequency of AEs (group term) AEs of any grade occurring more commonly with nintedanib and in 15% of patients Nausea Diarrhoea Neutropenia Vomiting Infection Electrolyte imbalance Grade: Nintedanib Placebo Liver-related investigation 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 Rash ALT increased Abdominal pain AST increased Scagliotti GV et al. J Thorac Oncol 218;13(suppl):Abstr PL2.9

64 OA8.3: 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 1 (n=64) Pembrolizumab 2 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 218;13(suppl):Abstr OA8.3