Immunotherapeutic Approaches in the Treatment of NSCLC. Keith Kerr, MBChB, FRCPath. Aberdeen Royal Infirmary

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1 01 Immunotherapeutic Approaches in the Treatment of NSCLC Keith Kerr, MBChB, FRCPath. Aberdeen Royal Infirmary

2 Outline 02 Review the concept and evolution of immunotherapy in the treatment of cancer Discuss current immunotherapeutic approaches involving checkpoint inhibitions in the treatment of NSCLC Discuss additional immunotherapeutic approaches being evaluated in the treatment of NSCLC

3 Development of Immunotherapy in the Treatment of Cancer Timeline: The history of cancer immunotherapy 03 Description of immune infiltrates in tumours by Virchow First report of allogeneic bone marrow transplantation Hypothesis of cancer immunosurveillance by Burnet Discovery of MHCIrestricted CD8+ T cell recognition by Zinkernagel and Doherty First study with IL-2 First study with IFNα in melanoma First study with adoptive cell transfer in cancer First study of isolated limb perfusion with TNF in melanoma and sarcoma Rediscovery of the regulatory T cell by Sakaguchi Non-myeloablative chemotherapies and adoptive T cell transfer in melanoma HPV vaccination in VIN FDA approved pembrolizumab and nivolumab for the treatment of melanoma Treatment of cancer with bacterial products by Coley Discovery of crosspresentation by Bevan Key regulators of T-cell response are elucidated FDA approval of sipuleucel-t in prostate cancer and ipilimumab in melanoma Discovery of the dendritic cells by Steinman First study with BCG in bladder cancer (1991, 1994) Characterisation of human TAAs by Rosenberg and Boon ( ,2000) Discovery of the immunological function of TLR FDA approved nivolumab for the treatment of squamous NSCLC Remains an active area of research TAA = Tumour-associated antigen; VIN = Vulvar intraepithelial neoplasia; TLR = Toll-like receptor; BCG = Bacille Calmette-Guerin. 1. Lesterhuis WJ et al. Nat Rev Drug Discov. 2011;10: ;

4 The Concept of Immune Surveillance and Escape 04 Schreiber RD et al. Science. 2011;25:331:

5 Key Regulators of Cytotoxic T Lymphocyte Response 05 Cytotoxic T cell responses are regulated by multiple costimulatory and inhibitory interactions Pardoll DM et al. Nat Rev Cancer. 2012;12:

6 Immune Checkpoint Inhibition in the Treatment of Cancer: MOAs of Anti-CTLA-4 and Anti-PD-1/PD-L1 Agents 06 Ipilimumab Ribas A. N Engl J Med. 2012;366: Nivolumab Pembrolizumab MPDL3280A MEDI4736 Immune checkpoints play an important role in suppressing the body s antitumour response

7 PD-1/PD-L1 Inhibition in the Treatment of NSCLC 07 Phase 3 data: Nivolumab in non-squamous (CheckMate 057) and squamous cell (CheckMate 017) lung cancer Phase 2 data: Atezolizumab in NSCLC (POPLAR trial) Phase 1 data: Pembrolizumab in NSCLC (KEYNOTE 001 trial)

8 CheckMate-057: Phase 3 Trial of Nivolumab vs Docetaxel in Patients With Non-Squamous NSCLC 08 Stage IIIb/IV non-squamous NSCLC Failed one prior platinum-based doublet Prior TKI therapy allowed for known ALK translocation or EGFR mutation Prior maintenance therapy allowed ECOG PS: 0-1 Maintenance therapy included pemetrexed, bevacizumab or erlotinib (not considered a separate line of therapy) Endpoints: Paz-Ares L et al. J Clin Oncol. 2015;33:(suppl; Abstract LBA109). N=582 n=292 n=290 Nivolumab: 3 mg/kg IV Q2Wk Docetaxel: 75 mg/m 2 IV Q3Wk Patients stratified by prior maintenance therapy and line of therapy (2 nd vs 3 rd -line) Primary: OS Secondary: ORR, PFS, correlation between PD-L1 expression and efficacy PD-L1 expression measured using the Dako/BMS automated IHC assay R 1:1 Fully validated with analytical performance having met all pre-determined acceptance criteria for sensitivity, specificity, precision, and robustness Until PD or unacceptable toxicity

9 CheckMate-057: Baseline Characteristics 09 Median age, years (range) 75, % Nivolumab n= (37-84) 7 Docetaxel n= (21-85) 8 Male, % Smoking status, % Current/former smoker Never smoker ECOG PS, % 0 1 Prior maintenance therapy, % No. of prior systemic therapy, % 1 2 EGFR-positive mutation status, % ALK-positive translocation status, % 4 3 Baseline PD-L1 expression, quantifiable (% of evaluable patients) 1% 5% 10% Not quantifiable (% of randomised patients) % (455/582) of randomised patients had quantifiable PD-L1 expression. Baseline expression was well balanced between nivolumab and docetaxel Paz-Ares L et al. J Clin Oncol. 2015;33:(suppl; Abstract LBA109).

10 CheckMate-057: OS (Primary Endpoint) 010 OS (%) yr OS rate = 39% Nivolumab n= Time (months) Docetaxel n=290 mos, mo HR = 0.73 (96% CI: 0.59, 0.89), P= yr OS rate = 51% Nivolumab Docetaxel Number of patients at risk Nivolumab Docetaxel Symbols represent censored observations. CI = confidence interval; HR = hazard ratio. Paz-Ares L et al. J Clin Oncol. 2015;33:(suppl; Abstract LBA109).

11 CheckMate-057: PFS 011 Symbols represent censored observations. Paz-Ares L et al. J Clin Oncol. 2015;33:(suppl; Abstract LBA109).

12 CheckMate-057: OS and PFS Hazard Ratios by Baseline PD-L1 Expression 012 a Interaction P-value from Cox proportional hazard model with treatment, PD-1 expression and treatment by PC-L1 expression interaction. Paz-Ares L et al. J Clin Oncol. 2015;33:(suppl; Abstract LBA109).

13 CheckMate-017: Phase 3 Trial of Nivolumab vs Docetaxel in Squamous NSCLC 013 Second-line, stage IIIb/IV squamous NSCLC Failed one prior platinumbased doublet ECOG PS: 0-1 R 1:1 n=135 n=137 Nivolumab: 3 mg/kg IV Q2Wk Docetaxel: 75 mg/m 2 IV Q3Wk Until PD or unacceptable toxicity Endpoints: Primary: OS Secondary: ORR, PFS, correlation between PD-L1 expression and efficacy Spigel D et al. J Clin Oncol. 2015;33:(suppl; Abstract 8009). N=272 Patients stratified by region and prior paclitaxel use One pre-planned interim analysis for OS The boundary for declaring superiority of OS at the pre-planned interim analysis was P<0.03

14 CheckMate-017: Baseline Characteristics 014 Median age, years (range) 75, % Nivolumab n= (39-85) 8 Docetaxel n= (42-84) 13 Male, % Disease stage, % IIIb IV Performance status, % 0 1 CNS metastasis, % 7 6 Prior paclitaxel, % Current/former smoker, % PD-L1 expression, % 1% 5% 10% Not quantifiable 83% (225/272) of patients had quantifiable PD-L1 expression Spigel D et al. J Clin Oncol. 2015;33:(suppl; Abstract 8009)

15 CheckMate-017: OS (Primary Endpoint) Overall Survival (%) Median OS mo, (95% CI) Nivolumab n= Time (months) Number of patients at risk Nivolumab Docetaxel OS 1-yr OS: 24% 9.2 (7.3, 13.3) HR = 0.59 (95% CI: 0.44, 0.79), P= ) 1-yr OS: 42% Nivolumab Docetaxel Docetaxel n= (5.1, 7.3) 015 CI = confidence interval; HR = hazard ratio. Spigel D et al. J Clin Oncol. 2015;33:(suppl; Abstract 8009).

16 CheckMate-017: PFS (Per Investigator Assessment) 016 Spigel D et al. J Clin Oncol. 2015;33:(suppl; Abstract 8009).

17 CheckMate-017: OS and PFS by PD-L1 Expression 017 Survival benefit with nivolumab is independent of PD- L1 expression level Spigel D et al. J Clin Oncol. 2015;33:(suppl; Abstract 8009).

18 Phase 2 Trial of Atezolizumab vs Docetaxel in 2nd/3rd-line NSCLC (POPLAR) 018 Archival or fresh tissue required for pre-dose testing Spigel AI et al. J Clin Oncol. 2015;33:(suppl; Abstract 8010).

19 POPLAR: Baseline Characteristics 019 Characteristics of patients with NSCLC Atezolizumab (n=144) Docetaxel (n=143) Median age, yr % 39% Male 65% 53% Histology Non-squamous 66% 66% Squamous 34% 34% ECOG score, 0/1 33%/67% 32%/68% No. of prior chemotherapies, 1/2 65%/35% 67%/33% History of tobacco use Never 19% 20% Current 17% 15% Previous 64% 65% Spigel AI et al. J Clin Oncol. 2015;33:(suppl; Abstract 8010).

20 PD-L1 Expression on TC and IC Is a Potential Predictive Biomarker for Atezolizumab in NSCLC 020 Spigel AI et al. J Clin Oncol. 2015;33:(suppl; Abstract 8010).

21 POPLAR: OS (All Patients, ITT) 021 a Stratified HR; data cut-off Jan 30, Spigel AI et al. J Clin Oncol. 2015;33:(suppl; Abstract 8010).

22 POPLAR: PD-L1 Expression and OS 022 Spigel AI et al. J Clin Oncol. 2015;33:(suppl; Abstract 8010).

23 POPLAR: PD-L1 Expression and PFS 023 Spigel AI et al. J Clin Oncol. 2015;33:(suppl; Abstract 8010).

24 Pembrolizumab in the Treatment of NSCLC 024 Garon EB et al. N Engl J Med. 2015;372:

25 Biomarker Analysis 025 Anti-PD-L1 antibody clone 22C3 (Merck) and a prototype IHC assay used to determine PD-L1 status/expression in contemporaneous biopsy samples PD-L1 positivity was defined as membranous staining in 1% of cells (neoplastic and intercalated mononuclear inflammatory cells) Membranous PD-L1 expression 50% selected as the cutoff on the basis of ease of use and ROC (receiveroperating-characteristic) analysis PS = proportion score. Garon EB et al. N Engl J Med. 2015;372: Low High PS: <1% 1%-49% 50%

26 Pembrolizumab in NSCLC: PFS Per Proportional Scores (PS) 026 Garon EB et al. N Engl J Med. 2015;372:

27 Pembrolizumab in NSCLC: OS Per Proportional Scores (PS) 027 Garon EB et al. N Engl J Med. 2015;372:

28 028 Current Considerations With Immunotherapeutic Approaches in the Treatment of NSCLC

29 RECIST Criteria May Not Best Reflect Response Patterns to Immuno-Oncology Agents 029 Tumour Change From Baseline (%) Therapy start 0 Thresholds for response 25 or PD (RECIST) 50 Graphs for illustrative 75 purposes showing 100 responses to ipilimumab in advanced melanoma Time (days) Response after initial increase in tumour volume. Novel and specific to I-O therapy (RECIST or WHO criteria may not be appropriate to assess) Therapy start Tumour Change From Baseline (%) Response in baseline lesions: Typically seen with chemotherapy, but also I-O therapies. Captured by existing RECIST and WHO criteria SD : Slow, steady decline in tumour volume seen with chemotherapy, targeted, and I-O therapies. Captured by existing RECIST and WHO criteria 50 Therapy start Time (days) Time (days) I-O = Immuno-Oncology. Figures adapted from Wolchok JD et al. Clin Cancer Res. 2009;15: ; Hoos A et al. Ann of Oncol. 2012;23(suppl 8):viii47 viii52. Tumour Change From Baseline (%) Time (days) Reduction in tumour burden after appearance of new lesions. Novel and specific to I-O therapy (RECIST or WHO criteria may not be appropriate to assess) Therapy start Total Baseline New lesions 25 Tumour Change From Baseline (%)

30 Is Monotherapy Enough? 030 ORR ranges from 15% to 24.8% for anti-pd-1/pd-l1 monotherapy in previously treated or untreated patients with NSCLC Depends on your expectations!

31 What Is the Right Partner for Combination? 031 Chemotherapy? Atezolizumab + platinum doublet untreated NSCLC: ORR of 67% 1 Nivolumab + platinum doublet shows similar efficacy with nivolumab monotherapy in untreated NSCLC (CheckMate-012) 2 Another checkpoint inhibitor (eg, ipilimumab)? Nivolumab + ipi in 2nd-line NSCLC: 39% ORR 3 Targeted agent? Nivolumab + erlotinib in erlotinib failure patients: 19% ORR 4 Tolerability (discontinuation due to treatment-related AEs)? Nivolumab + platinum doublet: 21% 2 Nivolumab + erlotinib: 19% 4 1. Liu SV et al. J Clin Oncol. 2015;33:(suppl; Abstract 8030). 2. Antonia SJ et al. Multidisciplinary Symposium in Thoracic Oncology Abstract Patnaik A et al. J Clin Oncol. 2015;33:(suppl; Abstract 8011). 4. Rivni NA et al. J Clin Oncol. 2014:32:(suppl; Abstract 8022).

32 Anti-PD-1/PD-L1 in EGFR Mutation+ NSCLC? CheckMate Treatment effect on OS in predefined subgroups Paz-Ares et al. ASCO Abstract LBA109.

33 033 PD-L1 as a Potential Predictive Biomarker?

34 PD-L1 as a Potential Predictive Biomarker? 034 Kerr K. ASCO Discussant.

35 PD-L1 as a Potential Predictive Biomarker? (cont d) Spira et al. ASCO Abstract 8010 POPLAR: Atezolizumab vs docetaxel in prev-rx NSCLC PD-L1 as measured appears predictive of ORR, PFS and OS 035 Kerr K. ASCO Discussant.

36 PD-L1 as a Potential Predictive Biomarker? (cont d) PD-L1 expression on TC and IC is a potential predictive biomarker for atezolizumab in NSCLC 036 Kerr K. ASCO Discussant. TC scored as percentage of tumour cells positive - any intensity IC scored as percentage of tumour area with positive cells - any intensity TC3 or IC3 = TC 50% or IC 10% PD-L1+ TC2/3 or IC2/3 = TC or IC 5% PD-L1+ TC1/2/3 or IC1/2/3 = TC or IC 1% PD-L1+ TC0 and IC0 = TC and IC<1% PD-L1

37 OS and PFS Hazard Ratios by PD-L1 Status (CheckMate017) 037 PD-L1 expression NIVO Patients, n DOC Unstratified HR(95% Cl) OS 1% (0.45, 1.05) <1% (0.37, 0.92) All hazard ratios 5% (0.31, 0.89) <5% (0.47, 1.02) 10% Favour Nivolumab (0.28, 0.89) <10% over Docetaxel (0.48, 1.01) Not quantifiable at baseline (0.19, 0.82) PFS 1% Regardless 63 of (0.44, 1.01) <1% PD-L1 status (0.43, 1.00) 5% (0.32, 0.90) <5% (0.52, 1.08) in squamous cell 10% (0.33, 1.02) <10% carcinoma (0.49, 0.99) Not quantifiable at baseline (0.23, 0.89) Spigel D et al. J Clin Oncol. 2015;33:(suppl; Abstract 8009) NIVO DOC

38 OS and PFS Hazard Ratios by PD-L1 Status (CheckMate057) 038 PD-L1 expression level NIVO n DOC n Unstratified HR (95% Cl) OS HRs 1% (0.43, 0.82) <1% (0.66, 1.24) 5% Favour (0.30, 0.63) <5% Nivolumab (0.77, 1.34) 10% over (0.26, 0.59) <10% (0.76, 1.31) Docetaxel Not quantifiable at baseline (0.61, 1.35) PFS in 1% (0.53, 0.94) <1% PD-L (0.88, 1.61) 5% positive (0.39, 0.76) <5% (1.01, 1.71) 10% Nonsquamous (0.37, 0.75) <10% (0.96, 1.61) Not quantifiable at baseline (0.73, 1.56) cell carcinoma P-value a < NIVO DOC a Interaction P-value from Cox proportional hazard model with treatment, PD-L1 status and treatment by PD-L1 status interaction. Paz-Ares L et al. J Clin Oncol. 2015;33:(suppl; Abstract LBA109).

39 Differences Between Squamous and Non-Squamous Cancers? 039 Kerr K. ASCO Discussant. Biomarker not predictive in Squamous (017) but predictive in non-squamous (057) CheckMate057: Significant improvement in median OS but not median PFS CheckMate017: Significant improvement in median OS and PFS Same drug, same biomarker Current/former smokers CheckMate 017: 92% CheckMate 057: 79.5%; EGFR/ALK in 17.5% Greater mutational load in 017 squamous cell cancers? Immune system and squamous vs glandular epithelia? Does the immune status or immune microenvironment differ between these patients? Immune infiltrates in and around tumours differ Does the mutation burden make a difference? Are immunomodulatory mechanisms different? Are the cut offs correct? Are 1, 5 & 10% too low?

40 PD-L1 as a Potential Predictive Biomarker? (cont d) 040 Data are variable Rule in/rule out Biomarker to predict patient will benefit (and to what degree) Biomarker to predict patient will not benefit 10% is easier than 5% is easier than 1% Assessment of immune cells Relevance of immune cells present? Cytology samples lack architecture Is a biomarker required? Kerr K. ASCO Discussant.

41 PD-L1 as a Potential Predictive Biomarker? (cont d) 041 Is it the correct marker? Does the oncology community trust immunohistochemistry? Are our expectations of a biomarker in this setting reasonable? PD-L1 is not present or absent Expression is biological continuum Cut offs; definitions of positive are artificial Kerr K. ASCO Discussant.

42 PD-L1 as a Potential Predictive Biomarker? (cont d) 042 Is it the correct marker? Does the oncology community trust immunohistochemistry? Are our expectations of a biomarker in this setting reasonable? PD-L1 is not present or absent Expression is biological continuum Cut offs; definitions of positive are artificial Immune Checkpoint inhibition is NOT like inhibiting an addictive oncogene driver Four drugs, four different biomarker tests, all for PD-L1 Kerr K. ASCO Discussant.

43 Other Potential Biomarkers for Response? 043 Other immune checkpoints Immune cells Overall infiltrate Specific cell types Immune gene signatures Mutational burden Global burden Mismatch repair genes (MMR) Microsatellite instability (MSI) Polymerase E (POLE) mutations Smoking

44 044 Immune Checkpoint Inhibition Is an Active Area of Clinical Development in the Treatment of NSCLC

45 Phase 3 Trials With Immunotherapeutic Agents in NSCLC 045 Agent Patients Regimen 1 Endpoint Status Ipilimumab (NCT ) Ipilimumab (NCT ) Nivolumab (NCT ) Nivolumab (NCT ) Nivolumab (NCT ) Stage IV or recurrent SCC Chemo-naive or recurrent stage IV or recurrent NSCLC Stage IIIB-IV NSCLC; failed at least one prior systemic regimen Chemo-naive or recurrent stage IV NSCLC Chemo-naive or recurrent stage IV NSCLC Ipilimumab + CP vs Placebo + CP Nivolumab vs nivolumab + Ipi vs platinum doublet* Nivolumab 3 mg/kg IV until progression vs Nivolumab 3 mg/kg IV 1 year Nivolumab vs platinum doublet Nivo vs nivo + ipi vs platinumdoublet OS OS PFS Grade 3-4 and 5 treatment-related AEs PFS OS PFS Currently recruiting Not yet recruiting Currently recruiting Currently recruiting Not yet recruiting *Squamous: gemcitabine + cisplatin or carboplatin; non-squamous: pemetrexed + cisplatin or carboplatin. CP = carboplatin + paclitaxel. Available at: Accessed July 15, 2015.

46 Phase 3 Trials With Immunotherapeutic Agents in NSCLC 046 Agent Patients Regimen 1 Endpoint Status Pembrolizumab (NCT ) Untreated stage IV strong PD-L1- expressing NSCLC Pembro vs PC vs Pem + C vs Pem + Cis vs Gem + Cis vs Gem + C PFS Currently recruiting Pembrolizumab (NCT ) MEDI4736 (NCT ) Chemo-naive PD-L1+ NSCLC Chemo-naive advanced or metastatic NSCLC Pembro vs Standard of care platinum doublet MEDI vs MEDI + Treme vs platinum doublet OS PFS Currently recruiting Not yet recruiting MEDI4736 (NCT ) Stage IIIb/IV NSCLC failed 2 prior therapies PD-L1+: MEDI vs SOC PD-L1-: MEDI vs SOC vs MEDI + Treme vs SOC PFS Currently recruiting SOC = standard-of-care; C = carboplatin. Available at: Accessed July 15, 2015.

47 Phase 3 Trials With Immunotherapeutic Agents in NSCLC 047 Agent Patients Regimen 1 Endpoint Status MEDI4736 (NCT ) MEDI4736 (NCT ) MEDI4736 (NCT ) Completely resected NSCLC T790M+NSCLC failed prior EGFR TKI Stage III NSCLC not progressed following definitive platinum-based concurrent chemoradiation MEDI vs placebo DFS Currently recruiting MEDI + AZD9291 vs AZD9291 MEDI vs placebo PFS OS PFS Not yet recruiting Currently recruiting Available at: Accessed July 15, 2015.

48 Phase 3 Trials With Immunotherapeutic Agents in NSCLC 048 Agent Patients Regimen 1 Endpoint Status Atezolizumab (NCT ) Atezolizumab (NCT ) Atezolizumab (NCT ) Atezolizumab (NCT ) Atezolizumab (NCT ) Atezolizumab (NCT ) Chemo-naive, stage IV squamous NSCLC Chemo-naive or recurrent stage IV or recurrent NSCLC Chemo-naive or recurrent stage IV or recurrent NSCLC Chemo-naive stage IV SCC Chemo-naive stage IV NSCLC Completely resected stage IB- IIIA NSCLC MPDL vs Gem + Cis vs Gem + C MPDL vs C or cis + pem MPDL + nab-cp vs nab-cp MPDL + CP or MPDL + nab-cp vs nab-cp MPDL + CP vs MPDL + CP + bev vs CP + bev PFS PFS PFS PFS PFS Currently recruiting Currently recruiting Currently recruiting Currently recruiting Currently recruiting MPDL vs BSC DFS Currently recruiting CP = carboplatin + paclitaxel; nab-cp = carboplatin + nab-paclitaxel; C = carboplatin. Available at: Accessed July 15, 2015.

49 049 Vaccines in the Treatment of NSCLC

50 MOA of Cancer Vaccines 050 Tumour cells Adapted from Drakes CG et al. Nat Rev Clin Oncol. 2014;11:24-37.

51 MAGE-A3 and Adjuvant Therapy 051 MAGE-A3 is an antigen that is expressed almost exclusively on the surface of tumour cells, including NSCLC % of NSCLC expresses MAGE-A3 Expression is associated with poor prognosis Phase 2 trial in stage IB-II completely resected NSCLC: MAGE-A3 vaccine vs SOC 2 DFS: HR 0.76 (95% CI: ) OS: HR 0.81 (95% CI: ) MAGRIT trial: Phase 3 trial of MAGE-A3 cancer vaccines vs placebo in stage IB-IIIA completed resected NSCLC (N=2278) 3 2:1 randomisation Primary endpoint: DFS Study was discontinued by GSK due to failure to meet its primary endpoint 1. Massarelli E et al. Transl Lung Cancer Res. 2014;3:53-63; 2. Vansteenkiste J et al. J Clin Oncol. 2013;31: ; 3. GSK website. Accessed August 4, 2015.

52 Select Ongoing Phase 3 Trials With Vaccine in NSCLC 052 Agent Patients Regimen 1 Endpoint Status EGF cancer vaccine (NCT ) Untreated EGFR WT NSCLC EGF cancer vaccine vs BSC OS Currently recruiting Tergenpumatucel-L (NCT ) Progressive or relapsed NSCLC Tergenp vs docetaxel OS Currently recruiting GV1001 (NCT ) Inoperable stage III postchemoradiation therapy GV1001 vs BSC OS Not yet recruiting Racotumomab (NCT ) Previously treated stage IIIA-B, IV NSCLC Racotumomab vs BSC OS Currently recruiting TG4010 (NCT ) Untreated stage IV NSCLC TG chemo vs placebo + chemo PFS (Phase 2) OS (Phase 3) Currently recruiting BSC = best supportive care. Available at: Accessed July 15, 2015.

53 BI *: Therapeutic mrna-based Vaccine 053 A novel investigational therapeutic mrna-based vaccine developed in collaboration with CureVac Mobilises the patient s own immune system to fight the tumour with a specific immune response Clinical investigation is underway in lung cancer settings Source: *This is an investigational compound and has not yet been approved. Its safety and efficacy have not yet been fully established. mrna = messenger ribonucleic acid. Source: Boehringer Ingelheim (data on file).

54 BI : Current Clinical Development st -line EGFR m+ combo with afatinib Monotherapy in locally advanced disease after chemoradiation

55 Summary/Conclusion 055 Recent advances in molecular biology have revived and validated immunotherapeutic approaches for the treatment of cancer Anti-PD-L1mAb has significantly improved survival in patients with advanced or metastatic NSCLC However, there are still a number of issues associated with anti-pd-1/pd-l1 therapy, and it continues to be an active area of research and development Additional therapeutic approaches under clinical development include cancer vaccination