1. May 29 – June 2, 2015 Lung Cancer CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting* *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. This program is supported by educational grants from AstraZeneca, Bayer, Celgene Corporation, Genentech, Incyte and Novartis. Jointly provided by the Annenberg Center for Health Sciences at Eisenhower and Clinical Care Options, LLC

2. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies CheckMate 017: Nivolumab vs Docetaxel in Previously Treated Squamous NSCLC  Open-label, randomized phase III trial  Primary endpoint: OS  Secondary endpoints: ORR, PFS, efficacy by PD-L1 expression, safety, QoL Spigel DR, et al. ASCO 2015. Abstract 8009. Brahmer J, et al. N Engl J Med. 2015;373:123-135. Pts with stage IIIB/IV squamous NSCLC and ECOG PS 0-1 with failure of 1 previous platinum doublet chemotherapy (N = 272) Nivolumab 3 mg/kg IV q2w (n = 135) Docetaxel 75 mg/m 2 IV q3w (n = 137) Until disease progression or unacceptable toxicity Stratified by previous paclitaxel therapy (yes vs no) and region

3. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies CheckMate 017: OS in the ITT Population Spigel DR, et al. ASCO 2015. Abstract 8009. Brahmer J, et al. N Engl J Med. 2015;373:123-135. 100 90 80 70 60 50 40 30 20 10 0 Overall Survival (% of Patients) 03691215182124 Mos At Risk, n Nivolumab Docetaxel 135 137 113 103 86 68 69 45 52 30 31 14 15 7 72720 Nivolumab (N = 135) Docetaxel (N = 137) HR for death, 0.59 (0.44-0.79) P <.001 Nivolumab Docetaxel Median OS mo (95% CI) 9.2 (7.3-13.3) 6.0 (5.1-7.3) 1-Yr OS % of patients (95% CI) 42 (34-50) 24 (17-31) No. of Deaths 86 113

4. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies CheckMate 017: OS by PD-L1 Expression  OS benefit seen with nivolumab vs docetaxel independent of PD-L1 expression; similar trend in PFS, ORR Median OS by PD-L1 Expression Level,* Mos NivolumabDocetaxelUnstratified HR (95% CI) Interaction P Value ≥ 1% < 1% 9.3 8.7 7.2 5.9 0.69 (0.45-1.05) 0.58 (0.37-0.92).56 ≥ 5% < 5% 10.0 8.5 6.4 6.1 0.53 (0.31-0.89) 0.70 (0.47-1.02).47 ≥ 10% < 10% 11.0 8.2 7.1 6.1 0.50 (0.28-0.89) 0.70 (0.48-1.01).41 Not quantifiable0.39 (0.19-0.82) Spigel DR, et al. ASCO 2015. Abstract 8009. Brahmer J, et al. N Engl J Med. 2015;373:123-135. * PD-L1 expression measured in pre-treatment tumor biopsies with validated, automated immunohistochemical assay using PD-L1 antibody clone 28–8.

5. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies CheckMate 057: Nivo vs Docetaxel in Previously Treated Nonsquamous NSCLC  Primary endpoint: OS  Secondary endpoints: ORR, PFS, efficacy by PD-L1 expression, safety, QoL Pts with stage IIIB/IV nonsquamous NSCLC and ECOG PS 0-1 who failed 1 prior platinum doublet chemotherapy ± TKI therapy (N = 582) Nivolumab 3 mg/kg IV q2w (n = 292) Docetaxel 75 mg/m 2 IV q3w (n = 290) Paz-Ares L, et al. ASCO 2015. Abstract LBA109. Until disease progression or unacceptable toxicity Stratified by previous maintenance therapy (yes vs no) and line of therapy (second vs third line)

6. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies CheckMate 057: OS in the ITT Population Paz-Ares L, et al. ASCO 2015. Abstract LBA109. Reprinted with permission. 100 90 80 70 60 50 40 30 20 10 0 Overall Survival (%) 03691215182127 Time (Mos) At Risk, n Nivolumab Docetaxel 292 290 232 244194 169 150 146 111 123 88 32 10 95950 mOS, mo 1-yr OS rate = 51% Nivolumab Docetaxel Nivolumab (n = 292) 12.2 24 1-yr OS rate = 39% Docetaxel (n = 290) 9.4 HR = 0.73 (96% CI: 0.59, 0.89); P =.0015 62 34

7. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies CheckMate 057: OS by PD-L1 Expression  Similar interaction results based on baseline PD-L1 expression observed for PFS and ORR Median OS by PD-L1 Expression Level, mos NivolumabDocetaxelUnstratified HR (95% CI) Interaction P Value ≥ 1% < 1% 17.2 10.4 9.0 10.1 0.59 (0.43-0.82) 0.90 (0.66-1.24).0646 ≥ 5% < 5% 18.2 9.7 8.1 10.1 0.43 (0.30-0.63) 1.01 (0.77-1.34).0004 ≥ 10% < 10% 19.4 9.9 8.0 10.3 0.40 (0.26-0.59) 1.00 (0.76-1.31).0002 Paz-Ares L, et al. ASCO 2015. Abstract LBA109. Reprinted with permission.

8. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies POPLAR: Atezolizumab vs Docetaxel in Previously Treated NSCLC  Primary endpoint: OS in PD-L1–selected and ITT populations  Secondary endpoints: overall safety as well as PFS, ORR, DoR in PD- L1–selected and ITT populations Pts with locally advanced or metastatic NSCLC and ECOG PS 0-1 who failed prior platinum-containing chemotherapy (N = 287) Atezolizumab 1200 mg IV q3w (n = 144) Docetaxel 75 mg/m 2 IV q3w (n = 143) Stratified by PD-L1 immune cell expression (0 vs 1 vs 2 vs 3), histology (squamous vs nonsquamous), and line of therapy (second vs third line) Spira AI, et al. ASCO 2015. Abstract 8010.

9. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies POPLAR: Efficacy of Atezolizumab According to PD-L1 Expression  PFS and ORR: similar trends in outcome for atezolizumab vs docetaxel based on PD-L1 expression ‒ Median PFS in ITT population: 2.8 vs 3.4 mos (HR: 0.98) ‒ Median PFS in TC3 or IC3 population: 7.8 vs 3.9 mos (HR: 0.57) ‒ ORR in ITT population: 15% vs 15% ‒ ORR in TC3 or IC3 population: 38% vs 13%  Interim data based on minimum of 10 mos of follow-up Interim Median OS Outcomes Atezolizumab (n = 144) Docetaxel (n = 143) HR (95% CI)P Value ITT population (N = 287)11.49.50.77 (0.55-1.06).11 Subgroups based on PD-L1 expression*  TC0 and IC0 (n = 92)  TC1/2/3 or IC1/2/3 (n = 195)  TC2/3 or IC2/3 (n = 105)  TC3 or IC3 (n = 47) 9.7 NR 13.0 NR 9.7 9.1 7.4 11.1 1.12 (0.64-1.93) 0.63 (0.42-0.94) 0.56 (0.33-0.94) 0.46 (0.19-1.09).70.024.026.070 Spira AI, et al. ASCO 2015. Abstract 8010. *PD-L1 expression measured by SP142 IHC assay (low expression – TC0/IC0, high expression - TC3/IC3).

10. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies POPLAR: Safety Profile  AEs: consistent with prior studies –Incidence of individual immune-related AEs ≤ 4% for atezolizumab  AEs (all grades) occurring with ≥ 5% difference between arms ‒ Increased incidence in atezolizumab arm: decreased appetite, dyspnea, arthralgia, insomnia, musculoskeletal pain, pneumonia, hypothyroidism ‒ Increased incidence in docetaxel arm: alopecia, nausea, diarrhea, anemia, asthenia, myalgia, neutropenia, peripheral neuropathy, febrile neutropenia, peripheral sensory neuropathy Spira AI, et al. ASCO 2015. Abstract 8010. Safety Outcome Atezolizumab (n = 142) Docetaxel (n = 135) Median treatment duration, mos3.72.1 Treatment-related AEs, %6788 Treatment-related grade 3/4 AEs, %1239 All-cause grade 5 AEs, %44 Treatment discontinuation due to AEs, %822

11. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies KEYNOTE-021 Advanced NSCLC Cohort: Ipilimumab + Pembrolizumab  Standard 3 + 3 dose escalation [1] –Ipi (0.3, 1, or 3 mg/kg) + Pembro (2 or 10 mg/kg) q3w –Protocol amended during study to treat all subsequent pts with Ipi 1 mg/kg + Pembro 2 mg/kg q3w based on toxicity concern [2]  Primary endpoint: DLTs in first 3 weeks  Secondary endpoints: safety and tolerability, ORR 1. Patnaik A, et al. ASCO 2015. Abstract 8011. Reprinted with permission. 2. Antonia SJ, et al. ASCO 2014. Abstract 8023. Previously treated advanced/metastatic NSCLC including ≥ 1 platinum doublet CT, ECOG PS 0/1 0 3 6 9 12 15 18 21 24 27 30 33 36 /// 105 Pembrolizumab up to 2 yrs Ipilimumab 4 doses Wk

12. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies KEYNOTE-021 NSCLC Cohort: Tumor Response  ORR (N = 18): 39% including 1 CR Patnaik A, et al. ASCO 2015. Abstract 8011. Reprinted with permission. -120 -100 -80 -60 -40 -20 0 20 40 60 80 100 Change From Baseline, % 71% of patients showed decrease in target lesion burden Pembrolizumab 10mg/kg + ipilimumab 1 or 3 mg/kg Pembrolizumab 2mg/kg + ipilimumab 1mg/kg

13. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies Durvalumab + Tremelimumab Dual Checkpoint Blockade in NSCLC Antonia SJ et al. ASCO 2015. Abstract 3014. Reprinted with permission. 100 50 0 -50 -100 Change From Baseline (%) 56081624324048 Time (Wks) D10 Q4W/T1 D20 Q4W/T1 By Dose Cohort D15 Q4W/T1 D10 Q2W/T1 By PD-L1 Status 100 50 0 -50 -100 Best Change From Baseline (%) PD-L1+ PD-L1- PD-L1 na

14. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies PD-L1 as a Biomarker in Lung Cancer Atezolizumab [1] Nivolumab [2] Pembrolizumab [3] Anti-PD-L1 IHC Ab SP14228-822C3 Tumor tissue Fresh/Archival Target cell staining TC or ICTC Scoring thresholds, cells 0: < 1% (TC/IC) 1: ≥ 1% - < 5% (TC/IC) 2: ≥ 5% - < 50% (TC); ≥ 5% - < 10% (IC) 3: ≥ 50% (TC); ≥ 10% (IC) ≥ 1% ≥ 5% ≥ 10% ≥ 25% ≥ 50% PS < 1% (low) PS 1% – 49% (intermediate) PS ≥ 50% (high) 1. Horn L, et al. ASCO 2015. Abstract 8029. 2. Gettinger SN, et al. ASCO 2015. Abstract 8025. 3. Rizvi NA, et al. ASCO 2015. Abstract 8026. Increased PD-L1 expression correlated with increased efficacy outcomes

15. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies KEYNOTE-028: Pembrolizumab in Advanced SCLC  Multicohort, open-label phase Ib trial  Primary Endpoint: ORR (per RECIST v. 1.1), safety  Secondary Endpoints: PFS, OS, duration of response  PD-L1 expression assessed by centrally reviewed IHC (22C3 antibody) SCLC Cohort Pts with PD-L1– positive SCLC and failure or inability to receive standard therapy; ECOG PS 0-1; ≥ 1 measurable lesion; no autoimmune disease or interstitial lung disease (n = 20) Pembrolizumab 10 mg/kg IV q2w for 24 mos or until progression or intolerable toxicity Pembrolizumab 10 mg/kg IV q2w Discontinue treatment CR, PR, or SD Progressive disease or unacceptable toxicity Ott PA, et al. ASCO 2015. Abstract 7502.

16. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies KEYNOTE-028: Tumor Response  Pembrolizumab therapy associated with partial response in 7 pts –5/7 responders with tumor reduction > 50% in size –6/7 responders with reduction in tumor size by Wk 8 Outcomes Responsen% (95% CI) ORR  CR  PR 0707 0 35 (15-59) Stable disease15 (0-25) Progressive disease 945 (23-69) No assessment315 (3-38) Ott PA, et al. ASCO 2015. Abstract 7502. Reprinted with Permission. Change From Baseline in Tumor Size (RECIST v1.1, Investigator Review) 100 80 60 40 20 0 -20 -40 -60 -80 -100 Change From Baseline, %

17. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies CheckMate 032: Nivolumab ± Ipilimumab in Previously Treated SCLC Nivolumab 3 mg/kg IV q2w (n = 40) Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg IV q3w (n = 47) Nivolumab 1 mg/kg + Ipilimumab 1 mg/kg IV q3w (n = 3) Pts with recurrent SCLC + prior platinum-based treatment (N = 128) Antonia SJ, et al. ASCO 2015. Abstract 7503. Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg IV q3w (n = 38) Nivolumab 3 mg/kg IV q2w Analyzed separately 4 cycles Endpoints  Primary: ORR  Secondary: safety  Exploratory: PFS, OS, biomarker analysis

18. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies Response Nivolumab (n = 40) Nivolumab + Ipilimumab (n = 46) ORR, % 1817* CR, % 02.2 PR, % 1815 SD, % 2037 PD, % 5337 Median time to response, mo 1.62.2 Median DoR, mos (range) NR (4.1 to > 11)6.9 (1.5 to > 11.1) Median OS, mos 4.48.2 CheckMate 032: Efficacy Outcomes Antonia SJ, et al. ASCO 2015. Abstract 7503. *7 additional PRs after database lock increased ORR to 32.6% in combination arm.

19. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies Safety Outcome, % Nivolumab (n = 40) Nivolumab + Ipilimumab (n = 50) Treatment-related deaths 02.1 Treatment-related discontinuation 7.511 Any GradeGrade 3/4Any GradeGrade 3/4 Treatment-related AE 53157734 CheckMate 032: Safety  Safety profiles of both treatments consistent with other tumor types –Paraneoplastic syndromes and autoimmune diseases require close monitoring Antonia SJ, et al. ASCO 2015. Abstract 7503.

20. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies AURA: AZD9291 in Previously Untreated Advanced NSCLC Predefined expansion cohorts Sequential cohorts of pt with previously untreated LA/ metastatic NSCLC with confirmed EGFR mutation, WHO PS 0-1 Cohort 5 (240 mg) T790M+ Cohort 4 (160 mg) (n = 30) T790M+/- Cohort 3 (80 mg) (n = 30) T790M+/- Cohort 2 (40 mg) T790M+/- Cohort 1 (20 mg) T790M+ Ramalingam SS, et al. ASCO 2015. Abstract 8000. AZD9291 Dosing

21. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies -70 -50 -30 -10 AURA: Tumor Response and PFS Outcome 80 mg (n = 30) 160 mg (n = 30) Total (N = 60) Maximum DoR, mos13.8*9.7* PFS, % (95% CI)  3 mos  6 mos  9 mos  12 mos 90 (72-97) 83 (64-93) 73 (51-87) 97 (79-100) 90 (72-97) 78 (57-89) NC 93 (83-97) 87 (75-93) 81 (68-89) 72 (55-64) Ramalingam SS, et al. ASCO 2015. Abstract 8000. Reprinted with permission. *Ongoing. 50 40 30 20 10 0 -20 -40 -60 -80 -90 -100 80 mg 160 mg Best Percentage Change From Baseline in Target Lesion Individual Patients D D D D D D D D D D D *

22. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies AURA: Safety  Most common toxicities: skin rash, diarrhea, dry skin, stomatitis; mostly grade 1  No grade ≥ 3 hyperglycemia, QT prolongation, or ILD-like events AE, % 80 mg (n = 30) 160 mg (n = 30) Total (N = 60) Any event grade ≥ 3 334338 Treatment-related AE 9710098 Treatment-related AE grade ≥ 3 102015 Treatment-related AE leading to discontinuation 735 Treatment-related serious AE 1037 Ramalingam SS, et al. ASCO 2015. Abstract 8000.

23. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies TIGER-X: Rociletinib in Previously Treated EGFR Mutation-Positive NSCLC Rociletinib 500 mg BID (n = 119) EGFR mutation– positive previously treated advanced or recurrent NSCLC with acquired resistance to prior EGFR TKI (N = 456) Key outcomes: safety and tolerability, PK profile, ORR Sequist LV, et al. ASCO 2015. Abstract 8001. Rociletinib 625 mg BID (n = 236) Rociletinib 750 mg BID (n = 95) Phase II expansion cohorts  Upon progression on EGFR TKI  T790M+ biopsy at entry  Stable CNS metastases ok Phase I dose escalation Rociletinib BID 21-day cycles escalate to MTD

24. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies TIGER-X: Tumor Response Across Rociletinib Dosing Sequist LV, et al. ASCO 2015. Abstract 8001. Reprinted with permission. 100 80 60 40 20 0 -20 -40 -60 -80 -100 SLD Change From Baseline (%) 500 mg BID HBr 625 mg BID HBr 750 mg BID HBr 1000 mg BID HBr Ongoing 500 mg625 mg750 mg1000 mgTotal N48114774243 ORR (%)6054467553 DCR (%)90848210085 Individual Patients

25. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies TIGER-X: Safety Across Rociletinib Dosing  Improved safety profile with 500 mg BID vs higher doses –Grade 3 QTc prolongation 2.5% –Discontinuation due to treatment-related AEs 2.5% vs 4% overall  Once recognized, hyperglycemia manageable with oral agents AE (All Grades), % 500 mg (n = 119) 625 mg (n = 236) 750 mg (n = 95) 1000 mg (n = 6) Hyperglycemia  Grade 3/4 35 17 45 24 59 36 67 33 Diarrhea 33403067 Nausea 19343750 QTc prolongation 13232650 Sequist LV, et al. ASCO 2015. Abstract 8001.

26. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies Dabrafenib + Trametinib in Previously Treated NSCLC With a BRAF Mutation  BRF113928: Single-arm, multicenter, open-label phase II trial  Interim analysis with N = 33 (safety population) –24 pts evaluated for efficacy  Primary endpoint: ORR (by investigator); secondary endpoints: PFS, OS, DoR, safety, tolerability, PK Dabrafenib 150 mg BID + Trametinib 2 mg QD (n = 20) Pts with progressing stage IV BRAF V600E–mutant NSCLC after 1-3 prior regimens (≥ 1 platinum-based) ECOG PS 0-2 (N = 40) Planchard D, et al. ASCO 2015. Abstract 8006. Dabrafenib 150 mg BID + Trametinib 2 mg QD (n = 20) If ≥ 6 responses Stage 1 Stage 2

27. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies BRF113928: Responses With Dabrafenib + Trametinib  Median time on study treament (dabrafenib and trametinib) = 108 days (range, 1 to 244 days) Planchard D, et al. ASCO 2015. Abstract 8006. Reprinted with permission. Individual Patients 0123456789 Treatment Duration (Mos) *1st-line patient (protocol deviation) Best Confirmed Response Partial Response Stable Disease Progressive Disease Not Evaluable Not Available First Partial Response Disease Progressed Still on Study Treatment

28. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies BRF113928: Safety With Dabrafenib + Trametinib  Most common AEs: pyrexia, diarrhea, nausea, vomiting, decreased appetite, asthenia, cough, peripheral edema, rash  1 death due to pleural effusion and disease progression Planchard D, et al. ASCO 2015. Abstract 8006. AE, % All Treated (n = 33) Any AE 88 Any grade ≥ 3 AE 45 Any serious AEs  Pyrexia  Confusional state  Hyponatremia 42 18 6 AE leading to discontinuation 6

29. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies MAPS: Randomized Trial of Cis/Pem ± Bev in Unresectable Mesothelioma  Open-label, multicenter, randomized phase II/III trial [1]  Primary endpoints –Phase II: disease-control rate at 6 mos; endpoint reached in January 2010 [2] –Phase III: OS [1] Pts with MPM; no CV comorbidity; PS 0-2; no previous chemotherapy; eligible for bevacizumab therapy (N = 448) Bevacizumab 15 mg/kg Day 1 q21d until progression Pemetrexed 500 mg/m² Day 1 + Cisplatin 75 mg/m² Day 1 + Bevacizumab 15 mg/kg Day 1 (n = 223) Pemetrexed 500 mg/m² Day 1 + Cisplatin 75 mg/m² Day 1 (n = 225) Surveillance* Stratified by center; epithelioid vs sarcomatoid or mixed histology; PS (0-1 vs 2); smoking status 1. Zalcman G, et al. ASCO 2015. Abstract 7500. 2. Zalcman G, et al. ASCO 2010. Abstract 7020. 6 cycles q21d *No crossover allowed

30. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies MAPS: PFS in the ITT Population  IDMC requested early release of data due to efficacy of experimental arm Zalcman G, et al. ASCO 2015. Abstract 7500. Reproduced with permission. Median PFS C/P + Bev: 9.6 mos (95% CI: 8.5-10.6) C/P: 7.5 mos (95% CI: 6.8-8.1) HR = 0.61 (95% CI: 0.50-0.75) P <.0001 1 0.9 0.8 0.7 0.6 0.5 0.3 0.2 0 0.4 0.1 0102030405060 Mos Progression-Free Survival Probability

31. clinicaloptions.com/oncology Lung Cancer and Other Thoracic Malignancies MAPS: Safety  Statistically significant increase in grade 3/4 drug toxicity in experimental arm –Statistically significant increase in grade 3/4 anemia in control arm Grade 3/4 Adverse Effect, n (%) Cisplatin/Pemetrexed + Bevacizumab (n = 222) Cisplatin/ Pemetrexed (n = 224) P Value Any grade 3/4 toxicity158 (71)139 (62).04 Any hematologic toxicity105 (47)111 (50).63 Neutropenia Febrile neutropenia 98 (44) 4 (2) 100 (45) 7 (3)*.91.37 Thrombocytopenia22 (10)9 (4).85 Anemia16 (7)30 (13).03 Zalcman G, et al. ASCO 2015. Abstract 7500. *Includes 1 death (grade 5) from febrile neutropenia in control arm.