1. May 29 - June 2, 2015 KEYNOTE-028: Antitumor Activity With Pembrolizumab in Patients With PD-L1- Positive Extensive-Stage SCLC 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, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

2. clinicaloptions.com/oncology KEYNOTE-028: Early Efficacy, Safety With Pembrolizumab in Patients With SCLC Small-Cell Lung Cancer  Small-cell lung cancer: ~ 15% of all lung cancers [1]  Associated with poor outcomes –Median OS: ≤ 12 mos –5-yr OS: ≤ 3%  Current recommended treatments [2] –First line: 4-6 cycles of cisplatin (or carboplatin) + etoposide  cranial irradiation (prophylactic) –Second line: topotecan (single agent) –Associated with 15% to 20% ORR and 30% 1-yr OS –No improvement seen with other regimens 1. National Cancer Institute PDQ. Small cell lung cancer. 2. NCCN. Guidelines: small cell lung cancer. v.2.2015.

3. clinicaloptions.com/oncology KEYNOTE-028: Early Efficacy, Safety With Pembrolizumab in Patients With SCLC Pembrolizumab  High-affinity monoclonal antibody against PD-1 –PD-1, inhibitory receptor on tumor cell that, when bound to ligands PD-L1 and PD-L2, blocks T-cell antitumor activity  Pembrolizumab blocks interaction between PD-1 and ligands –Active in multiple tumor types Ott PA, et al. ASCO 2015. Abstract 7502.

4. clinicaloptions.com/oncology KEYNOTE-028: Early Efficacy, Safety With Pembrolizumab in Patients With SCLC Earlier Studies With Pembrolizumab in Thoracic Cancers  Current study sought to evaluate safety and preliminary efficacy of pembrolizumab in pts with PD-L1–positive advanced solid tumor SCLC [3] Pembrolizumab in Thoracic Cancers StudyPopulationOutcomes KEYNOTE-001 [1] Treatment-naive and treatment- experienced pts with NSCLC (N = 495)  All pts -ORR: 19.4% -Median OS: 12.0 mos  Pts with high PD-L1 -ORR: 45.2% -Median OS: Not reached KEYNOTE-028 [2] Pts with malignant pleural mesothelioma (n = 25) ORR: 28% DCR: 76% 1. Garon EB, et al. N Engl J Med. 2015;372:2018-2028. 2. Alley EA, et al. AACR 2015. Abstract CT104. 3. Ott PA, et al. ASCO 2015. Abstract 7502.

5. clinicaloptions.com/oncology KEYNOTE-028: Early Efficacy, Safety With Pembrolizumab in Patients With SCLC 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.

6. clinicaloptions.com/oncology KEYNOTE-028: Early Efficacy, Safety With Pembrolizumab in Patients With SCLC KEYNOTE-028: Baseline Characteristics (SCLC Cohort) Pt Characteristics (n = 20) Male sex, n (%)11 (55) Median age, yrs (range)69.5 (41-71) Race, n (%)  White  Asian  Other/not specified 12 (60) 3 (15) 5 (25) ECOG PS, n (%)  0  1 5 (25) 15 (75) Stable brain metastases, n (%)2 (10) Histology, n (%)  Small cell  Neuroendocrine 19 (95) 1 (5) Previous Therapies, n (%)  Chemotherapy  Radiotherapy  Investigational 20 (100) 1 (5) 2 (10)  Cisplatin/carboplatin + etoposide  Irinotecan or topotecan  Taxane 20 (100) 9 (45) 7 (35) Ott PA, et al. ASCO 2015. Abstract 7502.

7. clinicaloptions.com/oncology KEYNOTE-028: Early Efficacy, Safety With Pembrolizumab in Patients With SCLC 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, %

8. clinicaloptions.com/oncology KEYNOTE-028: Early Efficacy, Safety With Pembrolizumab in Patients With SCLC KEYNOTE-028: Safety in SCLC  Small numbers of pts with toxicity grade ≥ 3 –Median follow-up: 21 wks (range: 2-48 wks)  Toxicity mainly as previously seen with pembrolizumab  Treatment-related discontinuations: n = 2 –Autoimmune thyroiditis, colitis  Treatment-related death: n = 1 (colitis)  No cases of pneumonitis Pembrolizumab Toxicity (n = 20), n (%) Any toxicity  Grade 3-5 14 (70) 2 (10) Arthralgia3 (15) Asthenia  Grade 3-5 3 (15) 1 (5) Grade 2 autoimmune thyroiditis 1 (5) Nausea2 (10) Rash2 (10) Grade 3-5 bilirubin increases 1 (5) Grade 5 colitis1 (5) Ott PA, et al. ASCO 2015. Abstract 7502.

9. clinicaloptions.com/oncology KEYNOTE-028: Early Efficacy, Safety With Pembrolizumab in Patients With SCLC KEYNOTE-028: Investigator Conclusions  Pembrolizumab shows promising antitumor activity in treatment-experienced pts with PD-L1–positive SCLC  Safety and efficacy similar with pembrolizumab in other tumor types  Other phase I and II trials ongoing in pts with extensive- stage SCLC

10. Go Online for More CCO Coverage of ASCO 2015! clinicaloptions.com/oncology Short slidesets of all the key data Additional CME-certified analyses with expert faculty commentary on all the key studies in:  Gastrointestinal cancers  Genitourinary cancer  Hematologic malignancies  Immunotherapy  Lung cancer