Phase I/II CheckMate 032: Nivolumab ± Ipilimumab in Advanced SCLC CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois *Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

Nivolumab ± Ipilimumab in Advanced SCLC (CheckMate 032): Background Few treatment options, poor prognosis for pts with recurrent SCLC CheckMate 032: phase I/II trial evaluating nivolumab with or without ipilimumab in multiple tumor types including SCLC that progressed after platinum-based treatment Early data from nonrandomized pt cohort suggested durable responses and promising survival in SCLC Nivolumab ± ipilimumab included in guidelines for SCLC Current report presents first results from randomized cohort added to further evaluate nivolumab ± ipilimumab in SCLC SCLC, small-cell lung cancer. Slide credit: clinicaloptions.com Hellmann MD, et al. ASCO 2017. Abstract 8503. Antonia SJ, et al. Lancet Oncol. 2016;17:883-895.

CheckMate 032: Study Design Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg IV Q3W x 4 cycles Nivolumab 3 mg/kg IV Q2W Pts with SCLC that progressed after ≥1 prior platinum-based therapy Nivolumab 3 mg/kg IV Q2W Until PD or unacceptable toxicity PD, progressive disease; RECIST, Response Evaluation Criteria in Solid Tumors; SCLC, small-cell lung cancer. Primary objective: ORR per RECIST v1.1 Same dosing regimens used for randomized (3:2) and nonrandomized cohorts Slide credit: clinicaloptions.com Hellmann MD, et al. ASCO 2017. Abstract 8503.

Nivolumab + ipilimumab CheckMate 032: Response Outcomes for Nonrandomized Cohort With Extended Follow-up Response Characteristic Nivolumab (n = 98) Nivolumab + ipilimumab (n = 61) ORR, % PD-L1 ≥ 1% PD-L1 < 1% 11 9 14 23 10 32 Median time to response, mos (range) 1.4 (1.1-4.1) 2.0 (1.0-4.1) Median duration of response, mos (range) 17.9 (2.8-34.6+) 14.2 (1.5-26.5+) Ongoing responses at 2 yrs, % 45 36 Slide credit: clinicaloptions.com Hellmann MD, et al. ASCO 2017. Abstract 8503.

CheckMate 032: OS for Nonrandomized Cohort With Extended Follow-up 100 Median OS, Mos (95% CI) 4.1 (3.0-6.8) 7.8 (3.6-14.2) Minimum Follow-up, Mos 19.6 20.2 90 80 Nivolumab Nivolumab + ipilimumab 70 60 OS (%) 50 1-yr OS: 40% 40 30 2-yr OS: 26% 1-yr OS: 27% 20 10 2-yr OS: 14% 3 6 9 12 15 18 21 24 27 30 33 36 39 Pts at Risk, n Nivolumab Nivolumab + ipilimumab Mos 98 61 56 43 39 33 35 28 26 24 21 21 17 19 12 16 7 14 7 7 6 3 4 1 4 1 0 0 Slide credit: clinicaloptions.com Hellmann MD, et al. ASCO 2017. Abstract 8503. Reproduced with permission.

CheckMate 032: Pt Characteristics (Randomized Cohort) Nivolumab (n = 147) Nivolumab + Ipilimumab (n = 95) Mean age (SD), yrs ≥ 65 yrs, % 63 (29-83) 44 65 (41-91) 51 Male, % 59 63 Prior treatment regimens, % 1 2-3 67 33 Platinum sensitive, % 50 42 Current or former smoker, % 92 95 ECOG PS 0 /1, % 33 / 67 28 / 71 ECOG, Eastern Cooperative Oncology Group; PS, performance status; SD, standard deviation. Slide credit: clinicaloptions.com Hellmann MD, et al. ASCO 2017. Abstract 8503.

CheckMate 032: Efficacy in Randomized and Nonrandomized Pt Cohorts Outcome Randomized Cohort Nonrandomized Cohort Nivolumab (n = 147) Nivolumab + Ipilimumab (n = 95) (n = 98) (n = 61) ORR, % 12 21 11 23 TTR, mos 1.5 1.4 2.0 3-mo PFS, % 18 30 27 36 3-mo OS, % 65 64 59 72 TTR, time to response. Responses observed regardless of number of prior lines of therapy, platinum sensitivity or resistance Slide credit: clinicaloptions.com Hellmann MD, et al. ASCO 2017. Abstract 8503.

CheckMate 032: Safety (Pooled Cohorts) Treatment-Related AE, % Nivolumab (n = 245) Nivolumab + Ipilimumab (n = 156) Any Grade 3/4 55 12 73 37 Skin 16 <1 36 6 Endocrine 8 21 3 Hepatic 2 Gastrointestinal 5 24 Pulmonary 4 Leading to discontinuation 13 10 Resolution of Gr 3/4 NA 45 78 AE, adverse event; NA, not applicable. 4 treatment-related deaths in combination arm (myasthenia gravis, pneumonitis, seizures/encephalitis, autoimmune hepatitis) vs 1 in nivolumab arm (pneumonitis) Slide credit: clinicaloptions.com Hellmann MD, et al. ASCO 2017. Abstract 8503.

CheckMate 032: Conclusions Response durability and survival promising with nivolumab ± ipilimumab in extended follow-up of nonrandomized cohort of pts with advanced SCLC Efficacy of nivolumab ± ipilimumab in randomized cohort of pts with advanced SCLC consistent with prior nonrandomized cohort Higher incidence of grade 3/4 treatment-related AEs and deaths with combination therapy Randomized phase III trials ongoing in SCLC Nivolumab ± ipilimumab as maintenance therapy after initial chemotherapy (CheckMate 451) Nivolumab alone vs chemotherapy as second line therapy (CheckMate 331) AE, adverse event; SCLC, small-cell lung cancer. Slide credit: clinicaloptions.com Hellmann MD, et al. ASCO 2017. Abstract 8503.

Go Online for More CCO Coverage of ASCO 2017! Short slideset summaries and additional CME-certified analyses with expert faculty commentary on key studies in: Breast cancer Gastrointestinal cancer Genitourinary cancer Gynecologic cancers Hematologic malignancies Lung cancer Skin cancer clinicaloptions.com/oncology