Nivolumab + Ipilimumab, Nivolumab + Chemotherapy, and Chemotherapy - PowerPoint PPT Presentation

Nivolumab + Ipilimumab, Nivolumab + Chemotherapy, and Chemotherapy in Chemo-Naive Patients With Advanced Non-Small Cell Lung Cancer and <1% Tumor PD-L1 Expression: Results From CheckMate 227 Hossein Borghaei, 1 Matthew D. Hellmann, 2 Luis Paz-Ares, 3 Suresh S. Ramalingam, 4 Martin Reck, 5 Kenneth J. O’Byrne, 6 Prabhu Bhagavatheeswaran, 7 Faith Nathan, 7 Julie Brahmer 8 1 Fox Chase Cancer Center, Philadelphia, PA, USA; 2 Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3 Hospital Universitario Doce de Octubre, CNIO, Universidad Complutense & CiberOnc, Madrid, Spain; 4 Winship Cancer Institute, Emory University, Atlanta, GA, USA; 5 LungenClinic Grosshansdorf, German Center for Lung Research, Grosshansdorf, Germany; 6 Princess Alexandra Hospital Brisbane, Queensland, Australia; 7 Bristol-Myers Squibb, Princeton, NJ, USA; 8 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA 2018 ASCO Annual Meeting, June 1–5, Chicago, IL

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression Conflicts of Interest • Research Support (Clinical Trials): – Millennium, Merck/Celgene, BMS/Lilly • Advisory Board/Consultant: – BMS, Lilly, Genentech, Celgene, Pfizer, Merck, EMD-Serono, Boerhinger-Ingelheim, Astra Zeneca, Novartis, Genmab, Regeneron, BioNTech, Cantargia AB • DSMB: – University of Pennsylvania, CAR T Program • Employment: – Fox Chase Cancer Center 2

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression Introduction • CheckMate 227 is a phase 3 multi-part study investigating 1L nivolumab-based therapy vs chemo in advanced NSCLC 1 – The trial met its co-primary endpoint of improved PFS with nivolumab + ipilimumab in patients with TMB ≥10 mut/Mb – Benefit was durable and observed independent of PD-L1 expression levels and histology • Recent studies demonstrated the addition of anti-PD-(L)1 therapy to chemo can improve outcomes vs chemo in patients with non-squamous NSCLC 2-5 – In patients with <1% PD-L1 expression, PFS HRs: 0.75 and 0.77 4,5 • Here, we investigated the efficacy and safety of nivolumab + ipilimumab and nivolumab + chemo vs chemo in patients with <1% PD-L1 expression 1. Hellmann MD, et al. N Engl J Med 2018;378:2093–104. 2. Langer C, et al. Lancet Oncol 2016;17:1497–508. 3. Juergens RJ, et al. Presented at WCLC 2017 Annual Meeting; October 15–18, 2017; Yokohama, Japan. Abstract OA17.03. 4. Gandhi L, et al. N Engl J Med 2018;378:2078–92. 5. Kowanetz M, et al. Presented at AACR 2018 Annual Meeting; April 14–18, 2018; Chicago, IL. 3 Abstract CT076.

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression CheckMate 227 Part 1 Study Design Nivolumab 3 mg/kg Q2W Ipilimumab 1 mg/kg Q6W N = 1189 n = 396 R ≥1% PD-L1 Histology-based chemotherapy a expression n = 397 1:1:1 Nivolumab 240 mg Q2W Key eligibility criteria n = 396 • Stage IV or recurrent NSCLC • No prior systemic therapy • No known sensitizing EGFR / ALK alterations • ECOG PS 0–1 Nivolumab 3 mg/kg Q2W Ipilimumab 1 mg/kg Q6W Stratified by SQ vs NSQ N = 550 n = 187 R <1% PD-L1 Histology-based chemotherapy a Secondary endpoint: Nivolumab + expression b 1:1:1 n = 186 chemotherapy vs chemotherapy PFS c in patients with <1% tumor Nivolumab 360 mg Q3W + • histology-based chemotherapy a PD-L1 expression n = 177 Co-primary endpoints: OS in PD-L1–selected populations and PFS c in TMB-selected populations treated with nivolumab + ipilimumab • vs chemotherapy Database lock: January 24, 2018; minimum follow-up: 11.2 months a NSQ: pemetrexed + cisplatin or carboplatin, Q3W for ≤4 cycles, with optional pemetrexed maintenance following chemotherapy or nivolumab + pemetrexed maintenance following nivolumab + chemotherapy; SQ: gemcitabine + cisplatin, or gemcitabine + carboplatin, Q3W for ≤4 cycles; b One patient was randomized with <1% tumor PD-L1 expression in IVRS, but was subsequently found to have ≥1% tumor PD-L1 expression; c Per BICR 4

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression Baseline Characteristics in Patients With <1% Tumor PD-L1 Expression Nivolumab + Nivolumab + chemotherapy ipilimumab Chemotherapy (n = 177) (n = 187) (n = 186) Median age, y 64 63 64 Female, % 27 26 33 ECOG PS, a % 0 33 37 31 1 66 63 68 Smoking status, % Current/former smoker 84 87 85 Never smoker 15 12 15 Unknown 1 1 0 Histology, % Squamous 24 25 25 Non-squamous 76 75 75 TMB, % Evaluable 55 48 58 High (≥10 mut/Mb) 44 42 45 Low (<10 mut/Mb) 56 58 55 a In the chemo arm, ECOG PS for 1 patient was not reported; 1 patient in each arm was reported as ECOG PS ≥2 5

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression PFS: Nivolumab + Chemotherapy vs Chemotherapy in Patients With <1% Tumor PD-L1 Expression All Randomized Patients (Squamous and Non-squamous) 100 Nivo + chemo Chemo (n = 177) (n = 186) Median PFS, a,b mo 5.6 4.7 80 HR 0.74 (95% CI) (0.58, 0.94) 60 PFS (%) 40 1-y PFS = 26% 20 Nivolumab + chemotherapy 1-y PFS = 14% Chemotherapy 0 0 3 6 9 12 15 18 21 Months No. at risk 177 72 13 Nivo + chemo 134 48 31 2 0 Chemo 186 56 6 121 22 11 3 0 a 95% CI: nivo + chemo (4.6, 6.7 mo), chemo (4.3, 5.6 mo); b In the nivo + ipi arm (n = 187), median (95% CI) PFS was 4.4 (3.1, 6.0), 1-y PFS was 29%, and HR vs chemo was 0.79 (0.62, 1.01) 6

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression ORR and DOR in Patients With <1% Tumor PD-L1 Expression ORR DOR 100 Nivo + chemo Chemo 40 (n = 65) (n = 43) 36.7 Median DOR, a mo 7.2 4.7 Patients in response (%) 80 30 60 23.1 ORR (%) 20 ≥1-y DOR = 28% 40 ≥1-y DOR = 24% Nivolumab + chemotherapy 20 10 Chemotherapy 0 0 3 6 9 12 15 18 21 0 Months Nivo + chemo Chemo No. at risk n/N: 65/177 43/186 Nivo + chemo 65 57 35 18 7 5 1 0 Chemo 43 28 10 6 3 0 0 0 DOR per BICR; ORR was 25.1% (n/N: 47/187), median DOR was 18.0 mo (95% CI: 12.2, NR), and ≥1-y DOR was 72% in the nivo + ipi arm a 95% CI: nivo + chemo (5.9, 9.4 mo), chemo (3.7, 5.8 mo) 7

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression PFS Subgroup Analyses in Patients With <1% Tumor PD-L1 Expression Nivo + chemo Chemo Subgroup n n Unstratified HR Unstratified HR (95% CI) Overall 177 186 0.71 <65 years 91 98 0.59 ≥65 years 86 88 0.85 Male 130 125 0.70 Female 47 61 0.70 North America 25 15 0.65 Europe 90 92 0.59 Asia 36 43 0.72 Rest of world 26 36 1.12 ECOG PS 0 59 57 0.88 ECOG PS 1 117 127 0.64 Squamous 43 46 0.92 Non-squamous 134 140 0.68 TMB high (≥10 mut/Mb) 43 48 0.56 TMB low (<10 mut/Mb) 54 59 0.87 0 .2 5 0 .5 1 2 Chemo Nivo + Chemo 8

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression PFS Subgroup Analyses in Patients With <1% Tumor PD-L1 Expression Nivo + chemo Chemo Subgroup n n Unstratified HR Unstratified HR (95% CI) Overall 177 186 0.71 <65 years 91 98 0.59 ≥65 years 86 88 0.85 Male 130 125 0.70 Female 47 61 0.70 North America 25 15 0.65 Europe 90 92 0.59 Asia 36 43 0.72 Rest of world 26 36 1.12 ECOG PS 0 59 57 0.88 ECOG PS 1 117 127 0.64 Squamous 43 46 0.92 Non-squamous 134 140 0.68 TMB high (≥10 mut/Mb) 43 48 0.56 TMB low (<10 mut/Mb) 54 59 0.87 0 .2 5 0 .5 1 2 Chemo Nivo + Chemo 9

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression PFS: Nivolumab + Chemotherapy vs Chemotherapy By TMB TMB <10 mut/Mb and <1% Tumor PD-L1 Expression TMB ≥10 mut/Mb and <1% Tumor PD-L1 Expression Nivo + chemo Chemo Nivo + chemo Chemo (n = 43) (n = 48) (n = 54) (n = 59) 100 100 Median PFS, a mo Median PFS, b mo 6.2 5.3 4.7 4.7 HR 0.56 HR 0.87 80 80 (95% CI) (0.35, 0.91) (95% CI) (0.57, 1.33) PFS (%) 60 60 40 40 1-y PFS = 27% 1-y PFS = 18% Nivolumab + Nivolumab + 1-y PFS = 16% 20 chemotherapy 20 chemotherapy 1-y PFS = 8% Chemotherapy Chemotherapy 0 0 0 3 6 9 12 15 18 21 0 3 6 9 12 15 18 21 Months Months No. at risk No. at risk Nivo + chemo 43 36 21 14 9 5 2 0 Nivo + chemo 54 38 19 13 6 3 0 0 Chemo 4 1 0 48 30 16 1 1 Chemo 59 39 16 6 6 3 1 0 • TMB ≥10 mut/Mb: ORR was 60.5% with nivo + chemo and 20.8% with chemo • TMB <10 mut/Mb: ORR was 27.8% with nivo + chemo and 22.0% with chemo a 95% CI: nivo + chemo (4.3, 9.1 mo), chemo (4.0, 6.8 mo); b 95% CI: nivo + chemo (4.2, 6.9 mo), chemo (3.9, 6.2 mo) 10

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression PFS: Nivolumab + Chemotherapy and Nivolumab + Ipilimumab in Patients With TMB ≥10 mut/Mb and <1% Tumor PD-L1 Expression Nivo + chemo Nivo + ipi Chemo 100 (n = 43) (n = 38) (n = 48) Median PFS, a mo 6.2 7.7 5.3 80 HR (vs chemo) 0.56 0.48 (95% CI) (0.35, 0.91) (0.27, 0.85) 60 PFS (%) 1-y PFS = 45% Nivolumab + 40 ipilimumab 1-y PFS = 27% Nivolumab + 20 chemotherapy Chemotherapy 1-y PFS = 8% 0 0 3 6 9 12 15 18 21 Months No. at risk Nivo + chemo 43 36 21 14 9 5 2 0 Nivo + ipi 38 20 16 15 10 8 4 1 Chemo 48 30 16 4 1 1 1 0 Exploratory analysis a 95% CI: nivo + chemo (4.3, 9.1 mo), nivo + ipi (2.7, NR mo), chemo (4.0, 6.8 mo) 10