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 Brahmer8

1Fox Chase Cancer Center, Philadelphia, PA, USA; 2Memorial Sloan Kettering Cancer Center, New York, NY, USA; 3Hospital Universitario Doce de Octubre, CNIO, Universidad Complutense & CiberOnc, Madrid, Spain; 4Winship Cancer Institute,

Emory University, Atlanta, GA, USA; 5LungenClinic Grosshansdorf, German Center for Lung Research, Grosshansdorf, Germany;

6Princess Alexandra Hospital Brisbane, Queensland, Australia; 7Bristol-Myers Squibb, Princeton, NJ, USA; 8Sidney 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

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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 NSCLC1

– 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
• utcomes vs chemo in patients with non-squamous NSCLC2-5

– In patients with <1% PD-L1 expression, PFS HRs: 0.75 and 0.774,5

• 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. Abstract CT076. 3

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression

CheckMate 227 Part 1 Study Design

• Co-primary endpoints: OS in PD-L1–selected populations and PFSc in TMB-selected populations treated with nivolumab + ipilimumab

vs chemotherapy

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N = 1189 <1% PD-L1 expressionb N = 550

Nivolumab 3 mg/kg Q2W Ipilimumab 1 mg/kg Q6W n = 396 Histology-based chemotherapya n = 397 Nivolumab 240 mg Q2W n = 396 Nivolumab 3 mg/kg Q2W Ipilimumab 1 mg/kg Q6W n = 187 Histology-based chemotherapya n = 186 Nivolumab 360 mg Q3W + histology-based chemotherapya n = 177

Key eligibility criteria

• Stage IV or recurrent NSCLC
• No prior systemic therapy
• No known sensitizing

EGFR/ALK alterations

• ECOG PS 0–1

Stratified by SQ vs NSQ

R 1:1:1

Database lock: January 24, 2018; minimum follow-up: 11.2 months

aNSQ: 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; bOne patient was randomized with <1% tumor PD-L1 expression in IVRS, but was subsequently found to have ≥1% tumor PD-L1 expression; cPer BICR

Secondary endpoint: Nivolumab + chemotherapy vs chemotherapy

• PFSc in patients with <1% tumor

PD-L1 expression R 1:1:1

≥1% PD-L1 expression

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

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Nivolumab + chemotherapy (n = 177) Nivolumab + ipilimumab (n = 187) Chemotherapy (n = 186) Median age, y 64 63 64 Female, % 27 26 33 ECOG PS,a % 1 33 66 37 63 31 68 Smoking status, % Current/former smoker Never smoker Unknown 84 15 1 87 12 1 85 15 Histology, % Squamous Non-squamous 24 76 25 75 25 75 TMB, % Evaluable High (≥10 mut/Mb) Low (<10 mut/Mb) 55 44 56 48 42 58 58 45 55

aIn the chemo arm, ECOG PS for 1 patient was not reported; 1 patient in each arm was reported as ECOG PS ≥2

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

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Nivo + chemo (n = 177) Chemo (n = 186) Median PFS,a,b mo 5.6 4.7 HR (95% CI) 0.74 (0.58, 0.94)

a95% CI: nivo + chemo (4.6, 6.7 mo), chemo (4.3, 5.6 mo); bIn 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)

Nivolumab + chemotherapy Chemotherapy

• No. at risk

Nivo + chemo 177 134 72 48 31 13 2 Chemo 186 121 56 22 11 6 3

1-y PFS = 26% 1-y PFS = 14%

20 40 60 80 100 6 12 18 3 9 15 21 PFS (%) Months

All Randomized Patients (Squamous and Non-squamous)

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

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Nivo + chemo (n = 65) Chemo (n = 43) Median DOR,a mo 7.2 4.7

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

a95% CI: nivo + chemo (5.9, 9.4 mo), chemo (3.7, 5.8 mo)

ORR

10 20 30 40

Nivo + chemo Chemo

ORR (%)

65/177 n/N: 43/186

36.7 23.1 DOR

Patients in response (%) Months

65 57 35 18 7 5 1 43 28 10 6 3 Nivo + chemo Chemo

• No. at risk

100 80 60 40 20 3 6 9 12 15 18 21

Chemotherapy Nivolumab + chemotherapy ≥1-y DOR = 28% ≥1-y DOR = 24%

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

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Subgroup Nivo + chemo n Chemo 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 1 2 0 .5

Chemo Nivo + Chemo

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

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Subgroup Nivo + chemo n Chemo 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 1 2 0 .5

Chemo Nivo + Chemo

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression

PFS: Nivolumab + Chemotherapy vs Chemotherapy By TMB

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a95% CI: nivo + chemo (4.3, 9.1 mo), chemo (4.0, 6.8 mo); b95% CI: nivo + chemo (4.2, 6.9 mo), chemo (3.9, 6.2 mo)

• 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

Nivo + chemo 43 36 21 14 9 5 2

• No. at risk

48 30 16 4 1 1 1 Chemo Nivo + chemo (n = 43) Chemo (n = 48) Median PFS,a mo 6.2 5.3 HR (95% CI) 0.56 (0.35, 0.91) Nivolumab + chemotherapy

Months

Chemotherapy

TMB ≥10 mut/Mb and <1% Tumor PD-L1 Expression

1-y PFS = 27% 1-y PFS = 8%

Months TMB <10 mut/Mb and <1% Tumor PD-L1 Expression

Nivo + chemo (n = 54) Chemo (n = 59) Median PFS,b mo 4.7 4.7 HR (95% CI) 0.87 (0.57, 1.33)

20 40 60 80 100 6 12 18 3 9 15 21

Nivolumab + chemotherapy Chemotherapy 1-y PFS = 18% 1-y PFS = 16% 54 38 19 13 6 3 59 39 16 6 6 3 1 Nivo + chemo

• No. at risk

Chemo

PFS (%) 20 40 60 80 100 6 12 18 3 9 15 21

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

Exploratory analysis

a95% CI: nivo + chemo (4.3, 9.1 mo), nivo + ipi (2.7, NR mo), chemo (4.0, 6.8 mo)

Nivo + chemo (n = 43) Nivo + ipi (n = 38) Chemo (n = 48) Median PFS,a mo 6.2 7.7 5.3 HR (vs chemo) (95% CI) 0.56 (0.35, 0.91) 0.48 (0.27, 0.85) Nivo + chemo 43 36 21 14 9 5 2

• No. at risk

Nivolumab + chemotherapy Chemotherapy

48 30 16 4 1 1 1 Chemo

Nivolumab + ipilimumab

Months

1-y PFS = 45% 1-y PFS = 27% 1-y PFS = 8%

20 40 60 80 100 6 12 18 3 9 15 PFS (%) 21

Nivo + ipi 38 20 16 15 10 8 4 1

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CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression

Exploratory analysis

a95% CI: nivo + chemo (4.6, NR mo), nivo + ipi (12.2, NR mo), chemo (2.7, 6.9 mo)

Nivo + chemo (n = 26) Nivo + ipi (n = 14) Chemo (n = 10) Median DOR,a mo 7.4 NR 4.4

• ORR was 60.5% with nivo + chemo, 36.8% with nivo + ipi, and 20.8% with chemo

40 100 80 60 20

14 13 12 8 6 3 2 Nivo + ipi 26 22 15 8 3 3 1 Nivo + chemo 10 7 3 1 Chemo

Months

Nivolumab + ipilimumab Nivolumab + chemotherapy ≥1-y DOR = 33% ≥1-y DOR = 93% Chemotherapy ≥1-y DOR = NC

Patients in response (%) 3 6 9 12 15 18 21

• No. at risk

DOR: Nivolumab + Chemotherapy and Nivolumab + Ipilimumab in Patients With TMB ≥10 mut/Mb and <1% Tumor PD-L1 Expression

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CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression

PFS: Nivolumab + Chemotherapy and Nivolumab + Ipilimumab By TMB

13 Exploratory analysis

a95% CI: nivo + chemo (4.3, 9.1 mo), nivo + ipi (2.7, NR mo), chemo (4.0, 6.8 mo); b95% CI: nivo + chemo (4.2, 6.9 mo), nivo + ipi (1.6, 5.4 mo), chemo (3.9, 6.2 mo)

Nivolumab + chemotherapy Nivo + chemo (n = 54) Nivo + ipi (n = 52) Chemo (n = 59) Median PFS,b mo 4.7 3.1 4.7 HR (vs chemo) (95% CI) 0.87 (0.57, 1.33) 1.17 (0.76, 1.81) Nivolumab + ipilimumab 1-y PFS = 18% 1-y PFS = 18%

Months

Chemotherapy 1-y PFS = 16%

TMB <10 mut/Mb and <1% Tumor PD-L1 Expression TMB ≥10 mut/Mb and <1% Tumor PD-L1 Expression

Nivolumab + chemotherapy

Months

1-y PFS = 45% 1-y PFS = 27% Nivo + chemo (n = 43) Nivo + ipi (n = 38) Chemo (n = 48) Median PFS,a mo 6.2 7.7 5.3 HR (vs chemo) (95% CI) 0.56 (0.35, 0.91) 0.48 (0.27, 0.85)

Nivo + chemo

• No. at risk

Nivo + ipi 38 20 16 15 10 8 4 1 43 36 21 14 9 5 2 48 30 16 4 1 1 1 Chemo

20 40 60 80 100 6 12 18 3 9 15 21

Chemotherapy 1-y PFS = 8%

PFS (%)

• No. at risk

Nivo + ipi 52 22 12 7 5 3 1 59 39 16 6 6 3 1 Chemo Nivo + chemo 54 38 19 13 6 3

Nivolumab + ipilimumab

20 40 60 80 100 6 12 18 3 9 15 21

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression

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Nivolumab + chemotherapy (n = 172) Nivolumab + ipilimumab (n = 185) Chemotherapy (n = 183) Any grade Grade 3–4 Any grade Grade 3–4 Any grade Grade 3–4 Any TRAE,a % 92 52 74 25 77 35 TRAE leading to discontinuation,b % 13 8 16 10 14 9 Median number of doses received, n 8.5 for nivolumab (Q3W) 4–7 for chemo (Q3W) 8.0 for nivolumab (Q2W) 3.0 for ipilimumab (Q6W) 4–7 for chemo (Q3W)

Safety Summary of Treatment-Related AEs

aIncludes events reported between first dose and 30 days after last dose of study drug; bFor nivolumab + ipilimumab, these events include TRAEs leading to discontinuation of ipilimumab or

both study drugs (patients could not discontinue nivolumab without discontinuing ipilimumab); for nivolumab + chemo, patients who discontinued nivolumab or chemo or both were counted as having a TRAE leading to discontinuation; cNivolumab + ipilimumab arms, n = 576; dChemo arms, n = 570

• There were 4 treatment-related deaths in the nivolumab + chemo arm, 7 in both nivolumab + ipilimumab arms in Part 1,c and

6 in both chemo arms in Part 1d

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression

Most Frequent TRAEs (≥15%)

aSelect AEs are those with potential immunologic etiology that require frequent monitoring/intervention

• 1. Langer C, et al. Lancet Oncol 2016;17:1497–508. 2. Hellmann MD, et al. N Engl J Med 2018;378:2093–104.
• TRAEs in the chemo arm were consistent with prior reports1,2

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Anemia Nausea Fatigue Decreased appetite Constipation Neutropenia Decreased neutrophil count Skin Gastrointestinal Hepatic Endocrine

50% 50%

Select TRAEsa

Patients (%)

Nivo + chemo (n = 172) Nivo + ipi (n = 185)

40% 30% 20% 10% 10% 20% 30% 40%

Grade 1–2 Grade 3–4 Grade 1–2 Grade 3–4

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression

Summary: Nivolumab + Ipilimumab and Nivolumab + Chemotherapy in 1L NSCLC With <1% Tumor PD-L1 Expression

• Nivolumab + chemo vs chemo PFS HR was 0.74 (95% CI: 0.58, 0.94)a in patients with <1% PD-L1

expression,b consistent with other PD-(L)1 + chemo studies

• TMB testing may be clinically relevant to select patients for IO + chemo in addition to IO + IO

– In patients with <1% PD-L1 expression, PFS benefit from nivolumab + chemo vs chemo was enhanced with high TMB (≥10 mut/Mb) – Patients with low TMB (<10 mut/Mb) and <1% PD-L1 did not appear to have PFS benefit from nivolumab in combination with either chemo or ipilimumab

• Responses were more durable and 1-year PFS rates were higher with nivolumab + ipilimumab vs

nivolumab + chemo in patients with high TMB (≥10 mut/Mb) and <1% PD-L1 expression

• There were fewer grade 3–4 TRAEs with nivolumab + ipilimumab than nivolumab + chemo

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aNSQ PFS HR = 0.68 (95% CI: 0.51, 0.90); bNSQ and SQ

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression

CheckMate 227 Part 1 Investigators

17 Greece: H. Linardou, P. Makrantonakis,

• D. Mavroudis, K. Syrigos

Hungary: I. Albert, G. Losonczy, G. Ostoros Ireland: O. Breathnach, L. Coate, S. Cuffe,

• P. Donnellan

Israel: J. Bar, A. Cyjon, M. Gottfried, H. Nechushtan,

• S. Stemmer

Italy: A. Ardizzoni, R. Bartolucci, L. Bonomi,

• F. Cappuzzo, R. Chiari, F. Cognetti, F. De Marinis,
• M. Garassino, C. Gridelli, E. Minenza

Japan: K. Azuma, H. Daga, Y. Fujisaka, T. Fukuhara,

• K. Goto, M. Harada, A. Hata, T. Hida, K. Hotta, S. Ikeda,
• A. Inoue, Y. Iwamoto, K. Kasahara, I. Kinoshita,
• K. Kubota, T. Kurata, K. Minato, T. Naito, M. Nishio,
• N. Nogami, Y. Ohe, H. Okamoto, I. Okamoto, T. Okano,
• H. Saka, H. Sakai, M. Satouchi, S. Sugawara,
• M. Takeda, Y. Takiguchi, H. Tanaka, N. Yamamoto,
• T. Yokoyama

Lebanon: M. Ghosn, A. Tfayli Mexico: J. Alatorre Alexander, F. Bustamante Valles,

• S. Campos Gomez, E. De la Mora Jimenez,
• P. Gonzalez, O. Hernandez Flores,
• F. Medina-Soto, M. Perez Martinez, J. Reyes Contreras,
• M. Segura Gonzalez, L. Vazquez Cortes

Netherlands: J. Aerts, S. Burgers, R. Cornelissen,

• AJ. De Langen, M. Youssef-El Soud

Peru: F. Hurtado De Mendoza, L. Mas, C. Vallejos Argentina: S. Bella, C. Brocca, M. Flores,

• E. Korbenfeld, R. Kowalyszyn, L. Lupinacci, C. Martin,
• E. Richardet, MS. Varela, J. Zarba

Australia: M. Chan, K. Feeney, M. George,

• R. Joshi, A. Khattak, D. Leong, B. Markman,

S-A. McLachlan, A. Nagrial, K. O’Byrne Austria: T. Fuereder, R. Kolb, H. Stoeger Belgium: B. Colinet, I. Demedts, K. Deschepper,

• V. Surmont, J. Van Meerbeeck

Brazil: L. Araujo, C. Barrios, G. De Castro, F. Franke,

• C. Haddad, P. Marchi, C. Mathias, T. Oliveira

Canada: J-S. Aucoin, V. Cohen, F. Couture, R. Lester,

• K. Marquis, S. Martel, M. Pavic, R. Sangha, M. Vincent

Chile: O. Aren Frontera, P. Gonzalez Mella, P. Salman Colombia: R. Bruges, A. Cardona Zorrilla, A. Quiroga,

• G. Rojas

Czech Republic: L. Havel, V. Kolek Finland: J. Koivunen, T. Saariaho France: C. Audigier-Valette, F. Barlesi, C. Chouaid,

• R. Corre, P. Fournel, R. Gervais, M. Ginoux,
• B. Mennecier, J. Raimbourg, L. Thiberville, R. Veillon,
• A. Vergnenegre, V. Westeel, G. Zalcman

Germany: H. Bischoff, P. Fix, N. Frickhofen, W. Gleiber,

• C. Grohé, M. Kimmich, K. Kokowski, S. Lang, M. Reck,
• J. Schreiber, M. Schuler, C. Schumann, W. Schütte,
• M. Serke

Poland: E. Kalinka-Warzocha, K. Lesniewski-Kmak,

• I. Pawlak, A. Pluzanski, R. Suwinski,
• J. Wojcik-Tomaszewska, B. Zurawski

Republic of Korea: J-H. Kang, S-W. Kim, JS. Lee,

• KH. Lee, K. Park

Romania: A. Alexandru, T. Ciuleanu, M. Schenker,

• A. Ungureanu

Russian Federation: O. Gladkov, N. Karaseva,

• K. Laktionov, A. Luft, V. Moiseyenko,
• G. Mukhametshina, D. Sakaeva

South Africa: S. Chan, L. Dreosti, B. Rapoport, D. Rens Spain: R. Bernabe Caro, A. Blasco,

• E. Carcereny Costa, A. Martinez Marti, L. Paz-Ares,
• S. Ponce, M. Provencio

Switzerland: M. Mark, A. Mueller, S. Peters,

• S. Rothschild

Taiwan: G-C. Chang, C-H. Chiu, K-Y. Lee, C-T. Yang, C-J. Yu United Kingdom: S. Ahmed, D. Chao, D. Gilligan, L. Li,

• M. Mackean, G. Middleton, C. Ottensmeier, S. Popat,
• J. Spicer

United States: W. Akerley, S. Arledge, F. Badin,

• B. Bolemon, H. Borghaei, J. Brahmer, H. Chen,
• A. Dowlati, E. Gamboa, D. Gerber, S. Gettinger,
• M. Hellmann, L. Horn, A. Kramer, P. Lowry,
• D. Morgensztern, S. Nair, G. Otterson, R. Oyola,
• S. Ramalingam, R. Reilly, R. Siegel, J. Wrangle,
• R. Zinner

CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression

Acknowledgments

• The patients and families who made this trial possible
• The clinical study teams who participated in the trial
• The protocol managers for this study, Suresh Alaparthy, Judith Bushong, and Christopher Coira

(Bristol-Myers Squibb)

• Haolan Lu (Bristol-Myers Squibb) for contributions to the statistical analysis plan
• Han Chang, Joseph Szustakowski, and William Geese (Bristol-Myers Squibb) for contributions to

the biomarker analyses

• Foundation Medicine for collaborative development of the FoundationOne CDx™ assay
• Dako for collaborative development of the PD-L1 IHC 28-8 pharmDx assay
• Bristol-Myers Squibb (Princeton, NJ) and ONO Pharmaceutical Company Ltd. (Osaka, Japan)
• All authors contributed to and approved the presentation; writing and editorial assistance was

provided by Dawn L. Lee, PhD, of Evidence Scientific Solutions Inc, funded by Bristol-Myers Squibb

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CheckMate 227: Nivo + Ipi, Nivo + Chemo, and Chemo in 1L NSCLC With <1% Tumor PD-L1 Expression

Abbreviations

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1L = first-line AE = adverse event BICR = blinded independent central review CI = confidence interval DOR = duration of response ECOG PS = Eastern Cooperative Oncology Group performance status HR = hazard ratio Ipi = ipilimumab IO = immuno-oncology IVRS = Interactive Voice Response System Mb = Megabase Mut = mutation NC = not calculable Nivo = nivolumab NR = not reached NSCLC = non-small cell lung cancer NSQ = non-squamous ORR = objective response rate OS = overall survival PD-L1 = programmed death ligand 1 PFS = progression-free survival Q2W = every 2 weeks Q3W = every 3 weeks Q6W = every 6 weeks R = randomized SQ = squamous TMB = tumor mutational burden TRAE = treatment-related adverse event