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Nivolumab (NIVO) + low-dose ipilimumab (IPI) vs platinum-doublet chemotherapy (chemo) as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (NSCLC): CheckMate 227 Part 1 final analysis

Date

28 Sep 2019

Session

Presidential Symposium I

Presenters

Solange Peters

Citation

Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Authors

S. Peters1, S.S. Ramalingam2, L. Paz-Ares3, R. Bernabe Caro4, B. Zurawski5, S. Kim6, A. Alexandru7, L. Lupinacci8, E. de la Mora Jimenez9, H. Sakai10, I. Albert11, A. Vergnenegre12, M. Reck13, H. Borghaei14, J.R. Brahmer15, K.J. O'Byrne16, W.J. Geese17, P. Bhagavatheeswaran17, F.E. Nathan18, M.D. Hellmann19

Author affiliations

  • 1 Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois - CHUV, Lausanne University, 1011 - Lausanne/CH
  • 2 Department Of Hematology And Medical Oncology, Winship Cancer Institute, Emory University, 30322 - Atlanta/US
  • 3 Medical Oncology Department, University Hospital 12 De Octubre and Universidad Complutense & CiberOnc, 28041 - Madrid/ES
  • 4 Medical Oncology Department, Hospital Universitario Virgen Del Rocio, Seville/ES
  • 5 Chemotherapy Department, Ambulatorium Chemioterapii, Bydgoszcz/PL
  • 6 Medical Oncology Department, Asan Medical Center, Seoul/KR
  • 7 Medical Oncology Department, Institute Of Oncology "Prof. Dr. Alexandru Trestioreanu" Bucha, Bucharest/RO
  • 8 Clinical Oncology Department, Hospital Italiano De Buenos Aires, C1181ACH - Buenos Aires/AR
  • 9 Medical Oncology Department, Instituto Jalisciense De Cancerología, Jalisco/MX
  • 10 Thoracic Oncology Department, Saitama Cancer Center, 362-0806 - Saitama/JP
  • 11 Pulmonary Department, Matrai Gyogyintezet, 3233 - Matrahaza/HU
  • 12 Medical Oncology Department, Limoges University Hospital, 87042 - Limoges/FR
  • 13 Department Of Thoracic Oncology And Clinical Trial Department, Lung Clinic Grosshansdorf, German Center for Lung Research, 22927 - Grosshansdorf/DE
  • 14 Hematology And Oncology Department, Fox Chase Cancer Center, Philadelphia/US
  • 15 Oncology Department, Sidney Kimmel Comprehensive Cancer Center At Johns Hopkins, 21287 - Baltimore/US
  • 16 Medical Oncology, Princess Alexandra Hospital, Brisbane, 4102 - Woolloongabba/AU
  • 17 Global Biometric Sciences, Bristol-Myers Squibb, Princeton/US
  • 18 Oncology Clinical Development, Bristol-Myers Squibb, 08540 - Princeton/US
  • 19 Department Of Medicine, Memorial Sloan-Kettering, 10017 - New York/US
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Background

Part 1 of CheckMate 227 (NCT02477826), a phase III study in 1L NSCLC, has dual primary endpoints. The primary endpoint of progression-free survival (PFS) with NIVO + IPI vs chemo in patients (pts) with tumor mutational burden ≥ 10 mut/Mb was met, as reported previously. Here we present the primary endpoint of overall survival (OS) for NIVO + IPI vs chemo in pts with tumor PD-L1 expression ≥ 1%.

Methods

Pts were chemo-naive, with stage IV or recurrent NSCLC without EGFR or known ALK alterations, ECOG PS 0–1. Pts with PD-L1 ≥1% (n = 1189) were randomized 1:1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 240 mg Q2W, or histology-based chemo; pts with PD-L1 < 1% (n = 550) were randomized 1:1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 360 mg Q3W + chemo, or chemo. Pts were stratified by histology in both populations. Pts were treated until disease progression, unacceptable toxicity, or for 2 y of immunotherapy.

Results

Baseline characteristics were balanced across tx arms. Minimum follow-up for the primary endpoint was 29.3 mo. For pts with PD-L1 ≥ 1%, OS was significantly longer with NIVO + IPI vs chemo (HR 0.79, 97.72% CI: 0.65–0.96; P = 0.007); PFS, objective response rates, and duration of response favored NIVO + IPI vs chemo. OS benefit was also observed in pts with PD-L1 < 1% and all randomized pts (Table). Prespecified analyses showed enhanced efficacy with NIVO + IPI relative to NIVO in PD-L1 ≥ 1% and relative to NIVO + chemo in PD-L1 < 1%. Grade 3–4 tx-related adverse event rates in all randomized pts were 33% with NIVO + low-dose IPI, 19% with NIVO, and 36% with chemo.Table: LBA4_PR

Efficacy outcomes with NIVO + IPI, NIVO, NIVO + chemo, and chemo in 1L advanced NSCLC with PD-L1 ≥ 1%, PD-L1 < 1%, and in all randomized pts in CheckMate 227 part 1

PD-L1 ≥ 1%NIVO + IPI n = 396Chemo n = 397NIVOa n = 396
Median OS, mo (95% CI) HR vs chemo (97.72% CI) P value 1-year OS rate, % 2-year OS rate, %17.1 (15.0–20.1) 0.79 (0.65–0.96) P = 0.007 63 4014.9 (12.7–16.7) - - 56 3315.7 (13.3–18.1) 0.88 (0.75–1.04)b - 57 36
Median PFS, mo (95% CI) HR vs chemo (95% CI)5.1 (4.1–6.3) 0.82 (0.69–0.97)5.6 (4.6–5.8) -4.2 (3.0–5.3) 0.99 (0.84–1.17)
Objective response rate, n (%) Median duration of response, mo (95% CI)142 (35.9) 23.2 (15.2–32.2)119 (30.0) 6.2 (5.6–7.4)109 (27.5) 15.5 (12.7–23.5)
PD-L1 < 1%NIVO + IPI n = 187Chemo n = 186NIVO + chemoc n = 177
Median OS, mo (95% CI) HR vs chemo (95% CI) 1-year OS rate, % 2-year OS rate, %17.2 (12.8–22.0) 0.62 (0.48–0.78) 60 4012.2 (9.2–14.3) - 51 2315.2 (12.3–19.8) 0.78 (0.62–0.98) 59 35
All randomized ptsNIVO + IPI n = 583Chemo n = 583
Median OS, mo (95% CI) HR vs chemo (95% CI) 1-year OS rate, % 2-year OS rate, %17.1 (15.2–19.9) 0.73 (0.64–0.84) 62 4013.9 (12.2–15.1) - 54 30
a

Study treatment only in PD-L1 ≥ 1% population;

b

95% CI for NIVO vs chemo;

c

study treatment only in PD-L1 < 1% population. Minimum follow-up for OS and PFS was 29.3 mo and for objective response rate, 28.3 mo.

Conclusions

CheckMate 227 met its primary endpoint of significantly improved OS with NIVO + IPI vs chemo in 1L advanced NSCLC with PD-L1 ≥ 1%. OS was also improved with NIVO + IPI in PD-L1 < 1% and in all randomized pts. Safety profile was consistent with previous reports in NSCLC. NIVO + IPI represents a new chemo-free tx option for pts in 1L advanced NSCLC.

Clinical trial identification

NCT02477826; Release date: June 23, 2015.

Editorial acknowledgement

Writing and editorial assistance was provided by Namiko Abe, PhD, of Caudex, funded by Bristol-Myers Squibb.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb.

Disclosure

S. Peters: Advisory / Consultancy, Research grant / Funding (institution): AbbVie, Amgen, AstraZeneca, Bayer, Biocartis, Bioinvent, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp and Dohme, M. S.S. Ramalingam: Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Personal fees, advisory board: Amgen; Honoraria (self), Advisory / Consultancy, Personal fees, advisory board: AbbVie; Honoraria (self), Advisory / Consultancy, Personal fees, advisory board: Lilly; Honoraria (self), Advisory / Consultancy, Personal fees, advisory board: Genentech; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Personal fees, advisory board: Takeda; Honoraria (self), Personal fees: Loxo; Research grant / Funding (institution): Advaxis; Honoraria (self), Research grant / Funding (institution), Personal fees: Tesaro; Honoraria (self), Research grant / Funding (institution), Personal fees: Merck; Honoraria (self), Research grant / Funding (self), Personal fees: AstraZeneca. L. Paz-Ares: Advisory / Consultancy, Advisory board: Genómica; Honoraria (self), Personal fees: Lilly, MSD, Roche, Pharmamar, Merck, AstraZeneca, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex, Amgen, Incyte, Pfizer, Ipsen, Adacap, Sanofi, Bayer, Blueprint, Bristol-Myers Squibb; Advisory / Consultancy, Scientific advice/speaker: Lilly, MSD, Roche, Pharmamar, Merck, AstraZeneca, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex, Amgen, Incyte, Pfizer, Ipsen, Adacap, Sanofi, Bayer, Blueprint, Bristol-Myers Squibb; Officer / Board of Directors, Co-founder and board member: Altum Sequencing; Research grant / Funding (institution), Grant: MSD, AstraZeneca, Pfizer, Bristol-Myers Squibb. H. Sakai: Research grant / Funding (institution), Grant: Ono Pharmaceutical Company, Bristol-Myers Squibb Company, AstraZeneca, Chugai Pharmaceutical Company, Merck & Co, Merck KGaA; Honoraria (self), Personal fees: Ono Pharmaceutical Company, Bristol-Myers Squibb Company, AstraZeneca, Chugai Pharmaceutical Company, Merck & Co, Merck KGaA. A. Vergnenegre: Honoraria (self), Advisory / Consultancy, Personal fees, travels for medical conferences and fees for consulting: Bristol-Myers Squibb, MSD, AstraZeneca. M. Reck: Honoraria (self), Advisory / Consultancy, Honoraria for lectures and consultancy: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche. H. Borghaei: Research grant / Funding (institution): Millennium, Merck/Celgene, Bristol-Myers Squibb/Lilly; Advisory / Consultancy: BMS, Lilly, Genentech, Celgene, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Cantargia AB, Amgen, AbbVie, Axiom, PharmaMar, Takeda, Huya Bio, Diiachi; Advisory / Consultancy, Data Safety and Monitoring Board: University of Pennsylvania, CAR T Program; Takeda; Full / Part-time employment: Fox Chase Cancer Center. J.R. Brahmer: Advisory / Consultancy, Research grant / Funding (institution), Grant, advisory board: Bristol-Myers Squibb; Advisory / Consultancy, Advisory board: AstraZeneca, Genentech, Merck. K.J. O’Byrne: Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory board and speaker bureau fees and travel grants to national and international meetings: Bristol-Myers Squibb, Pfizer, AstraZeneca, MSD, Roche-Genentech, Boehringer Ingelheim; Advisory / Consultancy, Advisory board: Novartis, Teva, Natera; Advisory / Consultancy, Speaker Bureau / Expert testimony, Advisory board and speaker bureau fees: Janssen-Cilag; Speaker Bureau / Expert testimony, Speaker bureau: Mundipharma; Shareholder / Stockholder / Stock options, Shareholder: Carp Pharmaceuticals, Carpe Vitae Pharmaceuticals; Licensing / Royalties, Various patents issues with licensee as listed: Queensland University of Technology and Trinity College Dublin. W.J. Geese: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. P. Bhagavatheeswaran: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. F.E. Nathan: Full / Part-time employment: Bristol-Myers Squibb. M.D. Hellmann: Advisory / Consultancy, Fees for consulting: Genentech, Merck, Novartis, Janssen, Mirati, Syndax, Nektar, Blueprint Medicines; Advisory / Consultancy, Research grant / Funding (institution), Research grant to institution, fees for consulting and travel (grant, personal fees, non-financial support): Bristol-Myers Squibb; Advisory / Consultancy, Fees for consulting and travel: AstraZeneca; Advisory / Consultancy, Fees for consulting and equity: Shattuck Labs, Immunai; Licensing / Royalties, Patent filed by Memorial Sloan Kettering related to the use of tumor mutation burden to predict response to immunotherapy: PGDx. All other authors have declared no conflicts of interest.

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