LBA4_PR: 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, by Solange Peters
Abstract 7128
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 = 396 | Chemo n = 397 | NIVOa 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 40 | 14.9 (12.7–16.7) - - 56 33 | 15.7 (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 = 187 | Chemo n = 186 | NIVO + 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 40 | 12.2 (9.2–14.3) - 51 23 | 15.2 (12.3–19.8) 0.78 (0.62–0.98) 59 35 |
All randomized pts | NIVO + IPI n = 583 | Chemo 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 40 | 13.9 (12.2–15.1) - 54 30 |
Study treatment only in PD-L1 ≥ 1% population;
b95% CI for NIVO vs chemo;
cstudy 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.
Resources from the same session
4627 - Niraparib therapy in patients with newly diagnosed advanced ovarian cancer (PRIMA/ENGOT-OV26/GOG-3012 study)
Presenter: Antonio González Martín
Session: Presidential Symposium I
Resources:
Abstract
Slides
Webcast
3955 - Phase III PAOLA-1/ENGOT-ov25 trial: Olaparib plus bevacizumab (bev) as maintenance therapy in patients (pts) with newly diagnosed, advanced ovarian cancer (OC) treated with platinum-based chemotherapy (PCh) plus bev
Presenter: Isabelle Ray-Coquard
Session: Presidential Symposium I
Resources:
Abstract
Slides
Webcast
2772 - VELIA/GOG-3005: Integration of veliparib (V) with front-line chemotherapy and maintenance in women with high-grade serous carcinoma of ovarian, fallopian tube, or primary peritoneal origin (HGSC)
Presenter: Robert Coleman
Session: Presidential Symposium I
Resources:
Abstract
Slides
Webcast
567 - Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis
Presenter: Suresh Ramalingam
Session: Presidential Symposium I
Resources:
Abstract
Slides
Webcast
Invited Discussant LBA1 and LBA2_PR
Presenter: Ana Oaknin
Session: Presidential Symposium I
Resources:
Slides
Webcast
Invited Discussant LBA4_PR
Presenter: Sanjay Popat
Session: Presidential Symposium I
Resources:
Slides
Webcast
Invited Discussant LBA5_PR
Presenter: Pasi Jänne
Session: Presidential Symposium I
Resources:
Slides
Webcast