Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial

Abstract

Background: Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer.

Methods: We did this phase 2, single-arm trial at 27 sites (academic, hospital, and private cancer centres) in France, Germany, Italy, and USA. Patients who had received two or more previous treatments received intravenous nivolumab (3 mg/kg) every 2 weeks until progression or unacceptable toxic effects. The primary endpoint was the proportion of patients with a confirmed objective response as assessed by an independent radiology review committee. We included all treated patients in the analyses. This study is registered with ClinicalTrials.gov, number NCT01721759.

Findings: Between Nov 16, 2012, and July 22, 2013, we enrolled and treated 117 patients. 17 (14·5%, 95% CI 8·7-22·2) of 117 patients had an objective response as assessed by an independent radiology review committee. Median time to response was 3·3 months (IQR 2·2-4·8), and median duration of response was not reached (95% CI 8·31-not applicable); 13 (77%) of 17 of responses were ongoing at the time of analysis. 30 (26%) of 117 patients had stable disease (median duration 6·0 months, 95% CI 4·7-10·9). 20 (17%) of 117 patients reported grade 3-4 treatment-related adverse events, including: fatigue (five [4%] of 117 patients), pneumonitis (four [3%]), and diarrhoea (three [3%]). There were two treatment-associated deaths caused by pneumonia and ischaemic stroke that occurred in patients with multiple comorbidities in the setting of progressive disease.

Interpretation: Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment.

Funding: Bristol-Myers Squibb.

Conflict of interest statement

Declaration of interests

NAR has received personal fees from Bristol-Myers Squibb, Genentech, Roche, MedImmune, AstraZeneca, and Merck. TES has received research grant support from Bristol-Myers Squibb and personal fees from Genentech, Eli Lilly, Celgene, and Boehringer Ingelheim. SJA has received research grant support from MedImmune, and personal fees from Bristol-Myers Squibb, MedImmune, and AstraZeneca. LH has received research grant support from Astellas, has served as a non-paid consultant to Bayer and Xcovery, and has received personal fees from Bristol-Myers Squibb, Merck, Clovis, Helix Bio, and Genentech. HL has received personal fees from Bristol-Myers Squibb and Merck, and non-financial support from Bristol-Myers Squibb and Roche. BM has served as a consultant to Bristol-Myers Squibb and on advisory boards for Merck Sharp & Dohme. GAO has received research grant support from Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, New Link Genetics, Genentech, and Boehringer Ingelheim, and has received personal fees from Genentech and Boehringer Ingelheim. DRG has received research grant support from Bristol-Myers Squibb. BPL has received personal fees from Eli Lilly, Genentech, Pfizer, Biodesix, and Boehringer Ingelheim. GZ has received personal fees from Bristol-Myers Squibb. JW has received research grants from Boehringer Ingelheim, Novartis, Pfizer, Roche, and Bayer, and has served on advisory boards for and received lecture fees from Bristol-Myers Squibb, AstraZeneca, Boehringer Ingelheim, Clovis, Novartis, Pfizer, Roche, and Merck Sharp and Dohme. PJS has received personal fees, non-financial support, and support for clinical studies from Roche. FC has received personal fees from Bristol-Myers Squibb. CC has served as a consultant to Bristol-Myers Squibb, Merck, and Roche. RS has received research grant support and honoraria from and has served on advisory boards for Bristol-Myers Squibb. RMH has served on advisory boards for Bristol-Myers Squibb. CTH, CB, and BJL are employed by and own stock in Bristol-Myers Squibb. SSR has received research grant support and personal fees from Bristol-Myers Squibb and has received personal fees from Amgen, AstraZeneca, Aveo, Boehringer Ingelheim, Celgene, Genentech, Eli Lilly, and Novartis. SJA, DRG, AD, and SSR have received funding from the National Institutes of Health (USA). The other authors declare no competing interests.

Copyright © 2015 Elsevier Ltd. All rights reserved.

Figures

Figure 1. Best reduction of tumour size

Data are based on the IRC assessment of survival status in July, 2014. Includes patients with complete target lesion data, a baseline assessment, and at least one on-treatment assessment before progression or start of subsequent treatment (n=95). The line at −30% indicates the threshold for objective response per RECIST v1.1.

Figure 2. Changes of target tumour burden over time as assessed per IRC

Shows changes by RECIST response (A), in patients with an objective response (B), in patients with stable disease (C), and in patients with progressive disease or for whom response could not be determined (D). Includes patients with an evaluable response (n=100), who had a baseline assessment and at least one on-treatment tumour assessment. Tumour burden was measured as the sum of the longest diameters of target lesions. RECIST=Response Evaluation Criteria In Solid Tumors. SD=stable disease. PR=partial response. PD=progressive disease.

Figure 3. Kaplan-Meier analysis of progression-free survival (A) and overall survival (B)

Progression-free survival was IRC assessed.