Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) 
monotherapies have shown promising clinical activity in advanced, refractory 
non-small-cell lung cancer (NSCLC), but antitumor activity appears to be greater 
in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) 
tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic 
T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor 
activity in patients with advanced NSCLC, regardless of PD-L1 tumor status. 
ARCTIC (NCT02352948) is a global, phase III, randomized, open-label multicenter 
study in patients with advanced NSCLC assessing the safety and clinical activity 
of durvalumab versus standard of care (SoC; erlotinib, gemcitabine, or 
vinorelbine) in patients with PD-L1(+) tumors (≥25% of tumor cells with membrane 
staining using VENTANA PD-L1 [SP263] CDx Assay) (Sub-study A) and the 
combination of durvalumab + tremelimumab or either agent as monotherapy versus 
SoC in patients with PD-L1(-) tumors (Sub-study B). Eligible patients are those 
with locally advanced or metastatic NSCLC (Stage IIIB/IV), without epidermal 
growth factor receptor tyrosine kinase activating mutations or anaplastic 
lymphoma kinase rearrangements, who have received at least 2 prior systemic 
regimens, including 1 platinum-based chemotherapy regimen. Co-primary endpoints 
are progression-free survival and overall survival. Secondary endpoints include 
the proportion of patients alive at 12 months, objective response rate, duration 
of response, progression-free survival at 6 and 12 months, safety and 
tolerability, pharmacokinetics, immunogenicity, and quality of life. The 
exploratory endpoints will assess potential biomarkers of treatment response. 
Recruitment started in January 2015 and is ongoing.