Aims: Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, and ipilimumab, a fully human IgG1 Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) immune checkpoint receptor blocking antibody, have shown activity in advanced NSCLC; clinical data in melanoma showed improvement in survival and manageable safety profile when combined. We report interim results from phase I study evaluating first-line nivolumab + ipilimumab (N+I) combination in advanced NSCLC patients (pts). Methods: Chemotherapy-naïve pts (n=46) with squamous (sq) or non-sq NSCLC received the 3N+1Img/kg or 1N+3Img/kg combination dose IV every 3 weeks for 4 cycles followed by nivolumab 3mg/kg IV fortnightly until progression/unacceptable toxicity. Safety and Objective response rate (ORR; RECIST 1.1) were evaluated overall and by baseline tumour PD-ligand-1 (PD-L1) status (Dako immunohistochemistry assay).
Results: In the 4 cohorts with ≥4 months follow up, any-grade treatment-related adverse events (managed with protocol algorithms) were reported in 39 pts (85%; grade 3–4 in 22 pts [48%]) and led to discontinuation in 16 pts. Treatment-related deaths (n=3) were due to respiratory failure following colitis, bronchopulmonary hemorrhage and toxic epidermal necrolysis. Across all cohorts: 1+3mg/kg sq, 1+3mg/kg non-sq, 3+1mg/kg sq, 3+1mg/kg non-sq, the confirmed objective response rates (ORR) were 11%, 13%, 33% and 13%, respectively. Overall ORR (confirmed and unconfirmed) was 22% (median duration of response [mDOR] not reached [NR]) and stable disease (SD) 33% (range 22-56 weeks); 3 pts exhibited unconventional “immune related” responses. In 38 evaluable tumour samples from the study, ORR did not correlate with PD-L1 status. Conclusions: These interim data in pts with advanced NSCLC suggest that a nivolumab + ipilimumab immunotherapy regimen is feasible and demonstrates antitumor activity in both PD-L1+ and PD-L1– pts. Safety will be further assessed at additional specified doses and schedules.