Background: Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, and ipilimumab, an IgG1 CTLA-4 checkpoint receptor blocking antibody, have shown activity in advanced NSCLC; clinical data in melanoma showed improved responses and a manageable safety profile when combined. We report interim results from a phase I study evaluating first-line nivolumab + ipilimumab (N+I) in advanced NSCLC patients (pts). Methods: Chemotherapy-naive pts (n=46) with squamous (sq) or non-sq NSCLC received the 3 + 1 mg/kg or 1 + 3 mg/kg combination dose IV Q3W for 4 cycles followed by nivolumab 3 mg/kg IV Q2W until progression/unacceptable toxicity. Objective response rate (ORR; RECIST 1.1) was evaluated overall and by baseline tumor PD-L1 status (Dako immunohistochemistry assay). After an amendment, a 1 + 1 mg/kg cohort was added (n=30, data immature at Dec 2013 analysis). 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, bronchopulmonary hemorrhage and toxic epidermal necrolysis. Responses occurred in all 4 cohorts (Table); overall ORR^b was 22% (median duration of response [mDOR] not reached [NR]) and stable disease (SD) 33% (range 13 – 34.1+ wks); 2 pts exhibited unconventional “immune related” responses. In 29 evaluable tumor 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 the 1 + 1 mg/kg dose. The recommended combination dose for phase II/III evaluation has not been determined. Clinical trial information: NCT01454102.

^a Confirmed OR only. ^b Confirmed + unconfirmed OR.