Nivolumab (anti-PD-1, BMS-936558, ONO-4538) in patients (pts) with advanced non-small-cell lung cancer (NSCLC): Survival and clinical activity by subgroup analysis.

8112^ Background: Nivolumab, a fully human IgG4, PD-1 immune-checkpoint inhibitor antibody, has shown durable clinical activity in a large phase I trial of pts with advanced solid tumors. For NSCLC pts in this trial, we report overall survival (OS) by dose and histology and clinical activity of pt subgroups including PD-L1 tumor status. Methods: Previously treated pts with advanced NSCLC received IV nivolumab (1, 3, or 10 mg/kg) Q2Wk for ≤96 wk with tumor evaluation by RECIST v1.0. Clinical activity by key prognostic factors was assessed. PD-L1 tumor cell membrane expression was measured in archival specimens (n=68) by a Dako immunohistochemistry assay (positive ≥5% tumor cells). Results: Across doses and histologies, NSCLC pts (N=129, 54% with ≥3 prior therapies) hadmedian overall survival (mOS) of 9.2-14.9 mo and 1- and 2-y OS rates of 32-56% and 12-45%, respectively (Table). At the 3 mg/kg dose, mOS was 14.9 mo; 1- and 2-y OS rates were 56% and 45%. Objective response rate was 17% (22/129); median response duration was 17 mo. Clinical activity was observed across all pt subgroups, including <3 and ≥3 prior therapies and with/without EGFR or KRAS mutations. For pts with PD-L1(+) and (–) tumors, mOS was 7.8 mo (95% CI: 5.6, 21.7) and 10.5 mo (5.2, 21.2), respectively; mPFS was 3.6 mo (1.8, 7.5) and 1.8 mo (1.7, 2.3). Grade 3-4 treatment-related adverse events occurred in 14% of pts; most common was fatigue (3%). Conclusions: Nivolumab continues to demonstrate an encouraging survival profile and clinical activity across NSCLC pt subgroups with a manageable safety profile. Ongoing phase III trials are evaluating 3 mg/kg nivolumab in NSCLC pts and PD-L1 as a potential predictor of clinical outcomes. Clinical trial information: NCT00730639. Pts mOS,* mo (95% CI) OS rate,* % (95% CI) [pts at risk] 1-Y 2-Y All† n=129 9.9 (7.8, 12.4) 42 (34, 51) [48] 24 (16, 32) [20] 1 mg/kg n=33 9.2 (5.3, 11.1) 32 (16, 49) [8] 12 (3, 27) [2] 3 mg/kg n=37 14.9 (7.3, NR) 56 (38, 71) [17] 45 (27, 61) [9] 10 mg/kg n=59 9.2 (5.2, 12.4) 40 (27, 52) [23]) 19 (10, 31) [9] Squamous n=54 9.2 (7.3, 12.5) 40 (27, 54) [19] 24 (13, 37) [9] Nonsquamous n=74 10.1 (5.7, 13.7) 43 (32, 54) [28] 23 (13, 34) [10] Abbreviation: NR, not reached. *Sept 2013 analysis. †One pt had unknown histology.