First-line nivolumab (anti-PD-1; BMS-936558, ONO-4538) monotherapy in advanced NSCLC: Safety, efficacy, and correlation of outcomes with PD-L1 status.

8024 Background: The fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody nivolumab has demonstrated durable responses and tolerability in patients (pts) with previously treated advanced NSCLC. Tumor PD-1 ligand (PD-L1) expression is being studied as a potential biomarker for nivolumab. We report interim phase I results of first-line nivolumab in chemotherapy-naïve advanced NSCLC pts. Methods: Pts with squamous (sq) or non-sq advanced NSCLC received nivolumab 3 mg/kg IV Q2W until progression or unacceptable toxicity (post-progression treatment allowed based on protocol-defined criteria). Responses (RECIST 1.1) were evaluated overall and according to tumor PD-L1 status (PD-L1+ = ≥5% tumor cells expressing PD-L1 Dako immunohistochemistry assay). Results on the first 20 pts are included. Results: After ≥6 months follow up, 17 pts (85%) experienced any-grade treatment-related adverse events (AEs), managed with standard algorithms. Treatment-related grade 3-4 AEs (3 pts, 15%) were AST or ALT elevations, hyperglycemia, and rash (n=1 each). No pneumonitis (any grade) was observed. Objective response rate (ORR) was 30% (Table); 5/6 responders (83%) achieved response by first scan (wk 11). Two pts had >80% target lesion reduction at 18 wks. Of 15 evaluable tumor samples, 9 were PD-L1+. ORR was 67% in PD-L1+ pts; no responses were observed in the 6 PD-L1- pts. Responses were durable (median duration of response mDOR not reached NR; 5 ongoing responses). Conclusions: In this phase I study, nivolumab led to early, durable responses in advanced NSCLC pts, with a tolerable safety profile. PD-L1 status appeared to correlate with ORR/progression-free survival (PFS). Follow up and responses of 30 additional treated pts will be reported. These data support further studies of first-line nivolumab monotherapy in advanced NSCLC. Clinical trial information: NCT01454102. ORR mDOR Median PFS n/N (%) wk (range) All pts 6/20 (30) NR (11.1+, 37.7+) 29.6 (5.9, 47.6+) Non-sq 4/11 (36) NR (36.1, 37.7+) 45.6 (9.6, 47.6+) Sq 2/9 (22) NR (11.1+, 27.9+) 15.1 (5.9, 37.9+) PD-L1+ 6/9 (67) NR (11.1+, 37.7+) NR (8, 47.6+) PD-L1- 0/6 n/a 23.1 (9.6, 47.3+) PD-L1 unknown 0/5 n/a 15.1 (5.9, 35.7+)