Safety and response with nivolumab (anti-PD-1; BMS-936558, ONO-4538) plus erlotinib in patients (pts) with epidermal growth factor receptor mutant (EGFR MT) advanced NSCLC.

8022 Background: Erlotinib is FDA-approved for the first-line treatment of EGFR MT NSCLC, with a median progression free survival (PFS) of 10.4 months. Nivolumab, a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, demonstrated encouraging safety and survival outcomes as monotherapy in advanced NSCLC pts. Preclinical data support EGFR pathway activation of PD-L1 expression and immune escape in EGFR driven lung tumors. Interim results from a phase I study evaluating nivolumab + erlotinib in an EGFR MT advanced NSCLC cohort are reported. Methods: Stage IIIB/IV EGFR MT chemotherapy-naïve NSCLC pts (EGFR TKI naïve or progression post prior TKI therapy) received nivolumab 3 mg/kg IV Q2W + erlotinib 150 mg PO daily until progression/unacceptable toxicity. Objective response rate (ORR) and PFS were evaluated by RECIST 1.1. Results: All pts (n=21) began study treatment ≥10 months prior to data analysis; only 1 pt was EGFR TKI naïve. Any-grade treatment-related AEs were reported in all 21 pts; treatment-related grade 3–4 AEs (4 pts) were increased AST (n=2) or ALT (n=1), weight decrease and diarrhea (1 pt each); 2 pts discontinued due to treatment-related AEs (grade 3 AST increase and grade 2 nephritis). No pneumonitis (any grade) was observed. ORR was 19% (4/21 pts) and 24 wk PFS rate was 47%; median duration of response (DOR) was not reached (range 6.1+ to 27.1+ wks). Of the 20 pts with acquired erlotinib resistance, 3 (15%) achieved partial response (PR, all ongoing; DOR 6.1+, 16.3+ and 27.1+ wks); 9 pts (45%) had stable disease with 3/9 (33%) ongoing (time to progression/death 9.9+, 15.7, 21, 22.3, 24.4+, 31.1+, 35.9, 52.7 and 53 wks), and 1 pt had an unconventional “immune related” response (ongoing), with 46% reduction in target lesions after progression in non-target lesions. The EGFR TKI-naïve pt achieved PR with DOR 24.3+ wks (ongoing). Conclusions: These interim results suggest that nivolumab + erlotinib may provide durable clinical benefit and an acceptable safety profile in TKI refractory, EGFR MT advanced NSCLC, supporting further evaluation of nivolumab in pts with EGFR MT NSCLC. Additional follow up will be presented. Clinical trial information: NCT01454102.