A randomized phase II study comparing nivolumab (NIVO) with carboplatin-pemetrexed (CbPEM) for patients (pts) with EGFR mutation-positive non-small cell lung cancer (NSCLC) who acquire resistance to tyrosine kinase inhibitors (TKIs) not due to a secondary T790M mutation (WJOG8515L).

Abstract

9037 Background: Although the efficacy of antibodies to programmed cell death–1 (PD-1) appears to be less pronounced in patients with NSCLC harboring epidermal growth factor receptor gene ( EGFR) mutations, patients who develop disease progression (PD) to TKIs due to mechanisms other than secondary T790M mutation of EGFR might be more likely to benefit from NIVO. Here, we report the results of first randomized phase II trial to compare NIVO with the CbPEM in those population. Methods: Pts with advanced EGFR mt NSCLC who experienced PD after EGFR-TKIs were randomized 1:1 to NIVO or CbPEM. Eligibility criteria included the treatment history with TKIs as follow; no evidence of T790M after PD on 1st/2nd generation (gen) TKIs (A) after PD on 3rd gen TKIs as a 2nd line for T790M positive tumor (B) or 3rd gen TKIs as a front-line (C). The primary end point is progression-free survival (PFS) and biomarker analysis were included for exploratory analysis. Results: A total of 102 patients was randomized. Median PFS and overall survival (OS) were 1.7 and 20.7 months (mo), respectively, for NIVO arm (n = 52) versus 5.6 and 19.9 months for CbPEM (n = 50) (Hazard ratio [HR] = 1.92 and 0.88, respectively). Overall response rate and duration of response were 9.6% and 5.3 months for NIVO and 36.0% and 5.5 months for CbPEM. PD-L1 expression on tumor cells and tumor mutation burden (TMB) were evaluated in 77 (TPS 0%. 1-49%, > 50%, n = 46, 20, and 11) and 50 (Median TMB 6.2mt/mb). Immune-related gene expression profiling was under evaluation and the results will be demonstrated in the meeting. The efficacy of NIVO in PD-L1 strong positive (>50%, n = 8) and no evidence of T790M after PD on 1st/2nd gen TKIs (n = 29) was tended to be better than their counterparts. There was no significant correlation between TMB and the efficacy of NIVO. Pneumonitis was observed in one patient (1.0%) for NIVO arm and no new safety signals were noted. Conclusions: NIVO was not associated with longer PFS than CbPEM in selected pts with advanced EGFR mt NSCLC. OS was similar between groups. Baseline PD-L1 status and genetic alteration features may be relevant predictive markers to select pts who would benefit from NIVO. Clinical trial information: jRCTs051180133. [Table: see text]