Relationship of baseline tumoral IFNγ mRNA and PD-L1 protein expression to overall survival in durvalumab-treated NSCLC patients.

Abstract

3036 Background: Biomarkers may help to identify non-small cell lung cancer (NSCLC) patients (pts) more likely to have improved outcomes to anti-PD-L1 therapy. From 112 durvalumab (D)-treated pts, we previously reported that high pretreatment levels of PD-L1 protein and IFNγ mRNA expression in tumor biopsies were associated with higher objective response rates. We extend this analysis with mature survival outcome data that includes additional available pts; in addition, we examined changes in gene expression from on-treatment tumors in a subset of pts. Methods: CP1108/NCT01693562 was a nonrandomized phase 1/2 trial evaluating D in pts with advanced NSCLC or other solid tumors. As of 14 DEC 2015, 298 previously treated NSCLC pts received 10 mg/kg Q2W of D ≤12 mos with a median 16.1 mos follow up. Expression profiling of 100 immune-associated genes using Fluidigm Biomark on frozen biopsies and immunostaining for tumoral PD-L1 on fresh or archival biopsies was conducted. 157 pts (55% squamous; 54% ≥2 prior therapy lines) had matched baseline mRNA and PD-L1 data of sufficient quality. Samples with detectable levels of IFNγ mRNA were considered IFNγ+. Pts with ≥25% tumor cells stained for PD-L1 at any intensity were scored PD-L1+. Of the 157 pts, 32 pts had pre- and post-treatment tumors evaluable for 100-gene mRNA analysis. Results: Pts who were IFNγ+/PD-L1+ had a trend of longer overall survival compared to those who were IFNγ-/PD-L1-, even after adjusting for gender, age, prior therapy lines, histology, ECOG, and smoking (Table 1). Following treatment with D, the transcript most highly induced was IFNγ (~2-fold; p<0.016). Conclusions: NSCLC pts with elevated IFNγ mRNA and PD-L1 protein expression in baseline tumor biopsies may have longer survival with D treatment. D treatment induces IFNγ gene expression within the tumor microenvironment. Clinical trial information: NCT01693562.OS by IFNγ and PD-L1 status. # Pts (# events) Median in months (95% CI) Adjusted HRa; p IFNγ+/PD-L1+ 43 (11) NR (8.8, NA) 0.40; 0.016 IFNγ+/PD-L1‒ 20 (8) NR (6.5, NA) 0.38; 0.021 IFNγ‒/PD-L1+ 42 (16) 9.7 (5.1, NA) 0.64; 0.18 IFNγ‒/PD-L1‒ 52 (34) 5.9 (4.1, 10.2) NR=Not Reached; NA=Not Applicable; a Univariate log-rank p<0.05 for all adjusted p <0.05 (not shown)