Abstract CT126: Soluble HLA-G and -E (sHLA-G/E) as potential biomarkers of clinical outcomes in patients (pts) with advanced, refractory squamous (SQ) NSCLC treated with nivolumab (NIVO): CheckMate 063
Authors: Rebmann* Vera , Eberhardt* Wilfried E. , Rizvi Naiyer , Antonia Scott J. , Planchard David , Cappuzzo Federico , Mazières Julien , Zalcman Gérard , Lena Hervé , Wolf Jürgen , Horn Leora , Stinchcombe Thomas , Dy Grace , Blackwood-Chirchir Anne , Jin Chelsea , Geese William J. , Ramalingam Suresh S. ,   *Authors contributed equally to the current work
Published: July 2017

Abstract
Introduction: NIVO is a fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor providing long-term survival with a favorable safety profile and QoL benefit, approved for previously treated advanced/metastatic NSCLC. Although the likelihood of benefit from NIVO appears correlated with PD-L1 expression in non-SQ NSCLC, pts without PD-L1 may also benefit; this trend is not seen in SQ NSCLC. As sHLA-G/E are immunosuppressive molecules, we hypothesized that baseline peripheral sHLA-G/E may be associated with NIVO outcomes.
Methods: CheckMate 063 is a phase 2, single-arm study of NIVO in SQ NSCLC pts who progressed on/after prior platinum-based doublet chemotherapy (PT-DC). Of 117 pts treated, 50 had evaluable baseline serum and archived tumor samples. sHLA-G and -E serum levels (‘low’ defined as &lt;median; ‘high’ as ≥median) were measured by ELISA. Percent CD3+ and CD8+ T cells in tumor samples were evaluated by IHC.
Results: Pts achieving PR or SD had lower baseline sHLA-G and -E (Table). Pts with longer OS had low sHLA-G and -E. Median OS was 8.6 vs 6.0 mo (HR 0.58 [0.31, 1.09]) in pts with low vs high sHLA-G, respectively; median OS was 13.6 vs 4.6 mo (HR 0.52 [95% CI 0.27, 0.97]) in pts with low vs high sHLA-E. Longest OS occurred in pts with both low sHLA-G and -E (n=14; median OS 15.1 mo [4.57, not reached]). No correlation was seen between baseline sHLA-G and -E levels (Spearman’s r=0.18; P=0.22). High peripheral sHLA-G and -E were negatively correlated with CD3/CD8+ T-cell tumor microenvironment infiltration (CD3+ r=-0.39 and -0.26; CD8+ r=-0.40 and -0.24, respectively). sHLA-G and -E were not associated with smoking and ECOG performance status.
Table.Baseline sHLA-G and -E levels stratified by RECIST v1.1PR n=7SD n=3PD n=33bNE n=4PMedian sHLA-Ga4.687.5410.2921.140.41Median sHLA-Ea15.2511.3019.7330.830.39ang/mL; bn=32 for sHLA-ENE=non-evaluable; PD=progressive disease; PR=partial response; SD=stable disease
Conclusion: Lower baseline sHLA-G and -E levels in NIVO pts with advanced, refractory SQ NSCLC were associated with improved OS. Further studies are warranted to determine if sHLA-G/E are prognostic or predictive biomarkers in SQ and non-SQ NSCLC.
Citation Format: Vera Rebmann*, Wilfried E. Eberhardt*, Naiyer Rizvi, Scott J. Antonia, David Planchard, Federico Cappuzzo, Julien Mazières, Gérard Zalcman, Hervé Lena, Jürgen Wolf, Leora Horn, Thomas Stinchcombe, Grace Dy, Anne Blackwood-Chirchir, Chelsea Jin, William J. Geese, Suresh S. Ramalingam, *Authors contributed equally to the current work. Soluble HLA-G and -E (sHLA-G/E) as potential biomarkers of clinical outcomes in patients (pts) with advanced, refractory squamous (SQ) NSCLC treated with nivolumab (NIVO): CheckMate 063 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT126. doi:10.1158/1538-7445.AM2017-CT126