Updated Overall Survival Data and Predictive Biomarkers of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Non-squamous NSCLC in the Phase III ORIENT-11 Study.

Abstract

INTRODUCTION\nSintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared to chemotherapy alone in non-squamous non-small cell lung cancer (NSCLC) in the ORIENT-11 study. Updated overall survival (OS) and PFS data and corresponding biomarker analyses are reported here.\n\n\nMETHODS\nIn this study, 397 previously untreated, locally advanced or metastatic non-squamous NSCLC patients received sintilimab plus chemotherapy (combo group) or placebo plus chemotherapy (chemo group). Patients were stratified by PD-L1 expression levels. Immune signature profiles from tumor RNA sequencing and PD-L1 immunohistochemistry were correlated with clinical outcome to identify predictive biomarkers.\n\n\nRESULTS\nAs of Jan 2021, with median follow-up of 22.9 months, median OS was significantly improved in the combo group compared to the chemo group (NR versus 16.8 months; HR 0.60, 95% CI: 0.45-0.79; p = 0.0003). High or medium immune cell infiltration was strongly associated with improved PFS in the combo group, in contrast to absent or low immune cell infiltration, which suggests that chemotherapy could not prime immune deserts to obtain benefit from PD-1 inhibition. In particular, high major histocompatibility complex (MHC) class-II presentation pathway expression was significantly correlated with prolonged PFS (HR=0.32, 95% CI: 0.19-0.54; p<0.0001) and OS (HR=0.36, 95% CI: 0.20-0.64; p=0.0005) in the combo group. Importantly, patients with low or absent PD-L1 but high MHC-II expression could still benefit from the combo treatment. In contrast, MHC class-I antigen presentation pathway was less relevant in this combination setting.\n\n\nCONCLUSIONS\nThe addition of sintilimab to chemotherapy demonstrated significantly longer OS in non-squamous NSCLC. Expression of MHC class-II antigen presentation pathway could identify patients benefitting most from this combination.