Key points are not available for this paper at this time.
3016 Background: The immune checkpoint receptor programmed death-1 (PD-1) negatively regulates T-cell activation. In a phase I study, nivolumab, a PD-1 receptor blocking antibody, demonstrated durable clinical activity. Evaluation of the expression of the PD-1 ligand, PD-L1, by IHC with the 5H1 Ab suggested a correlation between pretreatment tumor PD-L1 expression and clinical response (Topalian et al, NEJM 2012). Methods: 304 pts with non-small cell lung cancer (NSCLC, n=127), melanoma (MEL, n=107), renal cell (RCC, n=34), colorectal (n=19) or prostate cancer (n=17) received nivolumab between 2008-2012 (0.1−10 mg/kg IV Q2W) during dose escalation and/or cohort expansion. Formalin-fixed paraffin-embedded tumor tissue and peripheral blood mononuclear cells (PBMC) were analyzed to explore potential pharmacodynamic/ predictive biomarkers associated with nivolumab therapy. Tumor surface PD-L1 expression was evaluated by IHC using an automated assay based on a sensitive and specific PD-L1 mAb (28-8) distinct from 5H1. PD-L1 positivity (PD-L1+) was defined as ≥5% cell membrane staining of any intensity. Lymphocyte subsets in PBMC were measured using flow cytometry. Results: Tumor membrane PD-L1 was measured in 101 MEL and NSCLC pts. 17/38 (45%) of MEL and 31/63 (49%) of NSCLC biopsies were PD-L1+. A numerically higher objective response rate (ORR), longer progression-free survival (PFS), and overall survival (OS) was seen with PD-L1+ in MEL pts (Table).Analysis of the association of PD-L1 expression with ORR, PFS and OS in NSCLC is ongoing. A correlative analysis of pt response with pre-/post-dose levels of lymphocytes will be presented. Conclusions: These data, using a novel, automated PD-L1 IHC assay and mAb, support the hypothesis of tumor PDL1+ predicting activity of nivolumab in advanced cancer, which is being prospectively assessed in phase III trials. Clinical trial information: NCT00730639. Table: see text
Grosso et al. (Mon,) studied this question.