Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients (pts) with advanced solid tumors treated with nivolumab (anti-PD-1; BMS-936558; ONO-4538).

Abstract

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]

PD-L1 and PD-1 and characterization of tumor-infiltrating lymphocytes in high grade sarcomas of soft tissue – prognostic implications and rationale for immunotherapy

“…In the present study, we report absolute percentages of PD-L1 positivity without applying pre-set cut-offs as suggested by several large studies. [34][35][36][37][38] In addition, we used the PD-L1 antibody clone SP263 for immunohistochemistry, which has been recommended as companion diagnostic in previous studies targeting PD-1/PD-L1 axis. 7,39,40 To avoid possible confounding effects of preoperative treatment on tumor immunology and TME, we included exclusively primary resected, therapy-na€ ıve hSTS in our study.…”

Tumor Lysate‐Loaded Lipid Hybrid Nanovaccine Collaborated with an Immune Checkpoint Antagonist for Combination Immunotherapy

“…The antagonist may not be strong enough as an alternative to immune checkpoint antibody. Lastly, it showed in recent clinical research that the objective response rate of anti‐PD‐1 or anti‐PD‐L1 therapy was below expectation in some patients, which may be attributed to that the immune response in tumor microenvironment is really complex and dynamic . Altogether, the nanovaccine may need to develop further combination with other therapeutic modality in the future.…”

Long‐term efficacy and predictive correlates of response to nivolumab in Japanese patients with esophageal cancer

“…Regarding the relationship between PD‐L1 expression and nivolumab efficacy, many studies have reported relationships between treatment benefit with nivolumab and PD‐L1 expression levels 16,19,20 . One study, using a 5% expression threshold, showed the potential of pretreatment PD‐L1 tumor expression as a predictive marker to indicate which patients would benefit from treatment 19 .…”