Virtual Library

Start Your Search

X. Zhang



Author of

  • +

    Best of Posters - IASLC Selection - Part 1 (ID 262)

    • Event: WCLC 2013
    • Type: Exhibit Showcase Session
    • Track:
    • Presentations: 1
    • +

      P2.11-035 - Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients with non-small cell lung cancer (NSCLC) treated with nivolumab (Anti-PD-1; BMS-936558; ONO-4538) (ID 2372)

      09:55 - 10:25  |  Author(s): X. Zhang

      • Abstract
      • Slides

      Background
      The immune checkpoint receptor programmed death-1 (PD-1) negatively regulates T-cell activation upon interaction with its ligands, PD-L1 and PD-L2. In a Phase 1 dose-escalation/cohort expansion study (CA209-003; NCT00730639), nivolumab, a fully human PD-1 receptor blocking antibody, delivered durable responses in patients with solid tumors, including advanced NSCLC. Immunohistochemistry (IHC) analysis of tumor samples from this study suggested an association between pre-treatment tumor PD-L1 expression and clinical response to nivolumab in patients with melanoma (Grosso JF J Clin Oncol. 2013;31(suppl):abs 3016; Topalian SL NEJM 2012;366:2443-54). Here we investigate the association between PD-L1 expression by IHC and response to nivolumab in patients with NSCLC, and patient response with pre-/post-dose absolute lymphocyte counts (ALC) and selected lymphocyte cell subsets.

      Methods
      129 patients with NSCLC from the CA209-003 trial received nivolumab between 2008 and 2012 (1–10 mg/kg IV every 2 weeks) during dose escalation and/or cohort expansion. Archived formalin-fixed paraffin-embedded pre-treatment tumor tissue and pre-treatment and on-treatment peripheral whole blood samples were analyzed to explore potential pharmacodynamic/predictive biomarkers associated with nivolumab therapy. Pre-treatment tumor PD-L1 expression was evaluated by IHC using an automated assay developed by Dako based on a sensitive and specific anti-PD-L1 monoclonal antibody (28-8). Tumors were defined as PD-L1 positive (PD-L1+) when ≥5% of the tumor cells had membrane staining at any intensity. Lymphocyte subsets in the periphery were measured using flow cytometry.

      Results
      Tumor membrane PD-L1 expression was measured in 63 patients with NSCLC (29 squamous; 34 non-squamous). 31/63 (49%) NSCLC biopsies were PD-L1+. There was no apparent association between PD-L1 protein expression and NSCLC histology: for squamous and non-squamous tumors, 52% (15/29) and 47% (16/34) were PD-L1+, respective. Objective response rates for PD-L1+ and PD-L1- NSCLC patients with non-squamous and squamous histology are shown in the Table. Objective responses were observed in patients with squamous and non-squamous NSCLC who were negative for PD-L1 expression. Since increases in on-treatment ALC and activated T-cell phenotypes have been shown to positively associate with favorable clinical outcomes in ipilimumab monotherapy (Ku GY Cancer 2010;116:1767-75; Carthon BC Clin Cancer Res 2010;16:2861-71), results from an analysis correlating patient response with pre-/post-dose ALC and T-cell populations in patients with NSCLC receiving nivolumab will be presented.

      Table. Patient response according to PD-L1 expression status in patients with NSCLC
      Tumor type PD-L1 expression status Objective response rate, n/N (%)
      NSCLC (all patients) + 5/31 (16.1)
      4/32 (12.5)
      NSCLC (squamous) + 2/15 (13.3)
      3/14 (21.4)
      NSCLC (non-squamous) + 3/16 (18.8)
      1/18 (5.6)

      Conclusion
      Further evaluation of PD-L1 as a molecular marker of nivolumab therapy is required. Association of PD-L1 protein expression with clinical outcome is currently being prospectively assessed in ongoing Phase 3 trials. Clinical Trial Registration Number: NCT00730639

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.