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B. Vennapusa



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    OA05 - Treatment Advances in SCLC (ID 373)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      OA05.03 - Single-Agent Rovalpituzumab Tesirine, a Delta-Like Protein 3 (DLL3)-Targeted Antibody-Drug Conjugate (ADC), in Small-Cell Lung Cancer (SCLC) (ID 4648)

      14:20 - 15:50  |  Author(s): B. Vennapusa

      • Abstract
      • Presentation
      • Slides

      Background:
      SCLC is one of the most deadly malignancies. Rovalpituzumab tesirine (SC16LD6.5, Rova-T) is a first-in-class ADC directed against DLL3, a novel target identified in tumor initiating cells and expressed in over 80% of SCLC cases.

      Methods:
      Seventy-four patients with progressive SCLC after at least one previous systemic therapy were enrolled in a first-in-human study (NCT01901653), irrespective of DLL3 expression, including 68 at active doses of 0.2-0.4 mg/kg administered intravenously every 3 or 6 weeks. Available archived tumor tissue (n=48) was assessed retrospectively by immunohistochemistry for DLL3.

      Results:
      Among 60 evaluable subjects, active dose levels resulted in a confirmed objective response rate (ORR) of 18% and a confirmed clinical benefit rate (CBR; stable disease or better) of 68%. Among 26 evaluable subjects with DLL3 expression in at least 50% of tumor cells (DLL3-high), confirmed ORR and CBR were 39% and 89%, respectively. Median duration of response was 5.6 months. One-year survival rates among all and DLL3-high subjects were 18% and 32%, respectively. Among primary sensitive relapse patients, confirmed ORR and CBR among all subjects were 24% (8/33) and 67% (22/33); and among DLL3-high subjects were 53% (8/15) and 100% (15/15), with one-year survival rates of 17% and 33%, respectively. Among primary resistant/refractory relapse patients, confirmed ORR and CBR among all subjects were 12% (3/25) and 72% (18/25); and among DLL3-high subjects were 18% (2/11) and 73% (8/11), with one-year survival rates of 21% and 29%, respectively. The most common grade 3 or higher toxicities included thrombocytopenia (12%), serosal effusions (11%), and skin reactions (8%). ADC pharmacokinetics were linear with a terminal half-life of 10 - 14 days and anti-therapeutic antibodies did not develop

      Conclusion:
      Rovalpituzumab tesirine demonstrates encouraging single-agent anti-tumor activity with a manageable safety profile, including among patients with disease resistant or refractory to primary chemotherapy. Further development of rovalpituzumab tesirine in SCLC is warranted.

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    P2.01 - Poster Session with Presenters Present (ID 461)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P2.01-043 - Pathologist Agreement Rates of PD-L1 Tumor and Immune Cell Quantitation Using Digital Read, Field-Of-View, and Whole Tumor Image Analysis (ID 4041)

      14:30 - 15:45  |  Author(s): B. Vennapusa

      • Abstract

      Background:
      PD-L1 agents have shown clinical efficacy. Recent reports have demonstrated the predictive value of PD-L1 immunohistochemistry (IHC) assessment from immune (IC) and tumor cells (TC) in non-small cell lung carcinoma (NSCLC). While assessing percent staining of TC is a task familiar to pathologists, assessment of IC is novel and possibly challenging. As noted in other studies, digital pathology (DP) with image analysis (IA) has the potential to reduce inter-reader (IR) variation in specific situations. However, the impact of DP IA on IR variation in the setting of PD-L1 IHC scoring is unknown as are the effects of different IA approaches (field-of-view [FOV] vs whole tumor [WT]).

      Methods:
      A cohort of 60 NSCLC formalin-fixed paraffin-embedded tissue samples was stained with PD-L1 IHC (SP142). Three pathologists underwent training for IHC-based manual assay and DP IA interpretation. Three scorers independently and blindly scored each case using digital read (DR, no IA but digital assessment on computer monitor), FOV IA, and WT IA. Data was analyzed using pair-wise overall percent agreement rates (OPA) derived from assay threshold categorical bins.

      Results:
      For IC scoring, WT IA significantly improved IR agreement and reproducibility rates as compared to DR and FOV-based approaches (table 1). TC WT IA also showed similar improvements.

      TC-DR (%) TC-FOV (%) TC-WTA (%) IC-DR (%) IC-FOV (%) IC-WTA (%)
      R1-R2 83.1 (71.5-90.5) 89.8 (79.5-95.3) 98.3 (91.0-99.7) 89.1 (77.0-95.3) 91.5 (81.6-96.3) 100.0 (93.9-100.0)
      R2-R3 94.5 (85.1-98.1) 87.3 (76.0-93.7) 100.0 (93.5-100.0) 76.7 (62.3-86.8) 88.4 (75.5-94.9) 100.0 (93.5-100.0)
      R1-R3 82.1 (70.2-90.0) 85.7 (74.3-92.6) 98.2 (90.6-99.7) 83.9 (72.2-91.3) 95.5 (84.9-98.7) 100.0 (93.6-100.0)
      Table 1: NSCLC IR OPA rates. PD-L1 IHC scoring threshold 1% (TC1/IC1), R = Reader (95% confidence interval)

      Conclusion:
      Compared to DR and FOV IA, WT IA significantly improved pathologists’ PD-L1 IR rates for TC and IC scoring in NSCLC samples. Further studies regarding accuracy and reproducibility are being performed in a larger cohort.