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Charles C. Williams



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    P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.04-32 - Phase I/II Study of the A2AR Antagonist NIR178 (PBF-509), an Oral Immunotherapy, in Patients (pts) with Advanced NSCLC (ID 12495)

      16:45 - 18:00  |  Author(s): Charles C. Williams

      • Abstract
      • Slides

      Background

      Background: ATP is catabolized to adenosine in the tumor microenvironment, leading to excess adenosine and immunosuppressive effects via immune checkpoint protein adenosine 2A receptor (A2AR). NIR178 is an oral A2AR antagonist that selectively binds and inhibits A2AR, reactivating T cell-mediated antitumor immune response. This Phase I/II study evaluated NIR178 in previously treated pts with advanced NSCLC (NCT02403193).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Methods: Pts (ECOG PS 0─1) had received ≥1 prior line of therapy; EGFR/ALK pts had failed prior TKI therapy. Objectives: primary – determine MTD of single-agent NIR178; secondary – efficacy endpoints, PK, and evaluation of PD-L1 expression.

      4c3880bb027f159e801041b1021e88e8 Result

      Results: At 13 Dec 2017 data cut-off, 24 pts had been treated: median age 68 yrs, 46% male; 79% received prior immunotherapy; 22/24 (92%) pts had discontinued (due to progression [n=13], death [n=2], AEs [n=2] or other reasons [n=5]) and 2/24 (8%) pts remained on treatment. Dose levels evaluated: 80 (n=3), 160 (n=3), 320 (n=7), 480 (n=6), 640 mg BID (n=5). There was 1 DLT: Gr 3 nausea (640 mg). The most frequent (≥20%) any-Gr AEs regardless of causality were nausea (67%), fatigue (63%), dyspnea (46%), vomiting (33%), chest pain and other (29%), gastroesophageal reflux disease, anemia, diarrhea (all 25%), anorexia, back pain, generalized muscle weakness and cough (all 21%). Drug-related Gr 3 AEs were pneumonitis (8%) and nausea (4%); no Gr 4 AEs were reported. Potential immune-related any-Gr AEs were rash (8%), pneumonitis (8%), hypothyroidism, increased ALT/AST (all 4%). NIR178 systemic exposure (Cmax, AUC) increased more than proportionally with dose. Efficacy data for 17/24 treated pts demonstrated responses and SD across the dose range, including 1 confirmed CR (480 mg) and 1 PR (80 mg), both in immunotherapy-naïve pts. Durable SD >44 wks with tumor shrinkage was observed in 2 ongoing immunotherapy-exposed pts. Disease control was seen in pts with both high and low baseline PD-L1 expression.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Conclusions: NIR178 was well tolerated; AEs were manageable and there were no Gr 4 drug-related AEs. Immune-related AEs may indicate immune stimulation. Clinical benefit was observed in immunotherapy-exposed and -naïve pts irrespective of PD-L1 status.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.09-17 - A Call to Action: Rapid Collection of Post-Mortem Lung Cancer Tissue in the Community to Enable Lung Cancer Research (ID 12584)

      16:45 - 18:00  |  Author(s): Charles C. Williams

      • Abstract

      Background

      Posthumous rapid tissue donation (RTD) provides an opportunity to understand treatment-resistant lung cancers with preservation of valuable tumor and non-tumor specimens from primary and metastatic sites.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Consent to participate in the lung RTD program was obtained during patient care. When death occurred, tumor and paired non-tumor, cytology, and blood specimens were preserved as formalin-fixed and frozen specimens. Tissue sections were evaluated with hematoxylin and eosin (H&E) staining and programmed death ligand-1 (PD-L1) immunohistochemistry. Massively parallel sequencing was performed on 11 specimens.

      4c3880bb027f159e801041b1021e88e8 Result

      To date, 21 patients consented to participate in the RTD program. Post-mortem specimens (N=180) were preserved from 9 patients and the other patients remain alive. Evaluation of H&E slides confirmed well-preserved tissue. PD-L1 immunohistochemistry revealed heterogeneous expression between tumor sites. Next generation sequencing provided high quality data on all 11 tested samples.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Rapid donation of post-mortem tissue from lung cancer patients is feasible and provides high quality specimens for research. Post-mortem tissue collection of primary and metastatic tumors facilitates studies of tumor mutation evolution, mechanisms of drug resistance, and biomarker expression.

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