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Joyce Gakuria



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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-92 - Neoadjuvant Durvalumab With or Without Sub-Ablative Stereotactic Radiotherapy (SBRT) in Patients with Resectable NSCLC (NCT02904954) (ID 2945)

      10:15 - 18:15  |  Author(s): Joyce Gakuria

      • Abstract

      Background

      Preclinical evidence suggests that sub-ablative doses of radiation may have immunomodulating properties and may result in potent local and systemic anti-tumor immune-responses when combined with immune checkpoint-inhibitors (ICIs). Here we report the preliminary results of an ongoing phase-II trial of neoadjuvant therapy (NT) with Durvalumab alone or SBRT+Durvalumab followed by adjuvant Durvalumab for 12-months.

      Method

      Eligible patients were randomized to 2-cycles of Durvalumab (Arm-1) or 3 consecutive doses of SBRT(8GX3) plus 2-cycles of Durvalumab (Arm-2). Surgery was planned 1-2 weeks after last cycle of Durvalumab. Primary endpoint was DFS for both arms versus historical controls. Secondary endpoints were safety and efficacy determined by clinical/pathological response rates. We compared tumor immunephenotype (IP) in pre- and post-treatment samples by XCell deconvolution of RNAseq transcriptomic data.

      Result

      34 patients were randomized (1/1/17-1/11/19,). Patients in Arm-2 were more frequently ever-smokers and had more PD-L1+ve tumors (Table). All patients completed NT. Grade 3/4 adverse events (AEs) occurred in 4 patients after NT (3 in Arm-1, 1 in Arm-2). One patient (Arm-1) died preoperatively from an unrelated stroke. 32 patients were surgically explored and 30 resected (28R-0:87%). There were no perioperative deaths. Grade 3/4 perioperative AEs occurred in 10/32 patients (31%). In Arm-2, 8/17 (47%) patients had a major pathologic response (MPR: £10% residual tumor) compared to none in Arm-1. Excluding 4 patients with EGFR mutations, MPR occurred in 8/13(61.5%) patients in Arm-2. Relative to Durvalumab alone, SBRT+Durvalumab was associated higher abundance of dendritic cells, myeloid cells and fibroblasts. In Arm-2, tumors with MPR had a higher immunoscore and greater abundance of dendritic cells and higher HLA gene expression.

      Conclusion

      In this randomized-trial, neoadjuvant Durvalumab with or without SBRT was well tolerated. The rates of MPR after SBRT+Durvalumab are promising and suggest that sub-ablative doses of radiation may significantly enhance local immune response.

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