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A.D. Johnson

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    OA 14 - New Paradigms in Clinical Trials (ID 681)

    • Event: WCLC 2017
    • Type: Oral
    • Track: Clinical Design, Statistics and Clinical Trials
    • Presentations: 1
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      OA 14.06 - Entrectinib in Patients with Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small Cell Lung Cancer (NSCLC) (ID 8564)

      11:00 - 12:30  |  Author(s): A.D. Johnson

      • Abstract
      • Presentation
      • Slides

      Entrectinib is a potent, investigational, CNS-active, oral inhibitor of ROS1 with a biochemical IC~50~ (0.2 nM) ~30 times more potent than crizotinib, the only agent approved for the treatment of ROS1-positive NSCLC. Previously, we reported an objective response rate of 85% in 13 ROS1 inhibitor-naïve NSCLC patients who were treated in Phase 1 studies (Drilon and Siena et al, Cancer Discov 2017), including 2 of 3 (67%) patients with CNS disease. Responses were durable, with 1 patient remaining on study for more than 3 years. Entrectinib was well tolerated, with predominantly Grades 1 or 2 adverse events that were reversible with dose modification.

      Patients with ROS1 inhibitor-naïve NSCLC were enrolled across Phase 1 and 2 studies of entrectinib. Patients were screened for ROS1 gene fusions either locally or centrally at Ignyta’s diagnostic laboratory using next generation sequencing. Entrectinib was administered orally at 600 mg once-daily in 4-week cycles. Safety was assessed by monitoring adverse events, laboratory tests, and clinic visits. Tumor assessments were performed at the end of Cycle 1 and every 8 weeks thereafter. All scans were read locally (INV) and by blinded independent central review (BICR) using RECIST v1.1. INV results will be presented except where noted.

      As of 24 May 2017, a total of 32 patients were evaluable for response (median age 52 years, 72% female). At a median follow-up of 12 months, objective responses were observed in 24 of 32 (75% [95% CI: 56.6, 88.5]; 3 complete responses) patients, including 7 of 11 (64% [95% CI: 30.8, 89.1]) patients with CNS disease at baseline. Five of 7 patients with evaluable CNS lesions by BICR experienced confirmed RECIST intracranial responses, for a CNS response rate of 71% (95% CI: 29.0, 96.3). With 19 (59%) patients remaining on study, the median duration of response was 17.2 months (95% CI: 6.5, 36.0) and progression-free survival was 19.1 months (95% CI: 6.5, 36.6). The most common (>15%) treatment-related adverse events were fatigue/asthenia (34%), dysgeusia (34%), dizziness (24%), weight increase (21%), paresthesia (19%), nausea (18%), constipation (18%), and diarrhea (16%). All data will be updated at the time of presentation.

      Entrectinib is well tolerated and has shown promising antitumor activity in ROS1 inhibitor-naïve NSCLC, including patients with CNS disease. Patients with ROS1+ NSCLC and other tumor types continue to be enrolled in STARTRK-2 (NCT02568267) in order to support a potential regulatory filing for entrectinib in this population.

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