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    Mini Oral session I (ID 60)

    • Event: ELCC 2019
    • Type: Mini Oral session
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 4/11/2019, 08:00 - 08:50, Room A
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      111O - Activity of larotrectinib in TRK fusion lung cancer (ID 378)

      08:00 - 08:50  |  Author(s): Lee Rosen

      • Abstract
      • Presentation
      • Slides

      Background

      Tropomyosin receptor kinases (TRK) fusions involving NTRK1, NTRK2 and NTRK3 genes occur in a diverse range of tumor types including lung cancer. Larotrectinib, the first FDA-approved selective TRK inhibitor, has demonstrated an overall response rate of 75% by independent central review across a broad range of tumor types (Drilon et al., NEJM 378:731-9, 2018). Here we report on the subset of lung cancer patients that have been treated with larotrectinib.

      a9ded1e5ce5d75814730bb4caaf49419 Methods

      NSCLC patients with TRK fusion cancer detected by molecular profiling from two clinical trials (NCT02122913 and NCT02576431) were eligible. Larotrectinib (100 mg BID) was administered on a continuous 28-day schedule until withdrawal, unacceptable toxicity or disease progression. Efficacy was investigator assessed using RECIST version 1.1.

      20c51b5f4e9aeb5334c90ff072e6f928 Results

      As of July 30, 2018 eleven patients with metastatic lung adenocarcinoma were enrolled. Median age was 52 years (range 25 – 76). Eight patients had fusions involving NTRK1 and diverse fusion partners; EPS15 (n = 2), TPM3 (n = 2), IRF2BP2 (n = 2), TPR (n = 1), SQSTM1 (n = 1). Three patients had fusions involving NTRK3; fusion partners SQSTM1 (n = 2) and ETV6. Ten patients had prior systemic therapy (5 patients had 3 or more prior therapies) with best response on last prior therapy being 1 partial response and 4 stable disease. Seven patients were evaluable for response to larotrectinib. One patient had a complete response, 4 patients had a partial response, and 2 patients had stable disease (ORR 71%). The median time to response was 1.8 months. The duration of response ranged from 7.4+ months to 17.6+ months; the median duration of response was not reached. Two patients discontinued treatment due to disease progression and 1 withdrew consent. Four patients were on treatment less than 1 month and were non-evaluable for efficacy. Larotrectinib was well tolerated, with treatment related adverse events being predominantly grade 1 and grade 2.

      fd69c5cf902969e6fb71d043085ddee6 Conclusions

      Larotrectinib is highly active in lung cancer patients harboring NTRK gene fusions. These results strongly support the inclusion of NTRK gene fusions as part of routine molecular testing for patients with lung cancer.

      b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification

      NCT02122913, NCT02576431.

      7a6a3ffa2dadc03a6151ee2c4d6fa383 Legal entity responsible for the study

      Loxo Oncology Inc. Bayer AG.

      213f68309caaa4ccc14d5f99789640ad Funding

      Loxo Oncology Inc. Bayer AG.

      682889d0a1d3b50267a69346a750433d Disclosure

      A. Drilon: Honoraria: Ignyta, Loxo, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Genentech, Roche, Takeda, ARIAD, Millenium, Helsinn, Beigene, BerGenBio, Hengrui Therapeutics, Exelixis, Bayer, Tyra Biosciences; Research: Foundation Medicine. V. Moreno: Educational grant: Medscape/Bayer. U. Lassen: Honorarium: Bayer. L. Rosen: Research funding: Loxo Oncology. B.H. Childs, S. Nanda: Employee: Bayer Healthcare Pharmaceuticals. M.C. Cox, N.C. Ku: Employee: Loxo Oncology. A.F. Farago: Consulting: Bayer; Consulting, research funding: Loxo, AstraZeneca, Genentech, Pharmamar, AbbVie & Stemcentrx; Research funding: Ignyta, Merck, BMS. All other authors have declared no conflicts of interest.

      cffcb1a185b2d7d5c44e9dc785b6bb25

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