Author of

• 25909

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  OA12 - Novel Therapies in MET, RET and BRAF (ID 921)

  • Event: WCLC 2018
  • Type: Oral Abstract Session
  • Track: Targeted Therapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 15:15 - 16:45, Room 106

  • 26108

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    OA12.01 - Phase II Data for the MET Inhibitor Tepotinib in Patients with Advanced NSCLC and MET Exon 14-Skipping Mutations (ID 12896)

    15:15 - 15:25  |  Author(s): Hiroshi Sakai
    • Abstract
    • Presentation
    • Slides

    Background
    

    A subset (3%) of NSCLCs harbor mutations of the MET proto-oncogene that cause MET exon 14 skipping (METex14) and accumulation of active MET lacking a juxtamembrane domain. We report interim data from a single-arm phase II trial (NCT02864992) investigating the efficacy and safety of the potent, selective tyrosine-protein kinase MET inhibitor tepotinib in patients with METex14-skipping mutation-positive (METex14+) NSCLC.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Recruitment of ≤120 adult patients with advanced METex14+ NSCLC without EGFR-activating mutations or ALK rearrangements is ongoing. METex14+ mutations are identified in FPE tumor (T) material and/or plasma (L; 60 patients each, overlap anticipated) by a central laboratory. Patients receive tepotinib 500mg QD until disease progression, intolerable toxicity, or withdrawal. Primary endpoint: objective response rate (ORR). Secondary endpoints include safety.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Forty-one patients have been treated to date; data are available for 34 (median age 73.5 years; 23 male; 24/8 Caucasian/Asian; prior lines of therapy: 0, n=12; 1, n=11; 2, n=10; 3, n=1; stage IVA, n=4; stage IV, n=29; stage IIIB, n=1). Treatment is ongoing in 24 patients. Based on investigator assessment, 13/22 (59.1%) evaluable patients responded: 1 had a confirmed complete response; 12 had a confirmed partial response (PR); 3 (13.6%) had stable disease for ≥12 weeks (SD). Based on independent review, 9/22 (40.9%) had a confirmed PR; 5 (22.7%) had SD. Duration of response >12 months in 2 patients. Twenty (58.8%) patients have experienced tepotinib-related treatment-emergent adverse events (TRTEAEs), including serious TRTEAEs in 3 (8.8%): pneumonia =1, generalized oedema=1, interstitial lung disease=1, and grade ≥3 TRTEAEs in 6 (17.6%): generalized oedema=1, pneumonia=1, ALT increased=1, AST increased=1, amylase increased=2, gamma GT increased=1, lipase increased=1, hyperkalemia=1; no TRTEAEs were grade ≥4 or led to death. Five (14.7%) patients have died.

    

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Tepotinib 500mg QD has promising activity in METex14+ NSCLC, with a favorable safety profile.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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