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Jeffrey W. Clark



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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
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      OA12.02 - Updated Antitumor Activity of Crizotinib in Patients with MET Exon 14-Altered Advanced Non-Small Cell Lung Cancer (ID 13453)

      15:25 - 15:35  |  Author(s): Jeffrey W. Clark

      • Abstract
      • Presentation
      • Slides

      Background

      MET exon 14 alterations occur in ~3% of non-squamous non-small cell lung cancer (NSCLCs) and 20–30% of sarcomatoid lung carcinomas. Here we present updated antitumor activity for crizotinib in patients with advanced NSCLC whose tumors are positive for MET exon 14 alterations (hereafter MET exon 14-positive NSCLC), including updated biomarker analyses in circulating tumor DNA (ctDNA).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with MET exon 14-positive NSCLC by local molecular profiling were treated with 250 mg crizotinib BID in an expansion cohort of the ongoing PROFILE 1001 study (NCT00585195). Responses were based on derived investigator assessment per RECIST v1.0. Prospective plasma profiling for MET exon 14 alterations in plasma ctDNA was performed (PlasmaSELECT-R64; Personal Genome Diagnostics, Boston, MA).

      4c3880bb027f159e801041b1021e88e8 Result

      As of Jan 31, 2018, 69 patients (65 response-evaluable) with MET exon 14-positive NSCLC had been treated. Median age was 72 y (range: 34, 91). Tumor histology was: 84% adenocarcinoma, 9% sarcomatoid adenocarcinoma, 4% squamous cell carcinoma and 3% adenosquamous carcinoma. 61% were former-smokers, 38% never-smokers and 1% a current smoker. Median duration of treatment was 7.4 mo (95% CI: 5.5, 9.1), with 29% of patients ongoing. Confirmed responses were 3 CRs and 18 PRs (ORR, 32% [95% CI: 21, 45]); 29 patients had SD as their best overall response (Figure).

      crizo cmet ex14 waterfall_4may2018-v3.jpg

      Median time to response was 7.6 weeks (range: 3.7, 16.3). Median DOR was 9.1 mo (95% CI: 6.4, 12.7). Median PFS was 7.3 mo (95% CI: 5.4, 9.1). MET exon 14 alterations were detected in ctDNA from 18/37 (49%) patients with analyzable samples.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In patients with MET exon 14-positive advanced NSCLC, crizotinib treatment led to objective responses that were rapid and durable, with CRs in some cases. Plasma ctDNA profiling detected MET exon 14 alterations in a subset of patients who harbor MET exon 14 alterations by tumor testing.

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