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W. Jeong



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    MINI 30 - New Kinase Targets (ID 157)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI30.02 - Phase II Study of Defactinib, VS-6063, a Focal Adhesion Kinase (FAK) Inhibitor, in Patients with KRAS Mutant Non-Small Cell Lung Cancer (NSCLC) (ID 2875)

      18:30 - 20:00  |  Author(s): W. Jeong

      • Abstract
      • Presentation
      • Slides

      Background:
      KRAS mutations, which occur in approximately 30% of lung adenocarcinoma cases, represent a major unmet clinical need in thoracic oncology. Preclinical studies have demonstrated that KRAS mutant NSCLC cell lines and xenografts with additional alterations in either p53 or INK4a/Arf (CDKN2A) are sensitive to FAK inhibition. Defactinib (VS-6063) is a selective oral inhibitor of FAK. This trial examined the effect of FAK inhibition in patients with KRAS mutant NSCLC and various permutations of p53 and CDKN2A alterations.

      Methods:
      This multi-center, non-randomized, open-label, multi-cohort trial enrolled patients with advanced KRAS mutant NSCLC who had received at least one prior (platinum-based chemotherapy doublet) line of therapy. The primary endpoint was progression-free survival (PFS) at 12 weeks. Patients were enrolled into one of four cohorts defined by INK4a/Arf and p53 status. In all cohorts, patients received defactinib 400 mg orally BID until disease progression.

      Results:
      Fifty-three patients with KRAS mutant NSCLC were enrolled across 9 US sites as of the data cut-off date (13-Mar-2015). Forty-seven patients were enrolled to one of the four molecularly defined cohorts. The median age was 62 years (range 33-80); 48% were female. The median number of prior lines of therapy was 3 (range 1-8) 15 (28%) pts met the 12 week PFS endpoint, with one patient achieving a PR. Median PFS was 46 days (range 12-205 days). Eight patients remained on study as of the data cut-off date. Clinical efficacy did not correlate with secondary mutation status across this KRAS mutant population. Adverse events considered at least possibly related to defactinib were experienced by 35 pts (76%). The majority of these were grade 1 or 2. 11 patients (24%) experienced at least possibly related grade 3-5 events, including 2 grade 5 respiratory failure events. Underlying disease was a confounding factor in many pts. The most commonly reported treatment emergent adverse events of any grade were fatigue (24%) and increased bilirubin (24%).

      Conclusion:
      In pretreated pts with KRAS mutant NSCLC defactinib demonstrates promising clinical activity with disease control rates comparable to other molecularly targeted agents for this pt population. Defactinib was generally well tolerated. Further development is warranted. Clinical trial: NCT01778803.

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