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M.A. Socisnki



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    MINI 16 - EGFR Mutant Lung Cancer 2 (ID 130)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      MINI16.04 - Activity of Rociletinib in EGFR Mutant NSCLC Patients with a History of CNS Involvement (ID 965)

      16:45 - 18:15  |  Author(s): M.A. Socisnki

      • Abstract
      • Presentation
      • Slides

      Background:
      Rociletinib (CO-1686) is a novel, oral, irreversible tyrosine kinase inhibitor for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) with activity against the activating mutations (L858R and Del19) and the dominant acquired resistance mutation (T790M), while sparing wild-type EGFR. TIGER-X (NCT01526928) is a Phase I/II open-label, safety, pharmacokinetics and preliminary efficacy study of rociletinib in patients with advanced EGFR mutation-positive NSCLC with progressive disease after ≥1 EGFR tyrosine kinase inhibitor (TKI). An overall response rate of 67% has previously been reported in this trial for T790M positive patients treated with the 500 and 625 mg BID doses (Soria 2014). Here we provide preliminary data on the activity of rociletinib in the subgroup of patients with a history of CNS disease.

      Methods:
      Patients with a history of CNS disease were permitted if asymptomatic and stable, as defined by steroid requirements. The primary activity endpoint was RECIST overall response rate. However, patients who developed progressive disease (PD) while on study treatment were allowed to continue therapy with rociletinib if deemed clinically beneficial by the investigator.

      Results:
      As of 16 March 2015, a total of 401 patients received therapeutic dose levels of rociletinib (500, 625 and 750 mg BID) including 170 (42%) patients with a history of CNS metastases. Based on this interim analysis, the RECIST overall response rate among these patients with a history of CNS disease is 41%. To date, 42 patients with a history of CNS disease have continued therapy with rociletinib post-progression. Of those who continued for at least 14 days the average treatment duration beyond PD was 89 days (range: 14 - 336 days). Twenty-two of the 42 patients with a history of CNS disease with PD also received brain radiation and continued rociletinib treatment for an average of 120 days (range: 22 – 336 days) after PD. Rociletinib is held on radiation days only. Progression-free survival data for these subgroups is not yet mature. The three most common adverse events in the patient population with a history of CNS disease are similar to those found in the general TIGER-X patient population: hyperglycemia, diarrhea and nausea.

      Conclusion:
      In patients with a history of CNS disease, a factor associated with poor prognosis, rociletinib is active with a RECIST response rate of 41%. Local CNS radiation has been administered safely with rociletinib held on radiation days and continued afterwards. Prolonged use of rociletinib post CNS radiation suggests ongoing systemic benefit is still experienced by these patients. The role of rociletinib in NSCLC patients with CNS involvement is being further explored in the ongoing TIGER clinical development program.

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