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A. Koustenis

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    P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
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      P1.01-080 - Treatment Rationale and Study Design for the Phase 3 JUNIPER Study: Abemaciclib vs Erlotinib in Patients with Stage IV NSCLC and KRAS Mutation (ID 1438)

      09:30 - 17:00  |  Author(s): A. Koustenis

      • Abstract
      • Slides

      Abemaciclib (LY2835219) is a potent, selective small molecule inhibitor of CDK4/6, which has been shown to inhibit cell cycle progression by preventing the phosphorylation and functional inactivation of the Rb tumor-suppressor protein. Cell cycle dysfunction due to abnormalities in the CDK4/6 pathway occurs in NSCLC. KRAS mutant xenografts predict for greater sensitivity to CDK4/6 inhibitors. In a phase 1 study with abemaciclib (Goldman ASCO 2014), 16 patients with KRAS mutant tumors (N=29) had a response of stable disease (SD) or better (disease control rate [DCR]=55.2%), and 9 patients with KRAS wild-type tumors (N=24) had a response of SD or better (DCR=37.5%).

      JUNIPER (NCT02152631) is a randomized, phase 3 study of abemaciclib (200 mg orally q12hrs) + best supportive care (BSC) versus erlotinib (150 mg orally q24hrs) + BSC in patients with stage IV NSCLC whose tumors have detectable KRAS mutations and who have progressed after platinum-based chemotherapy and one other prior therapy or who are not eligible for further chemotherapy. About 550 patients will be randomized to abemaciclib or erlotinib 3:2 ratio using following factors: number of prior chemotherapy regimens (1 vs. 2), ECOG PS (0 vs. 1), gender (male vs. female) and KRAS mutation (G12C vs. others). This design has 80% power to detect overall survival (OS) hazard ratio (HR) of 0.75 (type I error 0.045) and progression-free survival (PFS) HR of 0.67 (type I error 0.005). Erlotinib was chosen as the control arm, as it is the only agent indicated for both 2nd and 3rd line therapy in advanced NSCLC. Treatment will continue until disease progression or unacceptable toxicity occurs, with assessments every 28 days, followed by short-term and long-term follow-up. Primary objectives are to compare OS and PFS of the treatment arms. Enrollment began December 2014. If the primary objectives are achieved, this study will provide results on an alternative treatment option, abemaciclib + BSC, for patients with NSCLC whose tumors have detectable KRAS mutations, currently a patient population with few treatment options.

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