Author of

• 17842

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  P2.06 - Poster Session with Presenters Present (ID 467)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 17870

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    P2.06-028 - A Phase 2 Study of Prexasertib in Patients with Extensive Stage Small Cell Lung Cancer (ID 4176)

    14:30 - 14:30  |  Author(s): L. Golden
    • Abstract

    Background:
    Checkpoint kinase 1 (CHK1), plays a role in cell cycle regulation and DNA damage repair. Prexasertib monomesylate monohydrate (prexasertib, or LY2606368) inhibits CHK1 and induces replication catastrophe. As monotherapy, it demonstrated an acceptable safety profile and preliminary evidence of efficacy in Phase 1. Replication stress, together with defects in cell cycle checkpoints and/or DNA damage repair pathways may sensitize tumors to CHK1 inhibitors. Small cell lung cancer (SCLC) tumors have high levels of replication stress through mechanisms such as MYC amplification and high rates of TP53 mutations, RB1 loss, and genomic rearrangements. Preclinical models of SCLC demonstrate sensitivity to prexasertib monotherapy. As a result, prexasertib is an attractive agent to evaluate in patients with SCLC.
    
    Methods:
    This is a parallel cohort, non-randomized, open-label, multicenter Phase 2 study (NCT02735980) in patients with extensive disease (ED)-SCLC. Cohort 1 includes patients with platinum-sensitive disease (objective response to prior platinum-based therapy with subsequent progression ≥90 days after last platinum dose). Cohort 2 includes patients with platinum‑resistant/refractory disease (patients who either did not have an objective response to prior platinum-based therapy or had progression <90 days after last platinum dose). The primary objective is best overall response rate per cohort as determined per RECIST v1.1. Secondary objectives include evaluation of safety/toxicity, pharmacokinetics, and efficacy measures; which include overall survival, progression-free survival, duration of response, and disease control rate. Safety will be assessed by collecting and grading AEs as per CTCAE v4.0. Exploratory biomarkers associated with efficacy and safety of prexasertib may also be assessed. Key inclusion criteria include: patients ≥18 years having histologic or cytologic diagnosis of ED‑SCLC who received prior platinum therapy; ≥1 measurable lesion per RECIST v1.1; ECOG performance status of 0 or 1; discontinued prior therapies ≥14 days before first dose of prexasertib. Key exclusion criteria include: received ≥2 prior therapies for ED-SCLC; symptomatic CNS metastases, prior treatment with CHK1 inhibitor; or serious cardiac conditions. Prexasertib will be administered as intravenous infusion every 14 days. Disease will be assessed by radiographic imaging every 6 weeks. Approximately 116 patients (58 per cohort) are planned for enrollment in 10 countries (>60 sites). An interim futility analysis will be conducted in each cohort after 29 patients have completed cycle 3 and, if required, the response is confirmed. Enrollment began in May 2016.
    
    Results:
    Section not applicable.
    
    Conclusion:
    Section not applicable.