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Jean-François Martini



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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-06 - First-Line Lorlatinib Versus Crizotinib for Advanced Anaplastic Lymphoma Kinase-Positive (ALK<sup>+</sup>) Non-Small Cell Lung Cancer (ID 12773)

      16:45 - 18:00  |  Author(s): Jean-François Martini

      • Abstract
      • Slides

      Background

      Lorlatinib and crizotinib are oral tyrosine kinase inhibitors with activity against ALK and ROS1 fusion proteins. Crizotinib is well tolerated and has superior efficacy compared to chemotherapy for treatment of patients with advanced ALK+ non-small-cell lung cancer (NSCLC). However, resistance to crizotinib can develop, and the central nervous system (CNS) is often a site of disease relapse. Second-generation ALK inhibitors, ceritinib and alectinib, have demonstrated activity in crizotinib-naive or resistant treatment settings, and alectinib has been shown to have superior progression-free survival (PFS) compared to crizotinib as first-line therapy. Lorlatinib is a selective, CNS-penetrant ALK inhibitor that has potent activity against ALK and kinase domain resistance mutations, including the difficult-to-treat G1202R mutation.Lorlatinib has shown clinical activity in patients previously treated with crizotinib and other ALK inhibitors, including patients with progressive CNS metastases. This study aims to determine if lorlatinib is superior to crizotinib in prolonging PFS in treatment-naïve patients and to identify candidate biomarkers predictive of clinical efficacy or treatment resistance.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Trial Design

      This global, multicenter, open-label phase 3 study will enroll ~280 treatment-naïve patients. Eligible patients must be aged ≥18 years, have Eastern Cooperative Oncology Group performance status of 0–2 and ≥1 measurable extracranial target lesion not previously treated with radiotherapy. Patients with asymptomatic brain metastases are eligible. Patients will be randomized (1:1) to lorlatinib 100 mg once daily or crizotinib 250 mg twice daily and stratified by presence of brain metastases (yes/no) and ethnicity (Asian/non-Asian). Treatment will continue until disease progression, patient refusal, or unacceptable toxicity. Crossover between treatment arms will not be permitted. The primary endpoint is PFS based on blinded independent central review (BICR) using RECIST v1.1. Secondary endpoints include PFS based on investigator assessment, overall survival, objective response (OR) by BICR and investigator assessment; intracranial (IC) OR (periodic magnetic resonance imaging will be performed for central nervous system evaluation), IC time to progression, duration of response and time to response all by BICR; tumor tissue and peripheral blood circulating free DNA biomarker assessment, adverse events and patient-reported health-related outcomes as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 EORTC (QLQ-C30) and EORTC Lung Cancer Module (QLQ-LC13), and the 5-level EuroQol 5-dimension questionnaire (EQ-5D-5L). The first patient was screened on April 14, 2017. This study is registered with ClinicalTrials.gov as NCT03052608.

      4c3880bb027f159e801041b1021e88e8 Result

      Section not applicable

      8eea62084ca7e541d918e823422bd82e Conclusion

      Section not applicable

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