Author of

• 14306

  +

  P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Treatment of Advanced Diseases - NSCLC
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 14392

    +

    P2.01-086 - Ceritinib in ALK+ NSCLC Metastatic to Brain and/or Leptomeninges: The ASCEND-7 Study (ID 290)

    09:30 - 09:30  |  Author(s): P.Y. Wen
    • Abstract

    Background:
    Although the anaplastic lymphoma kinase inhibitor (ALKi), crizotinib achieves high responses in patients with ALK-rearranged (ALK+) non–small cell lung cancer (NSCLC), disease progression within 1 year can occur, with the brain/central nervous system (CNS) as a common site of progression and relapse. Ceritinib is a novel oral ALKi with 20-fold greater potency than crizotinib in enzymatic assays and crosses the blood-brain barrier with good CNS penetration in preclinical studies. In the pivotal phase 1 study (NCT01283516), ceritinib was highly active in ALK+ NSCLC patients (regardless of prior crizotinib exposure) and achieved intracranial responses in 7 of 14 patients with measurable baseline brain lesions. The adverse events profile in these patients was similar to that of the full study population.
    
    Methods:
    This international, prospective, phase 2, open-label study is designed to evaluate the antitumor activity of ceritinib in patients with ALK+ NSCLC metastatic to the brain or leptomeninges (ASCEND-7; CLDK378A2205). Eligible patients must have ALK+ (centrally assessed) NSCLC metastatic to the brain and ≥ 1 extracranial measurable lesion using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients must be neurologically stable ≥ 1 week prior to study drug administration and will be allocated to 1 of 5 arms depending on prior treatment:

    Arms 1-4 (patients with active* brain metastases, without leptomeningeal carcinomatosis [LC])	Prior ALKi treatment	No prior ALKi treatment
    Prior whole brain radiotherapy (WBRT)	Arm 1	Arm 3
    No prior WBRT	Arm 2	Arm 4
    Arm 5: patients with LC with or without evidence of active lesion at baseline

    *Lesion free of local treatment (stereotactic or WBRT) or lesions in unequivocal progression after radiotherapy. Oral ceritinib 750 mg/d will be dosed on a continuous schedule and study assessments are consistent across arms. The primary and key secondary objectives are to evaluate overall response rate and disease control rate, respectively. Other secondary objectives include assessment of intracranial and extracranial responses for all patients and for each of arms 1–4; overall survival and safety for all patients and for each of arms 1–5; and ceritinib pharmacokinetics in all patients. Enrollment is ongoing.
    
    Results:
    This study is in the activation phase.
    
    Conclusion:
    This study will demonstrate the efficacy of ceritinib in ALK+ NSCLC brain metastases and leptomeningeal metastases, in both WBRT-naive patients and prior irradiated patients.