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P3.02a-036 Phase 1 Study of Ceritinib 450 mg or 600 mg Taken with a Low-Fat Meal versus 750 mg in Fasted State in ALK+ Metastatic NSCLC
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54 patients (94.7%) and the median survival after stenting was 3.7 months. At death, only 8 (14%) of those patients died due to direct airway symptoms, including respiration difficulty, even when their general condition was good (Suffocation death group). Conversely, the other 49 patients mostly died due to systemic cancer spread, but all 49 cases had no pain associated with airway symptoms. Therefore, suffocation death appears to have been avoided in those 49 (85.9%) patients (Nonsuffocation death group). In a univariate analysis, “Stent migration,” “Tracheal stenosis,” and “Thyroid cancer” were potentially significant factors regarding suffocation death. In a multivariate analysis, “Stenosis at mid trachea” was found to be an independent predictive factor for suffocation death (p ¼ 0.02). Conclusion: Suffocation death can be effectively prevented by the use of airway stenting treatment. “Stenosis at mid trachea” is the most problematic factor when attempting to obtain some benefit from stenting and this may be due to the difficulty of achieving accurate stent (mainly straight silicon stent) fixation in such lesions. Keywords: suffocation, airway stent
P3.02a-036 Phase 1 Study of Ceritinib 450 mg or 600 mg Taken with a Low-Fat Meal versus 750 mg in Fasted State in ALK+ Metastatic NSCLC Topic: Miscellaneous Rafal Dziadziuszko,1 Dong-Wan Kim,2 Alessandra Bearz,3 Scott Laurie,4 Mark Mckeage,5 Keunchil Park,6 Sang-We Kim,7 Vanessa Q. Passos,8 Karen Osborne,9 Yvonne Y. Lau,10 Jessie Gu,10 Byoung Chul Cho11 1Oncology and Radiotherapy, Medical University of Gdansk, Gdansk/Poland, 2Seoul National University Hospital, Seoul/Korea, Republic of, 3 Centro Di Riferimento Oncologico-Ircc, Aviano/Italy, 4 Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa/Canada, 5University of Auckland, Auckland/New Zealand, 6Div of HEM/ONC, Samsung Med Ctr, Sungkyunkwan Univ School of Med, Seoul/Korea, Republic of, 7Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/Korea, Republic of, 8Novartis Pharmaceutical Corporation, East Hanover/NJ/United States of America, 9 Novartis Pharma Ag, Basel/Switzerland, 10Novartis Pharmaceutical Corporation, East Hanover/United States of America, 11Medical Oncology, Yonsei Cancer Center, Seoul/Korea, Republic of
Journal of Thoracic Oncology
Vol. 12 No. 1S
Background: The anaplastic lymphoma kinase (ALK) inhibitor ceritinib is approved at 750 mg fasted for the treatment of patients with ALK-rearranged (ALK+) metastatic non-small cell lung cancer (NSCLC) pretreated with crizotinib. The pharmacokinetic (PK) part of this study (Part 1) compares PK exposure of ceritinib following food consumption versus a fasted state in advanced ALK+ NSCLC patients. Methods: Part 1 of this prospective, open-label, multicenter, randomized, 3-arm, phase 1 study (ASCEND-8; NCT02299505) is investigating PK and safety of ceritinib in advanced ALK+ NSCLC patients, treatment-naïve or pretreated with multiple lines of chemotherapy and/or crizotinib. Here, we compare steady-state PK of ceritinib 450 or 600 mg taken with a low-fat meal versus ceritinib 750 mg fasted (primary endpoint) and report preliminary safety outcomes from Part 1. Part 2 continues to randomize treatment-naïve patients and will assess safety and efficacy. Results: As of June 16, 2016 (data cut-off), 137 patients were randomized in a 1:1:1 ratio to each treatment arm; 135 patients received one dose (safety set) and 97 patients had evaluable steady-state PK data. Disease characteristics were comparable between arms. Median follow-up duration was 4.14 months (range, 0.1e13.9). Relative to 750 mg fasted, the 450 mg fed arm demonstrated comparable steady-state PK, while the 600 mg fed arm showed w25% higher steady-state PK (Table). Preliminary safety data suggests overall frequency of AEs and types of AEs were comparable between arms. However, incidences of gastrointestinal (GI)-related AEs (diarrhea, nausea or vomiting) were lowest, with no grade 3/4 GI AEs reported, in the 450 mg fed arm.
Conclusion: Steady-state PK was comparable in advanced ALK+ NSCLC patients taking ceritinib 450 mg with a low-fat meal versus 750 mg fasted. This study continues to enroll treatment-naïve patients into Part 2 to assess efficacy across the three treatment arms and assess longer safety follow-up. Keywords: Ceritinib, ALK, NSCLC
54 patients (94.7%) and the median survival after stenting was 3.7 months. At death, only 8 (14%) of those patients died due to direct airway symptoms, including respiration difficulty, even when their general condition was good (Suffocation death group). Conversely, the other 49 patients mostly died due to systemic cancer spread, but all 49 cases had no pain associated with airway symptoms. Therefore, suffocation death appears to have been avoided in those 49 (85.9%) patients (Nonsuffocation death group). In a univariate analysis, “Stent migration,” “Tracheal stenosis,” and “Thyroid cancer” were potentially significant factors regarding suffocation death. In a multivariate analysis, “Stenosis at mid trachea” was found to be an independent predictive factor for suffocation death (p ¼ 0.02). Conclusion: Suffocation death can be effectively prevented by the use of airway stenting treatment. “Stenosis at mid trachea” is the most problematic factor when attempting to obtain some benefit from stenting and this may be due to the difficulty of achieving accurate stent (mainly straight silicon stent) fixation in such lesions. Keywords: suffocation, airway stent
P3.02a-036 Phase 1 Study of Ceritinib 450 mg or 600 mg Taken with a Low-Fat Meal versus 750 mg in Fasted State in ALK+ Metastatic NSCLC Topic: Miscellaneous Rafal Dziadziuszko,1 Dong-Wan Kim,2 Alessandra Bearz,3 Scott Laurie,4 Mark Mckeage,5 Keunchil Park,6 Sang-We Kim,7 Vanessa Q. Passos,8 Karen Osborne,9 Yvonne Y. Lau,10 Jessie Gu,10 Byoung Chul Cho11 1Oncology and Radiotherapy, Medical University of Gdansk, Gdansk/Poland, 2Seoul National University Hospital, Seoul/Korea, Republic of, 3 Centro Di Riferimento Oncologico-Ircc, Aviano/Italy, 4 Medical Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa/Canada, 5University of Auckland, Auckland/New Zealand, 6Div of HEM/ONC, Samsung Med Ctr, Sungkyunkwan Univ School of Med, Seoul/Korea, Republic of, 7Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/Korea, Republic of, 8Novartis Pharmaceutical Corporation, East Hanover/NJ/United States of America, 9 Novartis Pharma Ag, Basel/Switzerland, 10Novartis Pharmaceutical Corporation, East Hanover/United States of America, 11Medical Oncology, Yonsei Cancer Center, Seoul/Korea, Republic of
Journal of Thoracic Oncology
Vol. 12 No. 1S
Background: The anaplastic lymphoma kinase (ALK) inhibitor ceritinib is approved at 750 mg fasted for the treatment of patients with ALK-rearranged (ALK+) metastatic non-small cell lung cancer (NSCLC) pretreated with crizotinib. The pharmacokinetic (PK) part of this study (Part 1) compares PK exposure of ceritinib following food consumption versus a fasted state in advanced ALK+ NSCLC patients. Methods: Part 1 of this prospective, open-label, multicenter, randomized, 3-arm, phase 1 study (ASCEND-8; NCT02299505) is investigating PK and safety of ceritinib in advanced ALK+ NSCLC patients, treatment-naïve or pretreated with multiple lines of chemotherapy and/or crizotinib. Here, we compare steady-state PK of ceritinib 450 or 600 mg taken with a low-fat meal versus ceritinib 750 mg fasted (primary endpoint) and report preliminary safety outcomes from Part 1. Part 2 continues to randomize treatment-naïve patients and will assess safety and efficacy. Results: As of June 16, 2016 (data cut-off), 137 patients were randomized in a 1:1:1 ratio to each treatment arm; 135 patients received one dose (safety set) and 97 patients had evaluable steady-state PK data. Disease characteristics were comparable between arms. Median follow-up duration was 4.14 months (range, 0.1e13.9). Relative to 750 mg fasted, the 450 mg fed arm demonstrated comparable steady-state PK, while the 600 mg fed arm showed w25% higher steady-state PK (Table). Preliminary safety data suggests overall frequency of AEs and types of AEs were comparable between arms. However, incidences of gastrointestinal (GI)-related AEs (diarrhea, nausea or vomiting) were lowest, with no grade 3/4 GI AEs reported, in the 450 mg fed arm.
Conclusion: Steady-state PK was comparable in advanced ALK+ NSCLC patients taking ceritinib 450 mg with a low-fat meal versus 750 mg fasted. This study continues to enroll treatment-naïve patients into Part 2 to assess efficacy across the three treatment arms and assess longer safety follow-up. Keywords: Ceritinib, ALK, NSCLC