Previous report from the ASCEND-8 (NCT02299505) trial showed consistent efficacy of ceritinib 450 mg-fed vs 750 mg-fasted with less gastrointestinal (GI) toxicity in pts with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic NSCLC (Cho BC, et al 2019 JTO). Here, we report results from Asian pts in the ASCEND-8 trial.
Key efficacy endpoints were blinded independent review committee (BIRC)-assessed overall response rate (ORR) and duration of response (DOR) evaluated per RECIST v1.1. Other endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate (DCR); overall survival (OS) and safety per CTCAE v4.03.
As of the final data cut-off date (March 6, 2020), 198 treatment-naïve pts were included in the efficacy analysis, of which 74 (37% of the full analysis set) comprised the Asian subset; 450 mg-fed (n=29), 600 mg-fed (n=19) and 750 mg-fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more pts in the 450 mg-fed arm had brain metastasis vs 750 mg-fasted arm (44.8% vs 26.9%). Efficacy results in Asian pts are shown in the table. Per BIRC, pts in the 450 mg-fed arm had numerically higher ORR, median DOR, 24-month DOR rate, median PFS, and 24-month PFS rate vs 750 mg-fasted arm, with overlapping confidence intervals (CI). The 36-month OS rate was 93.1% in the 450 mg-fed arm vs 70.9% in the 750-mg fasted arm. Any grade GI toxicity (group event for nausea, diarrhea and vomiting) occurred in 82.8%, 78.9% and 96.2% pts in 450 mg-fed, 600 mg-fed and 750 mg-fasted arms, respectively. Grade 3/4 GI toxicity occurred in 1 (3.4%) patient in the 450 mg-fed arm, 1 (5.3%) patient in the 600 mg-fed arm and 2 (7.7%) pts in the 750 mg-fasted arm. Table: 1348P
|Efficacy per BIRC||450 mg-fed (N=29)||600 mg-fed (N=19)||750 mg-fasted (N=26)|
|ORR, % (95% CI)||82.8 (64.2, 94.2)||78.9 (54.4, 93.9)||76.9 (56.4, 91.0)|
|DCR, % (95% CI)||96.6 (82.2, 99.9)||89.5 (66.9, 98.7)||88.5 (69.8, 97.6)|
|Median DOR (95% CI), months [n/Ne]||NE (16.4, NE) [7/24]||20.7 (4.2, NE) [8/15]||13.2 (4.5, 17.9) [15/20]|
|DOR rate at 24 months, % (95% CI)||68.2 (44.5, 83.4)||44.9 (16.4, 70.1)||20.3 (5.5, 41.5)|
|Median PFS (95% CI), months||NE (16.9, NE)||21.9 (4.1, NE)||8.2 (5.4, 16.6)|
|PFS rate at 24 months, % (95% CI)||58.9 (37.9, 74.9)||37.6 (14.0, 61.5)||22.0 (8.4, 39.5)|
|OS rate at 36 months, % (95% CI)||93.1 (75.1, 98.2)||62.4 (28.5, 83.7)||70.9 (47.9, 85.1)|
n/Ne: number of events/number of confirmed responders. NE, non-estimable.
Asian pts with ALK+ advanced/metastatic NSCLC treated with ceritinib 450 mg-fed showed numerically higher efficacy and less GI toxicity compared to 750 mg-fasted pts.
Clinical trial identification
We thank Dr. Varunkumar Pandey, PhD of Novartis Healthcare Pvt. Ltd for providing medical editorial assistance with this abstract.
Legal entity responsible for the study
B.C. Chul Cho: Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Novartis, Bayer, AstraZeneca, MOGAM Institute, Pfizer, Dong-A ST, Eli Lilly, Champions Oncology, Janssen, Yuhan, Ono, Dizal Oharma, Merck Sharp & Dohme, Roche, Bristol-Myers Squibb, Takeda; Shareholder/Stockholder/Stock options: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics; Honoraria (self): Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, Merck Sharp & Dohme; Research grant/Funding (self): Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, Merck Sharp & Dohme; Licensing/Royalties: Champions Oncology. D-W. Kim: Travel/Accommodation/Expenses: Amgen, Daiichi Sankyo; Research grant/Funding (institution): Alpha Biopharma, AstraZeneca / MedImmune, Boehringer Ingelheim, Hanmi, Janssen, Merus, Mirati Therapeutics, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan. K. Park: Speaker Bureau/Expert testimony: AstraZeneca, Amgen, Blueprint, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Hanmi, Incyte, Janssen, Loxo, Merck KGaA, Merck Sharp & Dohme, ONO, Roche; Advisory/Consultancy: Novartis. S-W. Kim: Advisory/Consultancy: Novartis, Boehringer Ingelheim, Lilly, AstraZeneca; Speaker Bureau/Expert testimony: Boehringer Ingelheim; Research grant/Funding (self): AstraZeneca, Novartis. V. Sriuranpong: Speaker Bureau/Expert testimony: AstraZeneca, Novartis, Eisai, Boehringer Ingelheim, Taiho, Merck Sharp & Dohme, Bristol-Myers Squibb, Amgen; Advisory/Consultancy: Eisai, Merck Sharp & Dohme, Amgen, Roche; Research grant/Funding (self): AstraZeneca, Novartis, Merck Sharp & Dohme, Pfizer, Roche. K. Amin, L. Wang, M. Bhering: Full/Part-time employment: Novartis. Y. Wang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Novartis. S. Lucien Geater: Honoraria (self): AstraZeneca, Boehringer Ingelheim; Advisory/Consultancy: Boehringer Ingelheim; Research grant/Funding (self): AstraZeneca, Boehringer Ingelheim, Novartis, Roche. All other authors have declared no conflicts of interest.