BM-32CERITINIB (LDK378) FOR TREATMENT OF PATIENTS WITH ALK-REARRANGED (ALK+) NON-SMALL CELL LUNG CANCER (NSCLC) AND BRAIN METASTASES (BM) IN THE ASCEND-1 TRIAL

BACKGROUND: Ceritinib is an ALK inhibitor (ALKi) recently approved for patients with ALK+ advanced NSCLC. Efficacy and safety were evaluated in a subset of patients with BM in the phase I ASCEND-1 study. In 246 patients with ALK+ NSCLC who received ceritinib 750 mg/day, overall response rate (ORR) was 58.5% (95% CI: 52.1, 64.8) and was 66.3% (55.1, 76.3) and 54.6% (46.6, 62.4) in ALKi-naive and ALKi-treated patients, respectively. METHODS: Patients with ALK+ advanced NSCLC and clinically/neurologically stable BM at baseline who received ceritinib 750 mg/day were analyzed for response based on investigator assessment. RESULTS: Among 246 patients, 124 had BM at baseline, including 98 with prior ALKi treatment and 26 who were ALKi-naive. The BM subset had a median age of 51.0 years; 85.5% with an ECOG PS ≤1; 58.1% Caucasian, 39.5% Asian; median time from NSCLC diagnosis to first ceritinib dose was 20.5 months. Median duration of exposure was 27 weeks. ORR was 54.0% (44.9, 63.0) in the full cohort [50.0% (39.7, 60.3) in ALKi-treated and 69.2% (48.2, 85.7) in ALKi-naive]. Median DOR was 7.0 mo (5.5, 9.7) for the full subset [6.9 mo (4.8, 8.5) in ALKi-treated and not estimable (NE) in ALKi-naive]. Median PFS was 6.9 mo (5.4, 8.4) [6.7 mo (4.9, 8.4) and 8.3 mo (4.6, NE) in ALKi-treated and ALKi-naive]. Measurable target lesions were identified at baseline in 14 patients (10 ALKi-treated, 4 ALKi-naive). Seven of these patients achieved a response in the brain (4 ALKi-treated, 3 ALKi-naive) and 3 had stable disease (all ALKi-treated). The most common adverse events (all grades) in all patients and the BM subset were diarrhea (86% vs 79%), nausea (80% vs 82%), and vomiting (60% vs 63%). CONCLUSIONS: Ceritinib has clinically significant durable efficacy in patients with ALK+ NSCLC, including patients with BM, regardless of prior ALKi treatment.