390OEfficacy and safety of ceritinib in ALK-positive non-small cell lung cancer (NSCLC) patients with leptomeningeal metastases (LM): Results from the phase II, ASCEND-7 study

Abstract Background LM are seen in approximately 5% of ALK+ NSCLC patients (pts), and are associated with poor prognosis with standard treatment. Ceritinib is highly active in ALK+ NSCLC pts with previously reported intracranial/central nervous system activity. We report the efficacy and safety of ceritinib in ALK+ NSCLC pts with LM enrolled in the ASCEND-7 study (NCT02336451). Methods Pts with documented ALK + (FISH) NSCLC, CSF invasiveness with radiologically or cytologically confirmed LM, and ≥1 extracranial measurable lesion using RECIST v1.1 were eligible. The study objectives included evaluation of antitumor activity based on overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Data cut-off was Feb 6, 2019. Results Of the 18 LM pts enrolled, 14 pts (77.8%) also had brain metastases and 8 pts (44.4%) had measurable brain metastases at baseline. Majority of the pts (n = 16, 88.9%) had received prior crizotinib and 7 pts (38.9%) had received prior brain radiotherapy. Median duration of exposure to ceritinib was 18.1 weeks (range: 1.7–125.9). Whole body ORR by investigator assessment was 16.7% (95% CI: 3.6, 41.4) with median duration of response of 5.5 months (95% CI: 3.7, 9.9) and a clinically significant median PFS of 5.2 months (95% CI: 1.6, 7.2). Median duration of follow-up for PFS was 3.84 months (range: 0.5–13). Additional efficacy endpoints are included in the below Table. Adverse events (AEs, all grades, regardless of study drug relationship) were reported in all 18 pts. Grade 3/4 AEs occurring in ≥ 10% of pts were increased alanine aminotransferase (22.2%), hyperglycemia (16.7%), increased gammaglutamyltransferase (11.1%), pneumonia (11.1%), and increased lipase (11.1%). Table: Efficacy results Table: 390OEndpoint per investigator assessmentArm 5 (ALK+ NSCLC pts with LM) N = 18Whole body Response (RECIST v1.1)ORR, % (95% CI)16.7 (3.6, 41.4)DCR, % (95% CI)66.7 (41.0, 86.7)Median DOR, (months) [95% CI]5.5 (3.7, 9.9)Median PFS, (months) [95% CI]5.2 (1.6, 7.2)Intracranial response* (modified RECIST v1.1)M = 8ORR, % (95% CI)12.5 (0.3, 52.7)DCR, % (95% CI)62.5 (24.5, 91.5)Extracranial response (RECIST v1.1)ORR, % (95% CI)22.2 (6.4, 47.6)DCR, % (95% CI)72.2 (46.5, 90.3)Median OS, months (95% CI)7.2 (1.6, 16.9)*In patients with measurable brain metastases M, number of patients with measurable brain metastases at baseline DCR, disease control rate; DOR, duration of response; NE, not estimable; ORR, overall respon