Evaluation of Anaplastic Lymphoma Kinase (ALK) Inhibitor Brigatinib [AP26113] in Patients (PTS) with Alk+ Non–Small Cell Lung Cancer (NSCLC) and Brain Metastases

Abstract

Aim: Central nervous system (CNS) progression has been observed in a substantial proportion of pts treated with crizotinib for ALK+ NSCLC. We report efficacy and safety of brigatinib, an investigational, oral tyrosine kinase inhibitor with preclinical activity against ALK and a broad range of crizotinib-resistant mutants, in ALK+ NSCLC pts with baseline (BL) intracranial CNS metastases. Methods: In this phase 1/2 single-arm, multicenter study (NCT01449461), pts with advanced malignancies received brigatinib 30-300 mg orally once daily. Pts had BL contrast-enhanced MRI of the brain. BL and follow-up brain MRI scans in ALK+ NSCLC pts with intracranial CNS metastases were centrally reviewed by blinded independent neuroradiologists. This post hoc analysis was restricted to intracranial CNS lesions. Measurable lesions were defined as those with longest diameter ≥10 mm; history of local therapy did not inform the analysis. Results: 79 pts with ALK+ NSCLC enrolled in the trial; 46 were identified with brain metastases at BL (42 with prior crizotinib; 4 crizotinib-naive). 38 of the 46 pts were independently evaluated by abstract deadline and included in the efficacy analysis here; updated data will be presented. Median time on study was 51.4 weeks (n = 46). The most common treatment-emergent adverse events in the pts with BL brain metastases were diarrhea, 24 pts (52%); nausea, 24 pts (52%); and fatigue, 23 pts (50%). Conclusions: Brigatinib demonstrated significant intracranial antitumor activity with durable responses in ALK+ NSCLC pts with BL CNS metastases in this study. A prospective evaluation of brigatinib in ALK+ NSCLC pts with brain metastases is under way as part of the phase 2 ALTA study. (Table Presented).