Brigatinib in ALK+ NSCLC pts with intracranial CNS metastases in 2 clinical trials

Abstract

Background: The investigational next-generation anaplastic lymphoma kinase (ALK) inhibitor brigatinib is being evaluated in patients (pts) with ALK-positive non-small cell lung cancer (ALK+NSCLC) in a phase 1/2 trial (Ph1/2) and a pivotal phase 2 trial (ALTA);most of these pts had intracranial central nervous system (CNS) metastases at baseline. Methods: In Ph1/2 (NCT01449461), pts with advanced malignancies, including ALK+ NSCLC, received brigatinib (30-300 mg/d). In ALTA (NCT02094573), crizotinibresistant pts with advanced ALK+NSCLC received brigatinib at 90 mg qd in arm A or 180 mg qd with a 7-day lead-in at 90 mg in arm B. ALK+NSCLC pts with baseline brain metastases were analyzed. CNS efficacy in both trials and safety in ALTA are shown. Results: In Ph1/2 and ALTA, 50/79 (63%) and 154/222 (69%) ALK+NSCLC pts had baseline brain metastases based on independent review committee (IRC) and investigator assessment, respectively. Most pts had received chemotherapy (Table). In Ph1/2 25/50 (50%) pts were receiving brigatinib as of 16 November 2015; in ALTA, 101/154 (66%) pts were receiving brigatinib as of 29 February 2016. In pts with measurable brain lesions, confirmed intracranial objective response rate was 53% in Ph1/2 and 42%/67% in ALTA A/B (Table). In pts with only nonmeasurable brain lesions, 35% (11/31) in Ph1/2 and 7% (4/54)/18% (10/55) in ALTA A/B had confirmed complete resolution of brain lesions. Further data are shown in the table. The most common treatment-emergent adverse events (TEAEs) in the 151 treated ALTA pts with baseline brain metastases were nausea (A/B, 32%/43%), headache (30%/30%), diarrhea (18%/36%), cough (21%/30%), and vomiting (25%/26%); the most common grade 3 TEAEs were increased blood creatine phosphokinase (1%/11%), hypertension (4%/7%), increased lipase (3%/3%), and pneumonia (1%/4%). Conclusions: Brigatinib yielded substantial clinical activity in ALK+ NSCLC pts with brain metastases in 2 trials.