ARIAD Pharmaceuticals, Inc., a rare cancer-focused innovative biotechnology company, has announced clinical data on brigatinib, its investigational anaplastic lymphoma kinase (ALK) inhibitor, from the ongoing Phase 1/2 and pivotal ALTA trials in patients with ALK-positive (ALK+) non-small cell lung cancer (NSCLC) and intracranial central nervous system (CNS) metastases. These data, presented at the International Association for the Study of Lung Cancer (IASLC) 17th World Conference on Lung Cancer (WCLC) Dec. 4-7 in Vienna, showed that in patients with measurable brain metastases, the confirmed intracranial objective response rate (ORR) was 53 percent in the Phase 1/2 trial, and the confirmed intracranial ORR was 67 percent in Arm B (brigatinib 180 mg with seven-day lead-in at 90 mg once daily) in the ALTA trial. Median intracranial progression-free survival (PFS) in ALTA Arm B was 18.4 months.
“Although crizotinib is initially effective in most patients with advanced ALK rearranged lung cancer, patients eventually develop resistance to crizotinib, often with new or progressive brain metastases," said presenting author Scott N. Gettinger, M.D., associate professor of medicine at Yale Cancer Center. “We are clearly encouraged by these data that demonstrate efficacy in the brain, with median intracranial PFS of over one and a half years, in patients with crizotinib refractory disease.”
The ALTA (ALK in Lung Cancer Trial of AP26113) trial enrolled 222 patients with ALK+ NSCLC who had been treated with and experienced disease progression on their most recent crizotinib therapy. Patients were randomized one-to-one to receive either 90 mg of brigatinib once per day (QD) (Arm A), or 180 mg QD with a seven-day lead-in at 90 mg QD (Arm B). In addition, patients were stratified by presence of brain metastases at baseline and best response to prior crizotinib therapy. Patient enrollment is complete, with the last patient enrolled in September 2015. Median follow-up in all patients with intracranial CNS metastases at baseline enrolled in the ALTA trial was 10.7 months as of May 31, 2016.
The Phase 1/2 study of brigatinib included a dose-escalation portion that enrolled patients with advanced solid tumors, particularly those with NSCLC, who were either refractory to available therapies or had no standard treatment available to them. The Phase 2 portion of the trial includes five expansion cohorts. The trial enrolled 137 patients with 79 patients having ALK+ NSCLC. All but eight ALK+ NSCLC patients had failed prior crizotinib therapy. Patient enrollment in the trial is complete, with the last patient enrolled in July 2014. Median follow-up in ALK+ NSCLC patients with intracranial CNS metastases at baseline in the Phase 1/2 study was 24.9 months as of May 31, 2016.
Follow-up Data as of May 31, 2016; Last IRC Data in ALTA Trial was July 13, 2016, and Last Brain Scan in Phase 1/2 Trial was October 8, 2015
The oral presentation, “Brigatinib Activity in Patients with ALK+ NSCLC and Intracranial CNS Metastases in Two Clinical Trials,” (Abstract #4374, Oral ID OA08.06) was presented Dec. 5.Back To Top
Ariad presents updated Brigatinib data at World Conference on Lung Cancer. Appl Rad Oncol.