ARIAD announced the start of an international Phase 1/2 clinical trial of brigatinib in September 2011. The initial Phase 1 dose-escalation portion includes patients with advanced solid tumors, particularly those with non-small cell lung cancer (NSCLC). Patients enrolled in this multi-center study are either refractory to available therapies or have no standard treatment available to them. The primary objective of the Phase 1 segment of the Phase 1/2 trial is to determine the initial safety, tolerability, pharmacokinetic profile, recommended dose (anticipated to be once daily) and preliminary anti-tumor activity of brigatinib. The Phase 2 portion of the trial began in June 2013 and includes five expansion cohorts. Enrollment is complete in the Phase 1/2 trial.
In March 2014, ARIAD announced the initiation of its global Phase 2 ALTA trial in patients with locally advanced or metastatic NSCLC who test positive for the ALK oncogene and who were previously treated with crizotinib. This trial was designed to determine the safety and efficacy of brigatinib in treatment of refractory ALK+ NSCLC and enrolled approximately 220 patients, including those with brain metastases. Patients were randomized 1:1 to receive either 90 mg of brigatinib once per day continuously or a lead-in dose of 90 mg per day for seven days followed by 180 mg once per day continuously. The ALTA trial is fully enrolled.
In April 2016, ARIAD announced the initiation of a randomized, first-line Phase 3 ALTA 1L clinical trial of brigatinib in adult patients with ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously been treated with an ALK inhibitor. The trial is designed to assess the efficacy of brigatinib in comparison to crizotinib based on evaluation of the primary endpoint of progression free survival (PFS).
In June 2016, an Expanded Access Study of brigatinib began. The purpose of this Expanded Access Program (EAP) is to provide brigatinib for those patients with locally advanced and/or metastatic patients with ALK+ NSCLC on an expanded access basis due to their inability to meet eligibility criteria for on-going recruiting trials, inability to participate in other clinical trials (e.g., poor performance status, lack of geographic proximity), or because other medical interventions are not considered appropriate or acceptable.