The global, randomized, phase III ALTA-1L trial met its primary endpoint at the first pre-specified interim analysis, with Alunbrig (brigatinib) demonstrating a statistically significant improvement in progression-free survival compared to crizotinib in adults with anaplastic lymphoma kinase-positive locally advanced or metastatic non-small cell lung cancer who had not received a prior ALK inhibitor.
Takeda Pharmaceutical Company Limited sponsors this drug.
The trial was designed to assess the efficacy and safety of ALUNBRIG in comparison to crizotinib based on evaluation of the primary endpoint of PFS, or length of time from the start of treatment that a patient lives without the disease getting worse. Alunbrig is currently not approved as frontline therapy.
The safety profile associated with Alunbrig from the ALTA-1L (ALK in Lung Cancer Trial of AP26113 in 1st Line) trial was generally consistent with the existing prescribing information, with no new safety concerns.
The results from this interim analysis will be submitted for presentation at an upcoming medical meeting.
The phase III ALTA-1L (ALK in Lung Cancer Trial of AP26113 in 1st Line) trial of Alunbrig in adults is a global, ongoing, randomized, open-label, comparative, multicenter trial, which enrolled 275 patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor.
Patients received either Alunbrig, 180 mg once daily with seven-day lead-in at 90 mg once daily, or crizotinib, 250 mg twice daily. Independent Review Committee-assessed progression-free survival was the primary endpoint.
Secondary endpoints included objective response rate per RECIST v1.1, intracranial ORR, intracranial PFS, overall survival, safety and tolerability. A total of approximately 198 PFS events are planned at the final analysis of the primary endpoint in order to demonstrate a minimum of six months PFS improvement over crizotinib.
The trial is designed with two pre-specified interim analyses for the primary endpoint—one at 50 percent of planned PFS events and one at 75 percent of planned PFS events.
Alunbrig is a targeted cancer medicine discovered by Ariad Pharmaceuticals Inc., which was acquired by Takeda in February 2017. In April 2017, Alunbrig received Accelerated Approval from the FDA for ALK+ metastatic NSCLC patients who have progressed on or are intolerant to crizotinib.
This indication is approved under Accelerated Approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Alunbrig received Breakthrough Therapy Designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib and was granted Orphan Drug Designation by the FDA for the treatment of ALK+ NSCLC, ROS1+ and EGFR+ NSCLC.
A Marketing Authorization Application for Alunbrig was submitted to the European Medicines Agency in Feb 2017.
The brigatinib clinical development program further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with ALK+ NSCLC worldwide and the healthcare professionals who treat them.
The comprehensive program includes the following clinical trials:
Phase I/II trial, which was designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of Alunbrig.
Pivotal phase II ALTA trial investigating the efficacy and safety of Alunbrig at two dosing regimens in patients with ALK+ locally advanced or metastatic NSCLC who had progressed on crizotinib
Phase IIII ALTA-1L trial assessing the efficacy and safety of Alunbrig in comparison to crizotinib in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor
Phase II single-arm, multicenter study in Japanese patients with ALK+ NSCLC, focusing on patients who have progressed on alectinib
Phase II global study evaluating Alunbrig in patients with advanced ALK+ NSCLC who have progressed on alectinib or ceritinib
