• Alunbrig achieved a 51% increase in progression free survival compared to crizotinib
• Alunbrig received Breakthrough Therapy Designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib
• Alunbrig has Orphan Drug Designation by the FDA for the treatment of ALK+ NSCLC, ROS1+ and EGFR+ NSCLC.

Takeda Pharmaceutical Company Limited (TSE: 4502) announced on 9/25/18 results from the Phase 3 ALTA-1L (ALK in Lung Cancer Trial of BrigAtinib in 1st Line) trial, demonstrating that ALUNBRIG reduced the risk of disease progression or death, known as progression-free survival (PFS), as assessed by a blinded independent review committee (BIRC), by more than fifty percent compared to crizotinib in adults with anaplastic lymphoma kinase-positive (ALK+) locally advanced or metastatic non-small cell lung cancer (NSCLC) who had not received a prior ALK inhibitor. Findings from the first interim analysis of the ALTA-1L trial will be presented during the Presidential Symposium at the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer (WCLC) in Toronto on Tuesday, September 25, 2018. The data were also simultaneously published online in The New England Journal of Medicine. Alunbrig is currently not approved as first-line therapy for advanced ALK+ NSCLC.

ALTA-1L is a global, 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 but may have received up to one prior regimen of chemotherapy in the advanced setting. Patients were eligible for study entry on the basis of locally determined ALK testing. Patients received either Alunbrig, 180 mg once daily with seven-day lead-in at 90 mg once daily, or crizotinib, 250 mg twice daily. Treatment with Alunbrig resulted in superior PFS compared to crizotinib as assessed by a blinded independent review committee (hazard ratio = 0.49 [95 percent confidence interval (CI), 0.33 to 0.74]; log-rank p=0.0007), corresponding to a 51 percent reduction in the risk of disease progression or death. The safety profile associated with Alunbrig was generally consistent with the existing U.S. prescribing information.

“The ALK+ NSCLC treatment landscape has experienced tremendous change over the last decade, and the ALTA-1L trial demonstrates that brigatinib has the potential to be a key player in the first-line setting,” said D. Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center and the lead investigator of ALTA-1L. “The ALTA-1L trial offers unique aspects, including the real-world applicability of the data. The study’s design offered enrollment to a broader population by allowing patients to participate even if they had received prior chemotherapy and enrolled patients based on local standard of care ALK testing as opposed to mandating confirmation at a central lab. We look forward to further follow-up, which will provide even better understanding of the role of brigatinib in the evolving landscape.”

Key findings, which will be presented by D. Ross Camidge, MD, PhD, Joyce Zeff Chair in Lung Cancer Research at the University of Colorado Cancer Center and lead investigator of ALTA-1L, include:

• A total of 275 patients were randomized to either brigatinib (n=137) or crizotinib (n=138). The median age was 59 years (brigatinib, 58; crizotinib, 60) and 55% of patients in the trial were female (brigatinib, 50%; crizotinib 59%). Twenty-nine percent had brain metastases at baseline (brigatinib, 29%; crizotinib, 30%), with comparable pre-enrollment CNS radiotherapy rates. Overall, 27% of patients had prior chemotherapy in the locally advanced or metastatic setting (brigatinib, 26%; crizotinib, 27%).
• At the data cutoff for the first interim analysis (February 19, 2018), at a median follow-up period of 11.0 and 9.3 months in the brigatinib arm and crizotinib arm, respectively, 95 patients (69%) in the brigatinib arm and 59 patients (43%) in the crizotinib arm remained on study treatment.
• The trial has met the pre-specified threshold for superiority in the primary endpoint at the first interim analysis. With a total of 99 events, BIRC-assessed PFS with brigatinib was superior to crizotinib (hazard ratio, 0.49 [95% confidence interval (CI), 0.33 to 0.74]; log-rank p=0.0007).

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 1.8 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization. Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients. Approximately three to five percent of patients with metastatic NSCLC have a rearrangement in the ALK gene.

Alunbrig is an oral tyrosine kinase inhibitor. It was acquired by Takeda from Ariad in February 2017. In April 2017, Alunbrig received Accelerated Approval from the U.S. Food and Drug Administration (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. In July 2018, Health Canada approved Alunbrig for the treatment of adult patients with ALK+ metastatic NSCLC who have progressed on or who were intolerant to an ALK inhibitor (crizotinib). The FDA and Health Canada approvals of Alunbrig were primarily based on results from the pivotal Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) 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.