Takeda Pharmaceutical Co. Ltd. announced results from the phase III 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, as assessed by a blinded independent review committee, by more than 50 percent 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.
Findings from the first interim analysis of the ALTA-1L trial was presented during the Presidential Symposium at the International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer in Toronto. 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, 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.
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 percent 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 percent 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, 0.33 to 0.74]; log-rank p=0.0007).
The safety profile associated with ALUNBRIG was generally consistent with the existing U.S. prescribing information.
The phase III ALTA-1L (ALK in Lung Cancer Trial of BrigAtinib 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. Blinded 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 approximately 50 percent of planned PFS events and one at approximately 75 percent of planned PFS events.
