Phase III ALTA-1L trial of Alunbrig shows benefits in NSCLC +ALK at two years.- Takeda

Takeda Pharmaceutical announced updated data from the Phase III ALTA-1L trial, which evaluated Alunbrig (brigatinib) versus crizotinib in adults with advanced anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) who had not received a prior ALK inhibitor. Results show after more than two years of follow-up, Alunbrig reduced the risk of disease progression or death by 76% (hazard ratio [HR] = 0.24, 95% CI: 0.12�0.45) as assessed by investigators in newly diagnosed patients whose disease had spread to the brain at time of enrollment. Alunbrig also demonstrated a 57% (HR = 0.43, 95% CI: 0.31�0.61) reduction in risk of disease progression or death in all patients. Results from the ALTA-1L trial were evaluated by two separate review bodies � study investigators and a blinded independent review committee (BIRC) � and results from both assessments were reported. At the data cutoff for the second interim analysis (June 28, 2019), the BIRC-assessed HR of progression-free survival (PFS), which is the primary endpoint, was 0.49 (95% CI: 0.35�0.68, log-rank P<0.0001), demonstrating a reduced risk of disease progression or death by 51.>

In addition, Alunbrig demonstrated high and durable responses in the brain, with patients with baseline brain metastases having superior efficacy compared to crizotinib, as assessed by a BIRC, and an early separation of the PFS curves in these patients was observed. Alunbrig reduced the risk of intracranial disease progression or death by 69% in patients with brain metastases at baseline (HR = 0.31, 95% CI: 0.17�0.56), with a median intracranial PFS of 24 months compared to 5.6 months with crizotinib. Median PFS for patients with brain metastases at baseline was not reached with Alunbrig and was 5.9 months with crizotinib, as assessed by investigators. The study confirmed intracranial objective response rate (ORR) for patients with measurable brain metastases at baseline was 78% (95% CI: 52.4�93.6) for patients treated with Alunbrig and 26% (95% CI: 10.2�48.4) for patients treated with crizotinib. Median intracranial duration of response (DOR) in confirmed responders with measurable brain metastases at baseline was not reached (95% CI: 5.7�NE) with Alunbrig and was 9.2 months (95% CI: 3.9�9.2) with crizotinib.

Alunbrig also demonstrated consistent overall efficacy (intent to treat population) with a longer follow-up of 25 months. Median PFS with Alunbrig was 29.4 months (95% CI: 21.2�NE) versus 9.2 months (95% CI: 7.4�12.9) with crizotinib, as assessed by investigators. The BIRC-assessed median PFS was 24.0 months (95% CI: 18.5�NE) for Alunbrig and 11.0 months (95% CI: 9.2�12.9) for crizotinib. Confirmed ORR was 74% (95% CI: 65.5�80.9) for Alunbrig and 62% (95% CI: 52.9�69.7) for crizotinib as assessed by a BIRC. Median DOR was not reached (95% CI: 19.4�NE) with Alunbrig and was 13.8 months (95% CI: 9.3�20.8) with crizotinib as assessed by a BIRC. Quality of life (QoL) for newly diagnosed ALK+ NSCLC patients was also evaluated, with results showing patients treated with Alunbrig experienced significant improvements in health-related QoL (HRQoL). These data will be presented during the Presidential Session at the 2019 European Society for Medical Oncology (ESMO) Asia Congress.