Ariad presents updated clinical data on brigatinib in patients with ALK+ NSCLC

ARIAD Pharmaceuticals has announced updated clinical data on its investigational tyrosine kinase inhibitor, brigatinib (AP26113), in patients with anaplastic lymphoma kinase positive (ALK+) advanced non-small cell lung cancer (NSCLC) from an ongoing Phase 1/2 trial. 

The new results include an analysis of safety and efficacy for patients treated at select doses of brigatinib and an evaluation of intracranial central nervous system (CNS) anti-tumour activity.

The updated results were presented at the 2015 European Lung Cancer Conference (ELCC).

The data presented at ELCC focused on the 98 patients treated at doses of 90 mg/day (n=18), 90 mg/day for 1 week followed by escalation to 180 mg/day (n=32), and 180 mg/day (n=48) in the Phase 2 portion of the trial.  All patients receiving these doses were evaluated for safety, and patients with ALK+ NSCLC (n=65) were evaluated for efficacy. 

Brigatinib demonstrated robust anti-tumour activity in patients with crizotinib-resistant ALK+ NSCLC

“The updated data on select doses from the Phase 1/2 trial show robust anti-tumour activity of brigatinib in patients with crizotinib-resistant ALK+ NSCLC, with responses now approaching one year,” stated Rafael Rosell, M.D., Director, Cancer Biology & Precision Medicine Program

Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital in Barcelona, Spain.  “Importantly, by starting at the 90 mg dose, we have seen a reduction of early-onset pulmonary events observed at the higher starting doses.”

The most common adverse events (AEs) of any grade, regardless of treatment relationship, were nausea, diarrhoea, and fatigue. Serious AEs, regardless of treatment relationship, occurring in 4% or more patients, were dyspnea, hypoxia, and pneumonia.

As previously observed and reported, fewer early-onset pulmonary events, including dyspnea, hypoxia, and new pulmonary opacities, were reported with a starting dose of 90 mg vs. 180 mg.  Importantly, no early-onset pulmonary events were observed in the 32 patients started at 90 mg and escalated to 180 mg after 7 days.  

Median progression-free survival (PFS) was 12.9 months for the 90 mg /day cohort, not yet reached for the 90 mg to 180 mg/day cohort, and 11.1 months for the 180 mg/day cohort. 

Phase 1/2 Analysis of CNS Anti-tumour Activity

A separate evaluation of the efficacy and safety of brigatinib in ALK+ NSCLC patients with intracranial CNS metastases at baseline was also presented at the ELCC meeting.  In an independent central radiological review of brain Magnetic Resonance Imaging (MRI) scans, 49 of 79 ALK+ NSCLC patients in the Phase 1/2 trial were identified to have intracranial CNS metastases at baseline.  Of these 49 patients, 16 had measurable intracranial CNS metastases (15 evaluable) and 33 patients had only non-measurable intracranial CNS metastases (30 evaluable).

AEs in patients with CNS metastases occurred at a similar incidence as in the broader study population.

Pivotal Phase 2 ALTA Trial Enrolling Patients

A separate, pivotal global Phase 2 trial of brigatinib (AP26113) in patients with locally advanced or metastatic ALK+ NSCLC who have progressed on crizotinib continues to enroll patients.  The ALTA (ALK in Lung Cancer Trial of AP26113) trial is designed to determine the safety and efficacy of AP26113 in refractory ALK+ NSCLC patients.  The trial will enroll approximately 220 patients including those with brain metastasis.  Patients are randomized 1:1 to receive either 90 mg of brigatinib once per day continuously or a lead-in dose of 90 mg/day for 7 days followed by 180 mg/day continuously.

“We are on track for full patient enrollment in the ALTA trial in the third quarter of this year,” stated Frank G. Haluska, M.D., Ph.D., senior vice president of clinical research and development and chief medical officer at ARIAD.  “We are encouraged by the CNS anti-tumor activity, now exceeding 18 months in the Phase 1/2 brigatinib trial, and look forward to the evaluation of activity on brain metastasis in the ALTA trial.”