Additional Relevant Details
ARIAD’s NDA submission includes clinical data from its Phase 1/2 and pivotal Phase 2 ALTA trials of brigatinib. Data from the ALTA trial, in which patients who had experienced disease progression on crizotinib therapy were randomized to one of two brigatinib regimens, were presented at the 2016 Meeting of the American Society of Clinical Oncology (ASCO). With a median follow-up of 8.3 months, the data show that, for patients treated with the 180 mg regimen with a seven day lead-in at 90 mg (Arm B), 54 percent achieved an investigator-assessed confirmed objective response, the trial’s primary endpoint. In this arm, the median progression free survival (PFS) exceeded one year (12.9 months). Additionally, a 67% confirmed intracranial objective response rate was achieved in patients with measurable brain metastases. The most common treatment-emergent adverse events (TEAEs; ≥ 25% of all patients in Arm B), regardless of relationship to treatment, were nausea (40%), diarrhea (38%), cough (34%), increased blood creatine phosphokinase (30%), headache (27%) and fatigue (27%). TEAEs, ≥ grade 3, occurring in ≥ 5 percent of all patients in Arm B, were increased blood creatine phosphokinase (9%), hypertension (6%) and pneumonia (5%). A subset of pulmonary adverse events with early onset (median: Day 2; range: Day 1-9) occurred in 6 percent of all patients (≥ grade 3 in 3% of patients); no such events with early onset occurred after dose escalation to 180 mg QD in Arm B.