Drugs slow disease progression and improve response rates in patients previously treated with crizotinib.
Data from a Phase III study evaluating Novartis’ selective anaplastic lymphoma kinase (ALK) gene inhibitor, Zykadia® (ceritinib), showed that first-line treatment with the drug resulted in a 45% reduction in the risk of disease progression in patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC). The firm said in a statement that it is now in discussions with regulatory authorities with respect to the potential use of the drug to improve outcomes for patients with ALK+ advanced NSCLC.
Results from the open-label, active-controlled Ascend-4 study found that patients treated using first-line Zykadia had a median progression-free survival (PFS) of 16.6 months, compared with 8.1 months for patients treated using chemotherapy with maintenance.
Additional data from Ascend-4 showed that patients taking Zykadia had an overall response rate (ORR) of 72.5%, compared with 26.7% for patients treated using standard chemotherapy. For patients with measurable brain metastases the overall intracranial response rate was 72.7% with Zykadia, compared with 27.3% for patients treated using standard chemotherapy. Patients without brain metastases experienced a median progression-free survival of 26.3 months with Zykadia compared with 8.3 months for standard chemotherapy. A disease control rate of 84.7% and duration of response rate of 23.9 months were achieved among Zykadia-treated patients.
Novartis says the trial has yet to reach the point where it can collect overall survival data, which is a key secondary endpoint, although the data do indicate a positive trend in favor of first line Zykadia, even though 72.4% of patients in the chemotherapy arm also received an ALK inhibitor as a first treatment after chemotherapy. The Ascend-4 study results were presented at the 17th World Conference on Lung Cancer, hosted by the International Association for the Study of Lung Cancer, in Vienna.
In the U.S., Zykadia was granted accelerated approval in 2014 as a treatment for patients with ALK-positive metastatic NSCLC who have progressed during treatment with, or are intolerant to crizotinib. Approval for Zykadia in Europe was granted in 2015 for the use of Zykadia to treat adult patients with ALK+ advanced NSCLC previously treated with crizotinib.
The Zykadia trial data were released the day after Ariad Pharmaceuticals reported positive data from both a Phase I/II study and a pivotal trial evaluating its ALK inhibitor, brigatinib, in patients with ALK+ NSCLC and intracranial central nervous system metastases. Patients in the pivotal ALTA trial had been treated with and experienced disease progression on their most recent crizotinib therapy. Patients in the Phase I/II study were either refractory to available therapies or had no standard treatments available to them. The Ariad study data, also presented at WCLC in Vienna, showed that in patients with measurable brain metastases, the confirmed intracranial objective response rate (ORR) was 53% in the Phase I/II trial, and the confirmed intracranial ORR was 67% in Arm B (brigatinib 180 mg with seven-day lead-in at 90 mg once daily) in the ALTA trial. Median intracranial PFS in ALTA Arm B was 18.4 months.
Ariad has initiated the Phase III ALTA 1L trial to assess the efficacy and safety of brigatinib in comparison to crizotinib in patients with locally advanced or metastatic ALK+ NSCLC who have not received prior treatment with an ALK inhibitor.