The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of brigatinib (Alunbrig) as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor.
Brigatinib is a next-generation tyrosine kinase inhibitor (TKI) that was designed to target and inhibit ALK genetic alterations.
The drug is being evaluated in phase 3 ALTA-1L trial in comparison with crizotinib in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor.
Results from the trial showed brigatinib demonstrated superiority compared to crizotinib with significant responses observed in patients with baseline brain metastases.
After more than two years of follow-up, brigatinib reduced the risk of intracranial disease progression or death by 69% in patients with brain metastases at baseline (hazard ratio [HR] = 0.31, 95% CI: 0.17–0.56), as assessed by a blinded independent review committee (BIRC), and reduced the risk of disease progression or death by 76% in patients with brain metastases at baseline (HR = 0.24, 95% CI: 0.12–0.45), as assessed by investigators.
It also demonstrated consistent overall efficacy, with a median progression-free survival (PFS) more than two times longer than that with crizotinib at 24.0 months (95% CI: 18.5–NE) versus 11.0 months (95% CI: 9.2–12.9) for crizotinib, as assessed by BIRC, and 29.4 months (95% CI: 21.2–NE) versus 9.2 months (95% CI: 7.4–12.9), as assessed by investigators.
The safety profile of brigatinib in the ALTA-1L trial was generally consistent with the existing European summary of product characteristics (SmPC).
The most common treatment-emergent adverse events (TEAEs) Grade =3 in the brigatinib arm were increased CPK (24.3%), increased lipase (14.0%) and hypertension (11.8%); and for crizotinib were increased ALT (10.2%), increased AST (6.6%), and increased lipase (6.6%).
Brigatinib is currently approved in more than 40 countries, including the US, Canada and the European Union, for the treatment of people living with ALK+ metastatic NSCLC who have taken the medicine crizotinib, but their NSCLC has worsened or they cannot tolerate taking crizotinib, Takeda said.
The drug received Breakthrough Therapy Designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumours are resistant to crizotinib and was granted Orphan Drug Designation by the FDA for the treatment of ALK+ NSCLC, ROS1+ and EGFR+ NSCLC.