Brigatinib (1 brand name, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- ALUNBRIG
Indications and Usage
ALUNBRIG is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test [see Dosage and Administration (2.1)].
Contraindications
None.
Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of the prescribing information: Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.1)] Hypertension [see Warnings and Precautions (5.2)] Bradycardia [see Warnings and Precautions (5.3)] Visual Disturbance [see Warnings and Precautions (5.4)] Creatine Phosphokinase (CPK) Elevation [see Warnings and Precautions (5.5)] Pancreatic Enzymes Elevation [see Warnings and Precautions (5.6)] Hepatotoxicity [see Warnings and Precautions (5.7)] Hyperglycemia [see Warnings and Precautions (5.8)] Photosensitivity [see Warnings and Precautions (5.9)]
Mechanism of Action
Brigatinib is a tyrosine kinase inhibitor (TKI) with in vitro activity at clinically achievable concentrations against multiple kinases including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R), and FLT-3 as well as EGFR deletion and point mutations. Brigatinib inhibited autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in in vitro and in vivo assays. Brigatinib also inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice. At clinically achievable concentrations (≤500 nM), brigatinib inhibited the in vitro viability of cells expressing EML4-ALK and 17 mutant forms associated with resistance to ALK inhibitors including crizotinib, as well as EGFR-Del (E746-A750), ROS1-L2026M, FLT3-F691L, and FLT3-D835Y. Brigatinib exhibited in vivo antitumor activity against 4 mutant forms of EML4-ALK, including G1202R and L1196M mutants identified in NSCLC tumors in patients who have progressed on crizotinib. Brigatinib also reduced tumor burden and prolonged survival in mice implanted intracranially with an ALK-driven tumor cell line.