brigatinib + lorlatinib + alectinib

A combination regimen of three **small molecule ALK inhibitors**—brigatinib, lorlatinib, and alectinib—used (either sequentially or in specific molecular subgroups) for the targeted treatment of **anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC)**. - **Brigatinib**: second-generation ALK inhibitor with activity against ALK and ROS1 rearrangements; inhibits the tyrosine kinase domain, blocking downstream cell proliferation and survival signals. - **Lorlatinib**: third-generation ALK and ROS1 inhibitor; addresses resistance mutations and provides CNS penetration; inhibits the kinase activity, arresting tumor growth. - **Alectinib**: second-generation ALK inhibitor and highly CNS active; inhibits ALK and RET kinases, blocking proliferation and metastasis. All three agents block ALK signaling at the tyrosine kinase domain, though lorlatinib is most potent against resistance mutations. They are administered orally and are approved for treatment and sequencing in ALK-positive NSCLC patients, especially in cases resistant to first-generation inhibitors or with CNS involvement[1][5][6][7][8].

Brand names

Alunbrig (brigatinib)Lorbrena (lorlatinib)Alecensa (alectinib)

Other names

ALK inhibitors combination