Lorlatinib (LORBRENA, Pfizer) is the fifth ALK TKI to enter the US market. As a 3rd generation TKI, lorlatinib was designed to target a broader spectrum of ALK mutations, including those associated with acquired resistance to 2nd generation TKIs. A pivotal phase 1/2 study resulted in FDA Breakthrough Designation in 2017, and accelerated approval in 2018, for ALKpos NSCLC progressing on one or more prior ALK TKIs. .
CROWN is one of four phase 3 studies comparing a next generation ALK TKI to crizotinib. So far, the 2nd generation ALK TKIs show very similar PFS benefits vs crizotinib in tx-naïve pts (HR: 0.5). To stand out, the CROWN study would need to show an HR of 0.45 or less.
No further Pfizer-sponsored studies are ongoing.
Reference
CROWN: NCT03052608
