ALK inhibitor

ALK inhibitors are potential anti-cancer drugs that act on tumours with variations of anaplastic lymphoma kinase (ALK) such as an EML4-ALK translocation.[1]

Micrograph showing an ALK positive adenocarcinoma of the lung. The ALK immunostain allows individuals with ALK rearrangements to be identified.

EML4-ALK

About 4-7% of non-small cell lung carcinomas (NSCLC) have EML4-ALK translocations.[2]

Approved inhibitors

  • crizotinib (also a ROS1 inhibitor) approved in Aug 2011 by the US FDA for ALK-positive NSCLC.[3]
  • ceritinib, approved by the FDA in April 2014 for treatment of NSCLC.[2][4]
  • alectinib FDA approved Dec 2015 (accelerated), full approval in 2017 for ALK-positive NSCLC.
  • brigatinib (also an EGFR inhibitor) approved in April 2017 by the US FDA for ALK-positive NSCLC.[5]
  • lorlatinib approved in 2018 by the US FDA for ALK-positive NSCLC.

Clinical trials

Additional ALK inhibitors currently (or soon to be) undergoing clinical trials include:

  • Entrectinib (Nerviano's NMS-E628, licensed by Ignyta and renamed RXDX-101, in the U.S. orphan drug designation and rare pediatric disease designation for the treatment of neuroblastoma and orphan drug designation for treatment of TrkA-, TrkB-, TrkC-, ROS1- and ALK-positive NSCLC)
  • TSR-011 (Tesaro)
  • CEP-37440 (Teva)
  • X-396 (Xcovery)

Discontinued

  • ASP-3026 (Astellas)


NPM-ALK

NPM-ALK is a different variation/fusion of ALK that drives anaplastic large-cell lymphomas (ALCLs) and is the target of other ALK inhibitors.[6] [7]

References

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