ALK inhibitor

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

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]

EML4-ALK

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

Approved inhibitors

  • crizotinib (Xalkori) (also a ROS1 inhibitor) approved in Aug 2011 by the US FDA for ALK-positive NSCLC.[3]
  • ceritinib (Zykadia), approved by the FDA in April 2014 for treatment of NSCLC.[2][4]
  • alectinib (Alecensa) (Chugai, NDA has been filed in Japan) FDA approved Dec 2015 (accelerated), full approval in 2017 for ALK-positive NSCLC.
  • brigatinib (Alunbrig) (Ariad) (also an EGFR inhibitor) approved in April 2017 by the US FDA for ALK-positive NSCLC.[5]

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)
  • Lorlatinib (PF-06463922, Pfizer)
  • TSR-011 (Tesaro)
  • CEP-37440 (Teva)
  • X-396 (Xcovery)

Discontinued

  • ASP-3026 (Astellas)
  • Dalantercept, ACE-041 (Acceleron)[6]

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.[7] [8]

References

  1. ↑ Nelsen (2010). "ALK Inhibitors: Possible New Treatment for Lung Cancer".
  2. 1 2 Farmer (2010). "Non-Small-Cell Lung Cancer Standards of Care Challenged by a Cornucopia of New Drugs".
  3. ↑ Chustecka (2010). "Crizotinib in ALK-NSCLC; Response Rate "Unprecedented"".
  4. ↑ "FDA Approves Ceritinib for ALK-Positive Lung Cancer". Medscape. April 29, 2014.
  5. ↑ https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm537040.htm
  6. ↑ "Dalantercept". AdisInsight. Retrieved 15 February 2017.
  7. ↑ Galkin; et al. (2007). "Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK".
  8. ↑ "Archived copy". Archived from the original on 2010-12-23. Retrieved 2010-10-02.
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