Pembrolizumab

Pembrolizumab
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target PD-1
Clinical data
Pregnancy
category
  • not for pregnant women
Legal status
  • Approved (US)
Routes of
administration		 IV
Identifiers
CAS Number 1374853-91-4
ATC code L01XC18
ChemSpider none
Chemical data
Formula C6504H10004N1716O2036S46 (peptide)
Molar mass 146.3 kDa (peptide)

Pembrolizumab (formerly MK-3475 and lambrolizumab, trade name Keytruda[1]) is a humanized antibody used in cancer immunotherapy. It targets the programmed cell death 1 (PD-1) receptor.[2] The drug was initially used in treating metastatic melanoma.[3][4]

Pembrolizumab was invented by Gregory Carven, Hans van Eenennaam and John Dulos at Organon Biosciences which later became Schering Plough Research Institute and then Merck & Co.[5] MRC Technology humanized the antibody pembrolizumab for Organon in 2006.

On September 4, 2014 the US Food and Drug Administration (FDA) approved pembrolizumab under the FDA Fast Track Development Program.[6] It is approved for use following treatment with ipilimumab, or after treatment with ipilimumab and a BRAF inhibitor in advanced melanoma patients who carry a BRAF mutation.[7] It is marketed by Merck.

On October 2, 2015, the US FDA approved pembrolizumab for the treatment of metastatic non-small cell lung cancer in patients whose tumors express PD-L1 and who have failed treatment with other chemotherapeutic agents.[8][9]

Mechanism of action

Pembrolizumab is a therapeutic antibody that blocks the inhibitory ligand of programmed cell death 1 receptor. This receptor is responsible for inhibiting the immune response against cancer cells. Normally, this effect is necessary to avoid an inappropriate overreaction, such as an auto-immune disease, in healthy individuals.[10] In patients with cancer, antibody blockade against this receptor such as with pembrolizumab reinvigorates the immune system, allowing it to target and destroy cancer cells.[11] Pembrolizumab is one of a number of closely related therapies dubbed immune checkpoint blockade.

Clinical trials

A large phase I trial led to response rates of 37–38% in patients with advanced melanoma and an overall response rate of 26% in patients who had progressive disease after treatment with ipilimumab.[12]

The drug is in Phase II clinical trials for non-small-cell lung cancer (NSCLC) in patients with oligometastatic disease.[13]

See also

External links

References

  1. ↑ "Statement on a Nonproprietary Name Adopted by the USAN Council" (PDF). November 27, 2013.
  2. ↑ Pollack, Andrew (May 29, 2015). "New Class of Drugs Shows More Promise in Treating Cancer I believe this drug was at Sheba Medical Center, the Ella Institute, in Israel.". New York Times. Retrieved May 30, 2015.
  3. ↑ Hamid, O; Robert, C; Daud, A; Hodi, F. S.; Hwu, W. J.; Kefford, R; Wolchok, J. D.; Hersey, P; Joseph, R. W.; Weber, J. S.; Dronca, R; Gangadhar, T. C.; Patnaik, A; Zarour, H; Joshua, A. M.; Gergich, K; Elassaiss-Schaap, J; Algazi, A; Mateus, C; Boasberg, P; Tumeh, P. C.; Chmielowski, B; Ebbinghaus, S. W.; Li, X. N.; Kang, S. P.; Ribas, A (2013). "Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma". New England Journal of Medicine 369 (2): 134–44. doi:10.1056/NEJMoa1305133. PMID 23724846.
  4. ↑ Duek, Nechama (June 9, 2014). "Israeli-American team unveils revolutionary drug in fight against skin cancer". ynetnews.com. Retrieved June 2015.
  5. ↑ US 8952136 Antibodies to human programmed death receptor PD-1
  6. ↑ U.S. Food and Drug Administration (September 4, 2014). "FDA approves Keytruda for advanced melanoma". U.S. Food and Drug Administration. U.S. Food and Drug Administration. Retrieved 24 December 2015.
  7. ↑ "FDA Approves Anti-PD-1 Drug for Advanced Melanoma". cancernetwork.com.
  8. ↑ http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm465444.htm
  9. ↑ U.S. Food and Drug Administration (October 2, 2015). "FDA approves Keytruda for advanced non-small-cell lung cancer". U.S. Food and Drug Administration. U.S. Food and Drug Administration. Retrieved 24 December 2015.
  10. ↑ Francisco LM, Sage PT, Sharpe AH (Jul 2010). "The PD-1 pathway in tolerance and autoimmunity". Immunological Reviews 236: 219–42. doi:10.1111/j.1600-065X.2010.00923.x. PMC 2919275. PMID 20636820.
  11. ↑ Pardoll, DM (Mar 22, 2012). "The blockade of immune checkpoints in cancer immunotherapy.". Nature reviews. Cancer 12 (4): 252–64. doi:10.1038/nrc3239. PMID 22437870.
  12. ↑ Sharma, Pamanee; Allison, James P. (April 3, 2015). "The future of immune checkpoint therapy". Science 348: 56–61. doi:10.1126/science.aaa8172. PMID 25838373. Retrieved June 2015.
  13. ↑ Press release, "Penn Medicine's New Immunotherapy Study Will Pit PD-1 Inhibitor Against Advanced Lung Cancer", University of Pennsylvania, February 4, 2015.


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