Pembrolizumab

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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 (WHO)
PubChem SID: 254741536
DrugBank DB09037
UNII DPT0O3T46P
Chemical data
Formula C6534H10004N1716O2036S46 (peptide)
Molecular mass 146.3 kg/mol (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]

History

Pembrolizumab was invented by Gregory Carven, Hans van Eenennaam and John Dulos at Organon Biosciences.[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 FDA approved pembrolizumab for the treatment of metastatic non-small cell lung cancer (NSCLC) in patients whose tumors express PD-L1 and who have failed treatment with other chemotherapeutic agents.[8][9]

Pembrolizumab was priced at $150,000 per year when it launched.[10]

Mechanism of action

Pembrolizumab is a therapeutic antibody that blocks the inhibitory ligand of programmed cell death 1 receptor located on lymphocytes. This receptor is responsible for inhibiting the immune response to cancer cells which express programmed death-ligand (PD-L1 or PD-L2). Normally, this effect is necessary to avoid inappropriate overreaction, such as an auto-immune disease, in healthy individuals.[11] In cancer patients antibody blockade against this receptor such as with Pembrolizumab reinvigorates the immune system, allowing it to target and destroy cancer cells.[12] Pembrolizumab is one of a number of closely related therapies dubbed checkpoint therapy.

Clinical trials

As of 2015 a large phase I clinical trial produced 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.[13]

Also in 2015 the drug was in Phase II clinical trials for non-small-cell lung cancer (NSCLC) in patients with oligometastatic disease.[14]

The KEYNOTE-012 phase IB study is testing pembrolizumab for triple-negative breast cancer (TNBC), gastric cancer, urothelial cancer, and head and neck cancer.[15] It reported encouraging interim results (eg in TNBC) in 2016.[15] The ongoing phase II KEYNOTE-086 study is evaluating a 200-mg dose of pembrolizumab, given once every 3 weeks, in patients with TNBC.[15]

See also

External links

References

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  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ US 8952136  Antibodies to human programmed death receptor PD-1
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Amgen slaps record-breaking $178K price on rare leukemia drug Blincyto
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Press release, "Penn Medicine's New Immunotherapy Study Will Pit PD-1 Inhibitor Against Advanced Lung Cancer", University of Pennsylvania, February 4, 2015.
  15. ↑ 15.0 15.1 15.2 Keytruda Impresses in Triple-Negative Breast Cancer
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