Pembrolizumab
Monoclonal antibody | |
---|---|
Type | Whole antibody |
Source | Humanized (from mouse) |
Target | PD-1 |
Clinical data | |
Pregnancy category |
|
Legal status |
|
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
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ US 8952136 Antibodies to human programmed death receptor PD-1
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Amgen slaps record-breaking $178K price on rare leukemia drug Blincyto
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Lua error in package.lua at line 80: module 'strict' not found.
- ↑ Press release, "Penn Medicine's New Immunotherapy Study Will Pit PD-1 Inhibitor Against Advanced Lung Cancer", University of Pennsylvania, February 4, 2015.
- ↑ 15.0 15.1 15.2 Keytruda Impresses in Triple-Negative Breast Cancer
- Chemical articles having calculated molecular weight overwritten
- Drugs that are a monoclonal antibody
- Articles without EBI source
- Chemicals that do not have a ChemSpider ID assigned
- Articles without KEGG source
- Articles without InChI source
- Articles containing unverified chemical infoboxes
- Official website not in Wikidata
- Monoclonal antibodies for tumors
- Antineoplastic drugs
- Experimental cancer drugs
- Breakthrough therapy