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| Primary information |
|---|
| ID | 10839 |
| Therapeutic ID | Th1202 |
| Protein Name | Pembrolizumab |
| Sequence | >Th1202_Pembrolizumab
QVQLVQSGVEVKKPGASVKVSCKASGYTFTNYYMYWVRQAPGQGLEWMGGINPSNGGTNFNEKFKNRVTLTTDSSTTTAYMELKSLQFDDTAVYYCARRDYRFDMGFDYWGQGTTVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
|
| Molecular Weight | 149000 |
| Chemical Formula | C6504H10004N1716O2036S46 |
| Isoelectric Point | 6.8-6.9 |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | 22 days. |
| Description | Pembrolizumab is an antibody drug that targets the cell surface receptor programmed cell death protein 1 (PD-1) found on T cells. By preventing the binding of its ligands (PD-L1 and PD-L2), pembrolizumab induces an antitumor immune response. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Its use is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following therapy with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Due to its success in clinical trials, pembrolizumab was approved early to allow quick patient access and was given breakthrough therapy and orphan drug designation. Pembrolizumab (as Keytruda) was approved by the U.S. Food and Drug Administration to treat advanced cases of the most common type of lung malignancy, non-small cell lung cancer (NSCLC) on Oct. 2, 2015. |
| Indication/Disease | For the treatment of patients with unresectable or metastatic melanoma and disease progression following therapy with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. It is also for the treatment of patients with metastatic NSCLC (non-small cell lung cancer) whose tumors express PD-L1 (as determined by an approved test) and who have disease progression on or after platinum-containing chemotherapy. |
| Pharmacodynamics | In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth. |
| Mechanism of Action | Pembrolizumab is an antibody drug that targets the cell surface receptor programmed cell death protein 1 (PD-1) found on T cells. By preventing the binding of its ligands (PD-L1 and PD-L2), pembrolizumab induces an antitumor immune response. Upregulation of PD-1 ligands is a mechanism for tumours to evade antitumor immune response; when PD-1 binds its ligand, the T cell receives an inhibitory signal leading to T cell anergy and blockade of anti tumour immune response. Instead of directly targeting tumor tissue to induce tumor cell death, pembrolizumab acts as a checkpoint inhibitor to stimulate immune responses to eliminate cancer cells. |
| Toxicity | There are no data regarding overdosage with pembrolizumab. |
| Metabolism | Pembrolizumab is catalyzed into smaller peptides and amino acids via general protein degradation.[A18829] |
| Absorption | When administered intravenously, pembrolizumab is completely bioavailable. When administered in repeated doses every 3 weeks, the systemic accumulation accounts for a 2.2 fold increase.[A18829] Steady-state is reached after approximately 16 weeks.[L38934] The absorption of pembrolizumab increases proportionally with increased dosage.[L38934] |
| The steady-state volume of distribution of pembrolizumab is approximately 6 liters.[L38934] |
| Clearance | Clearance is moderately lower at steady-state (195 mL/day) than after the first dose (252 mL/day), although this decrease is not clinically significant.[L38934] |
| Categories | Amino Acids, Peptides, and Proteins,Antibodies,Antibodies, Monoclonal,Antibodies, Monoclonal, Humanized,Antineoplastic Agents,Antineoplastic Agents, Immunological,Antineoplastic and Immunomodulating Agents,Blood Proteins,Cancer immunotherapy,Globulins,Immune Checkpoint Inhibitors,Immunoglobulins,Immunoproteins,Immunotherapy,Programmed Death Receptor-1 Blocking Antibody,Programmed Death Receptor-1-directed Antibody Interactions,Proteins,Serum Globulins |
| Patents Number | US2012135408 |
| Date of Issue | 29-03-2012 |
| Date of Expiry | 29-03-2032 |
| Drug Interaction | NA |
| Target | Programmed cell death protein 1 |
| Brand Name | Keytruda |
| Company | Merck Sharp & Dohme Corp. |
| Brand Description | Merck Sharp & Dohme Corp. |
| Prescribed For | KEYTRUDA® (pembrolizumab) is indicated for the treatment of patients with unresectable or metastatic melanoma. |
| Chemical Name | NA |
| Formulation | 100 mg of pembrolizumab in 4 mL of solution. |
| Physical Appearance | lyophilized powder |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | The recommended dose of KEYTRUDA is 2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. |
| Contraindication | NA |
| Side Effects | Immune-mediated pneumonitis; Immune-mediated colitis; Immune-mediated hepatitis; Immune-mediated endocrinopathies; Immune-mediated nephritis and renal dysfunction; Other immune-mediated adverse reactions; Infusion-related reactions. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |