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| Primary information |
|---|
| ID | 12548 |
| Therapeutic ID | Th1332 |
| Protein Name | Olaratumab |
| Sequence | >Th1332_Olaratumab
QLQLQESGPGLVKPSETLSLTCTVSGGSINSSSYYWGWLRQSPGKGLEWIGSFFYTGSTYYNPSLRSRLTISVDTSKNQFSLMLSSVTAADTAVYYCARQSTYYYGSGNYYGWFDRWDQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
|
| Molecular Weight | 154000 |
| Chemical Formula | C6554H10076N1736O2048S40 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Estimated value of 11 days |
| Description | Olaratumab (IMC-3G3) is a fully human IgG1 monoclonal antibody with antitumor activity that selectively binds the external domain of human platelet-derived growth factor receptor (PDGFR)-a with high affinity and blocks ligand binding. It is composed of two heavy chain molecule fragments and 2 light chain fragments. Studies show that the treatment of olaratumab in combination with doxorubicin resulted in significant reduction of cancer cell proliferation and tumor growth. Olaratumab was granted accelerated approval (as Lartruvo) as initial therapy to treat adults with certain types of soft tissue sarcoma (STS) in October, 2016. |
| Indication/Disease | Olaratumab is indicated, in combination with doxorubicin, for the treatment of adult patients with advanced or mestastatic soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery. |
| Pharmacodynamics | It exerts an anti-tumor activity in vivo and in vitro against selected sarcoma cells by inhibiting tumor growth by binding to PDGFR-alpha that is present on several types of cancer on transformed cells and in tumor stroma [A18695]. Olaratumab antibody binding leads to inhibition of ligand-dependent signaling in PDGFR(alpha)-expressing tumor cells, as well as stromal cells in the tumor microenviroment that are dependent on PDGFR(alpha) signaling. When used in a combination therapy with doxorubicin, olaratumab improves progression-free survival in patients with advanced soft-tissue sarcoma. |
| Mechanism of Action | Olaratumab blocks ligand-induced tumor cell proliferation, and inhibits receptor autophosphorylation and ligand-induced phosphorylation of the downstream signaling molecules protein kinase B (Akt) and mitogen-activated protein kinase [A19171]. PDGFR signalling is a type of tyrosine kinase-mediated pathway that normally regulates cell growth, chemotaxis, and mesenchymal stem cell differentiation. It also promotes internalization of PDGFR thus alters the surface levels of PDGFR. |
| Toxicity | Infusion-related reactions may occur during or after the administration which include bronchospasm, flushing, hypotension, anaphylactic shock, or cardiac arrest. Olaratumab may cause embryo-fetal toxicity based on animal data and its mechanism of action. Other reported adverse effects include neutropenia, leukopenia, anemia, nausea and musculoskeletal pain. |
| Metabolism | Mainly degraded nonspecifically by proteolytic enzymes |
| Absorption | NA |
| 7.7 L at steady state. |
| Clearance | Mean value of 0.56L/day |
| Categories | Antineoplastic Agents |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Platelet-derived growth factor receptor alpha |
| Brand Name | Lartruvo |
| Company | Eli Lilly & Co. Ltd. |
| Brand Description | Eli Lilly & Co. Ltd. |
| Prescribed For | Intravenous |
| Chemical Name | 190 mg / 19 mL |
| Formulation | None. |
| Physical Appearance | nausea, fatigue, musculoskeletal pain, inflammation of the mucous membranes in the digestive tract (mucositis), hair loss, vomiting, diarrhea, decreased appetite, abdominal pain, numbness and tingling, headache, fatigue, infusion-related reactions, anxiety, dry eyes, and lab abnormalities (lymphopenia, neutropenia, thrombocytopenia, hyperglycemia, elevated aPTT, hypokalemia, and hypophosphatemia). |
| Route of Administration | Olaratumab is a recombinant human IgG1 monoclonal blocking antibody that binds specifically to human plateletderived growth factor receptor alpha (PDGFR-α). LARTRUVO has an approximate molecular weight of 154 kDa. LARTRUVO is produced in genetically engineered mammalian NS0 cells. |
| Recommended Dosage | LARTRUVO™ is indicated, in combination with doxorubicin, for the treatment of adult patients with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |