| Primary information |
|---|
| ThPP ID | Th1207 |
| Therapeutic Peptide/Protein Name | Necitumumab |
| Sequence | NA view full sequnce in fasta |
| Functional Classification | IIIc |
| Molecular Weight | 144800 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting Point (℃) | NA |
| Half Life | Approx 14 days |
| Description | Necitumumab is an intravenously administered recombinant monoclonal IgG1 antibody used in the treatment of non-small cell lung cancer (NSCLC) as an EGFR antagonist. It functions by binding to epidermal growth factor receptor (EGFR) and prevents binding of its ligands, a process that is involved in cell proliferation, metastasis, angiogenesis, and malignant progression. Binding of necitumumab to EGFR induces receptor internalization and degradation, thereby preventing further activation of EGFR which is beneficial in NSCLC as many patients have increased protein expression of EGFR. Necitumumab is approved for use in combination with cisplatin and gemcitabine as a first-line treatment for metastatic squamous non-small cell lung cancer (NSCLC). |
| Indication/Disease | Necitumumab is approved for use in combination with cisplatin and gemcitabine as a first-line treatment for metastatic squamous non-small cell lung cancer (NSCLC). It is not indicated for treatment of non-squamous NSCLC. |
| Pharmacodynamics | In animal models administration of necitumumab to implanted mice resulted in increased antitumor activity in combination with gemcitabine and cisplatin as compared to mice receiving gemcitabine and cisplatin alone. |
| Mechanism of Action | Necitumumab is a recombinant human lgG1 monoclonal antibody that binds to the human epidermal growth factor receptor (EGFR) and blocks the binding of EGFR to its ligands. Expression and activation of EGFR has been correlated with malignant progression, induction of angiogenesis, and inhibition of apoptosis. Binding of necitumumab induces EGFR internalization and degradation in vitro. In vitro, binding of necitumumab also led to antibody-dependent cellular cytotoxicity (ADCC) in EGFR-expressing cells. |
| Toxicity | 6 cycles showed the absence of disease progression or unacceptable toxicity. |
| Metabolism | NA |
| Absorption | NA |
| Volume of Distribution | Steady state volume of distribution (Vss) is 7.0 L |
| Clearance | Mean total systemic clearance (CLtot) at steady state is 14.1 mL/h |
| Categories | NA |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | NA |
| Information of corresponding available drug in the market |
|---|
| Brand Name | Portrazza |
| Company | Eli Lilly and Company |
| Brand Discription | Necitumumab is an anti-EGFR recombinant human monoclonal antibody of the IgG1 kappa isotype that specifically binds to the ligand binding site of the human EGFR. |
| Prescribed for | PORTRAZZAâ„¢ is indicated, in combination with gemcitabine and cisplatin, for first-line treatment of patients with metastatic squamous non-small cell lung cancer. |
| Chemical Name | NA |
| Formulation | Each vial contains 800 mg PORTRAZZA in 50 mL (16 mg/mL) |
| Physcial Appearnce | Sterile, preservative free, clear to slightly opalescent and colorless to slightly yellow solution |
| Route of Administration | intravenous |
| Recommended Dosage | The recommended dose of PORTRAZZA is 800 mg administered as an intravenous infusion over 60 minutes on Days 1 and 8 of each 3-week cycle prior to gemcitabine and cisplatin infusion. Continue PORTRAZZA until disease progression or unacceptable toxicity. |
| Contraindication | NA |
| Side Effects | Cardiopulmonary Arrest; Hypomagnesemia; Venous and Arterial Thromboembolic Events; Dermatologic Toxicities; nfusion-Related Reactions; Non-Squamous NSCLC - Increased Toxicity and Increased Mortality . |
| Useful Link | http://www.rxlist.com/portrazza-drug/side-effects-interactions.htm |
| PubMed ID | 28293124, 28277882, 28111429, 27913776, 27912834, 27628194, 27575423, 27729681, 27696220 |
| 3-D Structure | N.A. |