amivantamab

Action and Spectrum

Actions and Spectrum 

Action: 

Targeting EGFR and MET: The drug is designed to simultaneously target two different proteins, epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET). Both EGFR and MET play significant roles in the growth and spread of cancer cells. 

Blocking signaling pathways: By binding to EGFR and MET, amivantamab inhibits their activation and downstream signaling pathways. This action helps to interrupt the signals that drive the proliferation, survival, and spread of cancer cells.  

Spectrum: The drug is primarily indicated for the treatment of patients with NSCLC who have specific genetic alterations. It is specifically approved for individuals who have: 

EGFR exon 20 insertion mutations (a specific type of EGFR mutation) and have progressed after platinum-based chemotherapy. 

Metastatic NSCLC with EGFR exon 20 insertion mutations as the only EGFR alteration. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

All grades 

Rash (84%) 

Increased ALT (38%) 

Paronychia (50%) 

Dyspnea (37%) 

Decrease albumin (79%) 

Musculoskeletal pain (47%) 

Increased glucose (56%) 

Increased creatinine (46%) 

Nausea (36%) 

Decreased lymphocytes (36%) 

Decreased phosphate (33%) 

Infusion-related reaction (64%) 

Increased alkaline phosphatase (53%) 

1-10% 

All grades 

Headache (10%) 

Pneumonia (10%) 

Grade 3 or 4 

Paronychia (3.1%) 

Decreased sodium (4%) 

Rash (3.9%) 

Increased GGT (4%) 

Increased alkaline phosphatase (4.8%) 

Decreased phosphate (8%) 

Decreased potassium (6%) 

Increased glucose (4%) 

Decreased albumin (8%) 

Diarrhea (3.1%) 

Decreased lymphocytes (8%) 

Increased GGT (4%) 

<1% 

Grade 3 or 4 

Dizziness (0.8%) 

Pneumonia (0.8%) 

Abdominal pain (0.8%) 

Edema (0.8%) 

Stomatitis (0.8%) 

Headache (0.8%) 

Black Box Warning

Black Box Warning: 

None

Contraindication / Caution

Contraindication/Caution:  

Hypersensitivity or Allergic Reactions: Patients who have experienced severe hypersensitivity reactions or allergic reactions to this drug or any of its components should not use the medication. 

Active Infections: If a patient has an active infection, especially a severe or systemic infection, treatment with this drug may be contraindicated.  

Pregnancy and Breastfeeding: Due to potential risks to the fetus or infant, it is generally advised to avoid its use during pregnancy or while breastfeeding. 

Immunosuppression: Patients who have compromised immune systems or are receiving immunosuppressive therapies may be at increased risk of infections. The use of this drug in these individuals may further suppress the immune system and increase the risk of infections.  

Severe Interstitial Lung Disease (ILD): If a patient has severe ILD or any other severe lung disease, the use of this drug may be contraindicated due to the potential risk of worsening lung function. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category  

Pharmacology

Pharmacology:  

The bispecific antibody drug under development is designed to effectively target two specific proteins, the epidermal growth factor receptor (EGFR) and the MET oncogene.  

Pharmacodynamics:  

The drug involves its ability to bind to both EGFR and MET simultaneously. This dual targeting mechanism is thought to be advantageous in overcoming resistance to EGFR tyrosine kinase inhibitors (TKIs) commonly seen in NSCLC patients with EGFR exon 20 insertion mutations. 

EGFR is a receptor tyrosine kinase that plays a critical role in regulating cell growth and survival. Mutations in the EGFR gene, including exon 20 insertions, can lead to constitutive activation of the receptor and the development of cancer. By binding to EGFR, amivantamab inhibits the signaling pathways that drive tumor growth and proliferation.  

Pharmacokinetics: 

Absorption 

The drug is administered intravenously (IV), meaning it is directly infused into the bloodstream. This route ensures rapid and complete absorption of the drug. 

Distribution 

After administration, The drug distributes throughout the body via the bloodstream. The specific distribution pattern and volume of distribution may vary based on factors such as body size, disease state, and individual patient characteristics. 

Metabolism 

The drug undergoes metabolic processes in the body. However, the detailed metabolic pathways and enzymes involved in its metabolism are not widely reported. 

Excretion and Elimination 

The elimination of the drug primarily occurs through clearance by the kidneys, which means it is excreted from the body through urine.

Adminstartion

Administration:  

The administration of drug is typically done through intravenous infusion. The exact dosing and treatment schedule may vary depending on the clinical trial protocol or the prescribing information if the drug gets approved.  

Typically, patients receive this drug once every two weeks, although this may change based on the specific trial or individual patient factors. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: amivantamab 

Why do we use amivantamab?   

Non-Small Cell Lung Cancer (NSCLC): The drug is primarily used in the treatment of advanced or metastatic NSCLC that harbors epidermal growth factor receptor (EGFR) exon 20 insertion mutations.   

Targeted Therapy: The drug is a targeted therapy that works by blocking signaling from EGFR and mesenchymal-epithelial transition (MET) receptors. By inhibiting these receptors, it can help inhibit tumor growth and survival in patients with NSCLC with EGFR exon 20 insertion mutations.  

Combination Therapy: The drug is often used in combination with another targeted therapy called lazertinib. The combination of amivantamab and lazertinib has shown promising results in clinical trials, providing improved efficacy in patients with EGFR-mutated NSCLC compared to either therapy alone.  

Treatment after Prior Therapies: It provides an additional treatment option for patients who have exhausted other available therapies.