unecritinib (investigational drug)

Action and Spectrum

Actions and Spectrum:  

Actions:  

A new crizotinib derivative, unecritinib inhibits numerous tyrosine kinases, including ALK, ROS1, and c-MET. It has been studied in Phase I/II trials for safety and efficacy in NSCLC with ROS1 rearrangement positive and advanced tumours. For patients with brain metastases and ROS1-positive NSCLC who have not yet received an inhibitor, it is highly helpful. 

Spectrum:  

It appears promising for both ALK-positive anaplastic large cell lymphoma cases & solid tumour research. 

Drug Interaction

Adverse Reaction

Frequency not defined  

Reduced neutrophil count  

Reduced WBC count  

Dysgeusia  

CNS abnormalities 

Dizziness  

Increased alanine aminotransferase  

Elevated AST and ALT levels 

Black Box Warning

Blackbox warning  

None 

Contraindication / Caution

Contraindication/Caution:  

Contraindications  

• Hypersensitivity  

Cautions  

• Kidney disease  
• Abnormalities of CNS 
• Low WBC count  
• Elevated AST & ALT 
• Hepatic impairment  

Pregnancy / Lactation

Pregnancy consideration:   

No data is available regarding the administration of the drug during pregnancy.  

Breastfeeding warnings:   

No data is available regarding the excretion of drug in breast milk.  

Pregnancy category:  

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester.  

<b>Category B: There was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.  

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: No data is available for the drug under this category.  

Pharmacology

Pharmacology:  

Unecritinib monotherapy is a possible first-line therapeutic option because of its optimistic efficacy outcomes and tolerable toxicity profile as the initial treatment for ROS1-positive NSCLC. 

Pharmacodynamics:  

Unecritinib is a derivative of crizotinib and is a multi-TKI that targets ALK, ROS1, and c-MET. In in vitro experiments, it inhibits ERK1/2 signalling and AKT phosphorylation.
On cancer cells with mutations, unecritinib has potent inhibitory effects, as seen by decreased IC50 and IC90 values in comparison to ROS1. 

Pharmacokinetics:  

Absorption  

Peak effect of the drug is achieved in 0.5-1 hour. 

Elimination and Excretion
The half-life of the drug is 4.6 hours. 

Adminstartion

Administration:  

The drug is taken orally. 

Patient Information Leaflet

Patient information leaflet  

Generic Name: unecritinib  

Pronounced: un-e-KRIT-i-nib  

Why do we use unecritinib?  

The drug unecritinib is beneficial for treatment of solid and advanced tumors. 

The drug is mainly used for non-small cell lung cancer.