Drug Detail

Information about Cometriq

Generic Name
Cabozantinib
IND
XL-184
Brand Name (US)
Cometriq
Manufacturer
Exelixis
Drug Type
Delivery
Oral
Approval Status
Approved for a non-GIST cancer
Indications
Medullary thyroid cancer (advanced).
Overall Strategy
KIT Protein Based
Strategy
Block KIT + Block related tumor signal paths
Drug Category
KIT/PDGFRA inhibitor + MET/VEGF inhibitor

Cabozantinib is being developed as a c-MET (MET)/VEGF inhibitor, however it also inhibits KIT, AXL, FLT3 and TEK.
In a poster presented at 2013 CTOS, cabozantinib demostrated good activity in an imatinib-sensitive mouse model (xenograft). The conclusion of the abstract was:
"Cabozantinib as a single agent induced tumor regression, arrest of mitotic and proliferative activity, and inhibition of KIT signaling. Moreover, cabozantinib is more pro-apoptotic than single agent imatinib. Cabozantinib+ Imatinib combination induces a more significant reduction of tumor volume than either single agent treatment. The results warrant further testing of cabozantinib in other GIST xenografts (work ongoing), and exploration of the antitumor activity of cabozantinib in GIST patients failing established tyrosine kinase inhibitors." Based on this work, a clinical trial of cabozantinib for advanced GIST patients is being planned.
According to the Exelixes website, "Single-agent activity has been observed in several clinical trials, in diseases including medullary thyroid cancer, castration-resistant prostate cancer, lung cancer, and ovarian cancer. To date, we have observed objective responses in 12 of 13 tumor types studied and observed activity against metastatic bone lesions in five tumor types, including prostate, renal, breast, thyroid, and melanoma."
In a phase I trial of Japanese patients, 4 GIST patients that had been pre-treated with imatinib and sunitinib were included. All four had stable disease for at least 6 and up to 20 months.
Targets listed are based on the FDA prescribing information.


Links

 

Pharmacological inhibition of KIT activates MET signaling in gastrointestinal stromal tumors. (full text PDF available)
   

 

Full prescribing information (you must click "Full Prescribing Information" button at the top of this page)
   

 

Cabozantinib is active against human GIST xenografts carrying different KIT mutations.
   

 

FDA news release - FDA approves Cometriq to treat rare type of thyroid cancer
   

 

Phase 1 results in Japanese patients - A PHASE 1 STUDY OF CABOZANTINIB IN JAPANESE PATIENTS WITH ADVANCED SOLID TUMORS: ANTI-TUMOR ACTIVITY IN NSCLC AND GIST
   

 

Clinical use of cabozantinib in the treatment of advanced kidney cancer: efficacy, safety, and patient selection
   

 

A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors
   

 

XL-184, a MET, VEGFR-2 and RET kinase inhibitor for the treatment of thyroid cancer, glioblastoma multiforme and NSCLC
   

Trials of this drug

  

Ph II CABOGIST in GIST
   

  

Cabozantinib for Adults With Advanced Soft Tissue Sarcoma
   

  

Dose-Finding Study of Cabozantinib (XL184) in Japanese Subjects With Advanced Cancer
   

Trial results

  Cabozantinib induces promising response rate for soft tissue sarcoma CTOS 11/2017
   
  A PHASE 1 STUDY OF CABOZANTINIB IN JAPANESE PATIENTS WITH ADVANCED SOLID TUMORS: ANTI-TUMOR ACTIVITY IN NSCLC AND GIST
   
  A PHASE 1 STUDY OF CABOZANTINIB IN JAPANESE PATIENTS WITH ADVANCED SOLID TUMORS: ANTI-TUMOR ACTIVITY IN NSCLC AND GIST
   

Search for this drug/combination in:

ClinicalTrials.gov

ASCO

Pubmed