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.