Advanced Angiosarcoma Clinical Trial
Official title:
A Randomized Phase 3 Trial of TRC105 and Pazopanib Versus Pazopanib Alone in Patients With Advanced Angiosarcoma (TAPPAS)
This is a study of TRC105 in combination with standard dose pazopanib compared to single agent pazopanib in patients with angiosarcoma not amenable to curative intent surgery (e.g., metastatic or bulky disease, and disease for which surgical resection would carry an unacceptable risk to the patient) who have not received pazopanib or TRC105 previously.
TRC105 (carotuximab) is a monoclonal antibody to endoglin (CD105), an essential angiogenic
target highly expressed on tumor vessels that is distinct from VEGFR. Endoglin is also
expressed directly on tumor cells in angiosarcoma and is upregulated following VEGF
inhibition. TRC105 inhibits angiogenesis, tumor growth and metastases in preclinical models
and complements the activity of bevacizumab and multi-kinase inhibitors that target the
VEGFR.
Pazopanib is an oral inhibitor of multiple receptor tyrosine kinases, including vascular
endothelial growth factor receptor (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma
concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and
cancer progression.
By targeting a non-VEGF pathway that is upregulated following VEGF inhibition, TRC105 has the
potential to complement VEGFR tyrosine kinase inhibitors (TKIs) and could represent a major
advance in the treatment of angiosarcoma. Together, the use of TRC105 with pazopanib may
result in more effective angiogenesis inhibition and improved clinical efficacy over that
seen with pazopanib alone.
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