US-based Tracon Pharmaceuticals has started dosing patients in a multi-centre, open-label, non-randomised phase 1b dose-finding clinical trial evaluating the combination of TRC105 and Votrient (pazopanib), a vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, for the treatment of advanced soft tissue sarcoma.
TRC105 is a novel monoclonal antibody to endoglin (CD105) and is currently being studied in multiple clinical trials in combination with agents that target the VEGF pathway.
Endoglin is an endothelial cell receptor that is essential for the process of new blood vessel formation called angiogenesis.
TRACON president and CEO Charles Theuer said: "Preclinical and clinical data combining TRC105 with Avastin® support the hypothesis that endoglin mediates resistance to VEGF inhibitor treatment.
"Soft tissue sarcoma is an angiogenesis-driven tumor and certain sarcoma subtypes directly express endoglin on tumor cells.
"Combining TRC105 with Votrient has the potential to enhance activity by targeting both the tumor vasculature and the tumor itself.
"We look forward to working with our investigators in this study and building upon our clinical experience in combining TRC105 with agents that target the VEGF pathway."
The TRC105 development programme includes two ongoing randomised phase 2b studies with Avastin (bevacizumab) in renal cell carcinoma and glioblastoma, a combination study with Inlyta (axitinib) in renal cell carcinoma and a combination study with Nexavar (sorafenib) in hepatocellular carcinoma.
Currently, TRC105 is being studied in multiple clinical trials in cancer patients, sponsored by both TRACON and the National Cancer Institute (NCI) Cancer Therapy Evaluation Programme (CTEP), and is expected to complement VEGF inhibitor therapies (including Avastin).
It is also expected to complement VEGF inhibitor treatments in age-related macular degeneration.
Image: Optical Coherence Tomography (OCT) image of a sarcoma. Photo: courtesy of Oaktree b.