Endoglin is upregulated following VEGF inhibition and may mediate resistance to pazopanib. A phase 1b/2a study of TRC105, an endoglin antibody, combined with pazopanib in patients with advanced soft-tissue sarcoma (STS) was reported at ASCO 2016. Based on activity in angiosarcoma (AS), additional patients with AS were recruited in an expansion cohort.
Phase 1b was a dose-escalation trial, whereas phase 2a was a single-arm evaluation of TRC105 10 mg/kg weekly with pazopanib 800 mg daily in STS. The AS expansion cohort (n = 13) included 2 groups: group A received TRC105 10 mg/kg with pazopanib 800 mg daily; group B received single-agent TRC105 10 mg/kg; pazopanib was added at progression.
Five patients with AS were treated in the original phase 1b/2a study. All demonstrated tumor reductions and 2 remain on study with durable complete response. Their median progression-free survival exceeded 13 months. Another 11 patients enrolled in the expansion cohort: 4 in group A, 7 in group B. In group A, 3 of 4 patients demonstrated tumor reduction; 2 remain on study. In group B, 4 of 7 patients added pazopanib following progression on TRC105; 5 remain on study.
A global phase 3 study of pazopanib ± TRC105 in patients with AS is planned.
Sankhala KK, et al. CTOS 2016. Abstract 2569989. P2 Poster 210.