Prospective Study of Thrombospondin-1 Mimetic Peptides, ABT-510 and ABT-898, in Dogs with Soft Tissue Sarcoma

Background Exposure to anti-angiogenic thrombospondin-1 (TSP-1) mimetic peptides (MPs) has resulted in sporadic anti-tumor activity in humans and dogs. Hypothesis Novel TSP-1 MPs formulations will be safe, tolerated, and clinically active in soft tissue sarcoma (STS) in dogs. Animals Sixty-two client-owned dogs with measurable STS were enrolled, excluding hemangiosarcoma. Methods A prospective, single agent, multicenter, open-label study assessing ABT-510 bolus, ABT-898 bolus, or ABT-898 depot formulations of TSP-1 in dogs. Endpoints included tolerability, antitumor activity, and the assessment of ability of clinical covariates and circulating endothelial cells (CEC) concentration to predict tumor response. Results Two non-dose-limiting toxicoses possibly attributed to treatment were observed (keratitis and osteoarthritis). Antitumor activity (10/44=23% responses) was observed in study subjects who received treatment for >28days (n=44) including both partial (7) and minimal responses (3). Responses were disproportionately seen in dogs receiving ABT-898 formulations (9/28=32%) versus those receiving ABT-510 (1/16=6%; P<.045). Disease stabilization for >84days was also documented (8/44=18%). Slow rates of tumor progression before study entry correlated with anti-tumor activity in treated dogs, whereas no significant association was found between changes in total CEC concentration and tumor response (P=.28) or time to progression (P=.42). Conclusions and Clinical Importance Safely achieved antitumor activity was documented with TSP-1 MPs in dogs with STS. The most notable activity was achieved with the ABT-898 formulations.