Abstract 5390: QBI-139, a human RNase variant in a phase I trial, works in combination

Abstract

Abstract The EVade™ Ribonucleases (RNases) are a new class of anti-cancer drugs that target the RNA in cancer cells. These EVade™ RNases are variants of native mammalian RNases that have been converted to anti-cancer agents by diminishing their binding to their natural inhibitor protein. One of these EVade™ RNases, called QBI-139, has advanced to human clinical trials. QBI-139 shares 95% sequence identity with the wild type human RNase 1. QBI-139 has shown tumor growth inhibition against a variety of cancers, including: colon, non-small cell lung, ovarian, pancreatic and prostate cancers. QBI-139 is currently in a Phase I clinical trial in patients with solid tumors. A frog RNase called Ranpirnase (Alfacell) that shares only 20% sequence identity with human RNase 1 has been in clinical trials and responses have been seen in esophageal, non-small cell lung and breast cancers as well as unresectable mesothelioma. The next stage of clinical development of QBI-139 will require selection of a specific indication as well as an existing treatment regimen to be used in combination with QBI-139. The Phase I trial may provide insights about sensitive tumor types. However, mouse models of cancer will be used to select the combinations for development. QBI-139 has shown efficacy against non-small cell lung cancer (A549 cell line) in xenograft models. Cisplatin is a standard of care treatment for non-small cell lung cancer in patients. The ability of QBI-139 and cisplatin to work together to cause tumor growth inhibition was determined in a non-small cell lung cancer xenograft model (A549 cell line). Cisplatin (3 mg/kg) and QBI-139 (15 mg/kg) were used as controls. The combination of cisplatin and QBI-139 (3 and 15 mg/kg, respectively) was also tested. Cisplatin treatment resulted in tumor growth inhibition (TGI) of 60% while QBI-139 caused 76% TGI. The combination of the two drugs resulted in a TGI of 96%, strongly supporting the use of QBI-139 in combination with cisplatin for the treatment of lung cancer. Even the combination of the two drugs exhibited minimal impact on the health of the animals. EVade™ Ribonucleases are novel agents that provide a new way to target the RNA in cancer cells and are an innovative new tool for oncologists. QBI-139 has a variety of benefits, including: a novel mechanism of action with clinical support, broad in vivo anti-tumor activity alone and in combination with standard of care therapies and a strong tolerability profile. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5390.