Abstract 1568: GLPG0187, a small molecule integrin antagonist, shows good safety and decrease in CTX levels in single ascending dose study

Introduction : GLPG0187, a small molecule integrin antagonist with nanomolar affinity for the RGD-integrin receptors αvβ1, αvβ3, αvβ5, αvβ6 and α5β1, shows potent anti-angiogenic, anti-metastatic, anti-bone-resorption and anti-tumor activity in vitro and in vivo. Therefore GLPG0187 may offer a promising therapeutic approach for the treatment of integrin receptor expressing tumors and/or metastases. Methods: Based on promising preclinical data, a first-in-human study was performed with GLPG0187 to assess the safety and tolerability as well as pharmacokinetic and pharmacodynamic behavior of single ascending doses of the compound. GLPG0187 was administered subcutaneously in a dose range of 17.5 to 315 mg and orally in a dose range of 50 to 1200 mg. Results: GLPG0187 was systemically well tolerated with no adverse effects on ECG, vital signs or laboratory parameters. GLPG0187 showed a dose proportional pharmacokinetic profile over the dose range tested. Moreover, GLPG0187 dose proportionally decreased osteoclast activity as measured by plasma CTX (carboxy-terminal collagen crosslinks) levels. Conclusions: GLPG0187 was shown to be safe and well tolerated, to have a dose proportional pharmacokinetics and to inhibit osteoclast activity. These results provide further evidence that GLPG0187 could be an effective therapeutic for the treatment of cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1568.