Phase I expansion trial of an oral TORC1/TORC2 inhibitor (CC-223) in diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM).

8522 Background: CC-223 is an ATP-competitive inhibitor of the mTOR kinase, including both TORC1 and TORC2 complexes. CC-223 was selected to address resistance of rapamycin analogues mediated by TORC2 activation. Methods: Following establishment of the MTD (reported at ASCO 2012), subjects with advanced DLBCL, MM and select solid tumors were enrolled in parallel expansion cohorts of up to 20 evaluable subjects. CC-223 was dosed at 45 mg once daily in 28 day cycles until disease progression. Results: As of 09 January, 2013, 35 subjects were enrolled including DLBCL (21) and MM (14). Results in solid tumor cohorts are reported separately. The most common (> 20%) related adverse events (all grades) were fatigue, hyperglycemia, rash, anorexia, nausea, vomiting and diarrhea. In addition, related serious adverse events included infection (2), pneumonitis (1), renal insufficiency (2), pancreatitis (1) and thrombocytopenia (1). CC-223 dose reduction was required in 9 subjects (27%), usually during cycle 1 or 2, a...