UNASSIGNED: The inhibitor of apoptosis (IAP) family of antiapoptotic proteins has been identified as a target for small molecule inhibitors in @entity5 . @entity17205 ( @entity17205 ) efficiently and naturally antagonizes IAPs, and preclinical studies have determined that @entity17205 mimetics have potent anticancer properties. Here, we report a first-in- @entity1 trial designed to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics/pharmacodynamics (PK/ @entity1726 ) of birinapant, a novel @entity17205 mimetic. @entity1 with advanced solid @entity5 or @entity706 were enrolled in a 3+3 dose escalation design with birinapant administered intravenously from 0.18 to 63 mg/m(2) once weekly every 3 of 4 weeks. Fifty @entity1 were enrolled to 12 dose cohorts. Birinapant 47 mg/m(2) was determined to be the MTD. At 63 mg/m(2), dose-limiting @entity137 included @entity10 , @entity390 , and @entity391 . Two cases of @entity4401 (grade 2) also occurred at 63 mg/m(2). Birinapant had a plasma half-life of 30 to 35 hours and accumulated in @entity5 tissue. Birinapant suppressed @entity1839 and increased apoptosis in peripheral blood mononuclear cells and @entity5 tissue. @entity1162 was observed in 3 @entity1 : @entity1149 (5 months), @entity14 (5 months), and @entity1821 (9 months). Two @entity1 with @entity14 had radiographic evidence of @entity5 shrinkage. In conclusion, birinapant was well tolerated with an MTD of 47 mg/m(2) and exhibited favorable PK and @entity1726 properties. Several @entity1 demonstrated stable disease and evidence of antitumor activity. These results support the ongoing clinical trials of birinapant in @entity1 with @entity5 . Mol Cancer Ther; 14(11); 1-7.   2015 AACR.

A Phase I Study of the XXXX -Mimetic Birinapant in Adults with Refractory Solid Tumors or @entity706 .

@entity1 :: ('9606', 'Species') :: ['Patients', 'human', 'patients'] @entity17205 :: ('56616', 'Gene') :: ['Second mitochondrial-derived activator of caspases', 'SMAC'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicities'] @entity390 :: ('MESH:D009325', 'Disease') :: ['nausea'] @entity706 :: ('MESH:D008223', 'Disease') :: ['lymphoma'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors', 'cancer'] @entity391 :: ('MESH:D014839', 'Disease') :: ['vomiting'] @entity4401 :: ('MESH:D020330', 'Disease') :: ["Bell's palsy"] @entity1149 :: ('MESH:D002289', 'Disease') :: ['non-small cell lung cancer'] @entity1839 :: ('329', 'Gene') :: ['cIAP1'] @entity1726 :: ('OMIM:168600', 'Disease') :: ['PD'] @entity14 :: ('MESH:D015179', 'Disease') :: ['colorectal cancer'] @entity1162 :: ('MESH:D008133', 'Disease') :: ['Prolonged stable disease'] @entity10 :: ('MESH:D006261', 'Disease') :: ['headache'] @entity1821 :: ('MESH:D008080', 'Disease') :: ['liposarcoma']
@entity17205 :: (56616,Gene) :: ['SMAC']
